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Under saline conditions, Suaeda salsa, as a typical halophyte, accumulates large amounts of Na+ in its leaves during optimal growth. Key transporters involved in Na+ accumulation in plants are HKT-type protein, the plasma membrane Na+/H+ transporter SOS1, and the tonoplast Na+/H+ antiporter NHX1. In this study, the function of SsHKT1;1 and its coordinate expression with SsSOS1 and SsNHX1 to regulate Na+ homeostasis in S. salsa was investigated. We showed, by yeast complementation assays, that SsHKT1;1 encoded a Na+-selective transporter, which located to the plasma membrane and was preferentially expressed within the stele, and was particularly abundant in xylem parenchyma and pericycle cells. When compared with a treatment of 25 mM NaCl, 150 mM NaCl greatly decreased the transcripts of SsHKT1;1, but maintained a relatively constant level of the expression of SsSOS1 in roots. Consequently, the synergistic effect of SsHKT1;1 and SsSOS1 would result in greater Na+ loading into the xylem under 150 mM NaCl than 25 mM NaCl. In leaves, 150 mM NaCl up-regulated the abundance of SsNHX1 compared with levels in 25 mM NaCl. This enabled the permanent sequestering of Na+ into leaf vacuoles. Overall, SsHKT1;1 functioned in reducing Na+ retrieval from the root xylem, and played an important role in coordinating with SsSOS1 and SsNHX1 to maintain Na+ accumulation in S. salsa under saline conditions.

In this study, methanofullerenes and 2′,3′-dihydrofuran C60 derivatives were selectively synthesized in high yields via the reactions of C60 with β-keto esters under mild conditions by controlling the addition sequence and molar ratio of iodine and base. The structures of the products were determined by spectroscopic characterization. Moreover, a possible reaction mechanism for the selective formation of fullerene derivatives was proposed.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Secretory leukocyte protease inhibitor (SLPI) has been reported to function as a regulatory factor in several cancers. However, its biological functions and underlying mechanisms in HCC remain to be uncovered. Here, we aimed to explore the effect of SLPI in HCC. In our study, we found that the mRNA and protein expression levels of SLPI were significantly down-regulated in HCC tissues and hepatoma cell lines and low level of SLPI predicted worse survival in our HCC cohorts. In term of function, silencing of SLPI markedly promoted whereas overexpression SLPI suppressed proliferation, migration and invasion capabilities of HCC cells in vitro, and ectopic expression of SLPI inhibited the tumorigenicity of HCC cells in vivo. Mechanistic studies demonstrated that SLPI played a protective role in HCC progression via activating endoplasmic reticulum stress (ER stress)-mediated apoptosis of hepatoma cells, which could be regulated by MAPK signaling pathways. In summary, our findings highlight that SLPI could serve as a potential prognostic biomarker and putative tumor suppressor by enhancing ER stress-induced apoptosis in HCC cells mediated by MAPK signaling pathways, which provides new insights into promising therapeutic targets for HCC treatment.

α-Glucosidase is a promising target for the treatment of diabetes. Drug repurposing can increase the chances of discovering an active inhibitor. Therefore, this study aimed to identify potential α-glucosidase inhibitor using drug repurposing and in silico strategies. We identified critical amino acid residues of the three α-glucosidase proteins. Based on cross molecular docking studies of three α-glucosidase proteins and drugs in the FDA database, we screened hits with the favorable binding affinities and modes targeting the three proteins. Subsequently, an in vitro activity assay showed that raloxifene was an excellent inhibitor of α-glucosidase. Moreover, molecular dynamics simulations of raloxifene and three proteins were performed to assess the stability of the protein-hit systems in physiological conditions and clarify protein-hit interactions. We also performed the binding free energy calculation, Hirshfeld surface and alanine scanning mutagenesis analyses. These results demonstrated that binding between raloxifene and the three proteins was stable, and the critical amino acid residues of the three proteins formed stable contacts with raloxifene. The molecular mechanisms agree well with its activity, reinforcing that raloxifene is a candidate α-glucosidase inhibitor. Our study smoothes the path for the development of novel a-glucosidase inhibitors with high efficacy and low toxicity for the treatment of diabetes.

Background To understand the gene expression networks controlling flower color formation in alfalfa, flowers anthocyanins were identified using two materials with contrasting flower colors, namely Defu and Zhongtian No. 3, and transcriptome analyses of PacBio full-length sequencing combined with RNA sequencing were performed, across four flower developmental stages. Results Malvidin and petunidin glycoside derivatives were the major anthocyanins in the flowers of Defu, which were lacking in the flowers of Zhongtian No. 3. The two transcriptomic datasets provided a comprehensive and systems-level view on the dynamic gene expression networks underpinning alfalfa flower color formation. By weighted gene coexpression network analyses, we identified candidate genes and hub genes from the modules closely related to floral developmental stages. PAL, 4CL, CHS, CHR, F3’H, DFR, and UFGT were enriched in the important modules. Additionally, PAL6, PAL9, 4CL18, CHS2, 4 and 8 were identified as hub genes. Thus, a hypothesis explaining the lack of purple color in the flower of Zhongtian No. 3 was proposed. Conclusions These analyses identified a large number of potential key regulators controlling flower color pigmentation, thereby providing new insights into the molecular networks underlying alfalfa flower development.

Objective The goal of this meta-analysis was to determine whether the serum levels of C-reactive protein (CRP) and creatine kinase-MB (CK-MB) are correlated with the severity of hand-foot-and-mouth disease (HFMD). Methods We conducted a systematic search and meta-analysis of the MEDLINE, PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, VIP information, and Wanfang Chinese Periodical databases. The analysis included all published case–control, cohort, and cross-sectional studies of serum CRP and/or CK-MB levels in children with HFMD up to December 4, 2014. Pooled estimates were calculated using a random-effects model or a fixed-effects model. Results Thirty-eight articles are included in this meta-analysis. The summary estimates revealed that the average serum CRP levels, prevalence of high CRP, average serum CK-MB levels, and prevalence of high CK-MB increased with the severity of HFMD. There were no significant differences in the average levels of serum CK-MB (pooled MD = 22.29 U/L; 95% CI: −0.82–45.39 U/L, P = 0.06) between patients who were critically ill and those with severe HFMD. Therefore, we compared the average levels of serum CRP (pooled MD = 1.17 mg/L; 95% CI: −0.88–3.21 mg/L, P = 0.26) between patients infected with enterovirus 71 and those infected with coxsackievirus A16. Conclusions The result of these analyses indicated that the CRP and CK-MB levels are correlated with HFMD severity. Thus, these frequently used and accessible measures may aid clinicians in effectively diagnosing, treating, and predicting the prognosis of children with HFMD.

The Shaker AKT1-like channels are considered to be involved in both high- and low-affinity K+ uptake and correlated with salt tolerance in glycophytes. Suaeda salsa (Suaeda maritima subsp. salsa), as a typical salt-accumulating halophyte, is able to absorb K+ efficiently while growing under saline conditions and taking in a large amount of Na+, thus maintaining the K+ concentration in its cells. In this study, the possible functions of the inward-rectifying K+ channel SsAKT1 in K+ uptake and salt tolerance in the halophyte S. salsa were investigated. SsAKT1 from S. salsa was isolated by RT-PCR and characterized using yeast complementation; the responses of SsAKT1 to various KCl and NaCl treatments were investigated by real-time quantitative PCR. SsAKT1 consisted of 879 amino acid residues and shared high homology (60–67 %) with the identified inward-rectifying K+ channels AKT1 from other plants. The expression of SsAKT1 rescued the K+-uptake-defective phenotype of yeast strain CY162, and also suppressed the salt-sensitive phenotype of yeast strain G19, suggesting SsAKT1 functioned as an inward-rectifying K+ channel. SsAKT1 was predominantly expressed in roots, and was induced significantly by K+ starvation; transcript levels increased further on resupply of K+ (0.1–10 mM for 6 h) by 62 % in 0.1 mM K+ and 144–174 % in higher K+ concentrations (1–10 mM). Interestingly, the expression level of SsAKT1 in roots was also induced significantly by short-term treatment (6 h) with NaCl concentrations (25–250 mM). These results demonstrate that the inward-rectifying K+ channel SsAKT1 might mediate both high- and low-affinity K+ uptake in S. salsa, but play a greater role in the low-affinity system. Furthermore, SsAKT1 might also be involved in salt tolerance by participating in the maintenance of K+ nutrition in S. salsa under salinity.

Cytokines, including receptor activator of nuclear factor κB ligand (RANKL) and TNF, induce increased osteoclast (OC) formation and bone loss in postmenopausal osteoporosis and inflammatory arthritides. RANKL and TNF can independently induce OC formation in vitro from WT OC precursors via TNF receptor-associated factor (TRAF) adaptor proteins, which bind to their receptors. Of these, only TRAF6 is required for RANKL-induced osteoclastogenesis in vitro. However, the molecular mechanisms involved remain incompletely understood. Here we report that RANKL induced the formation of bone-resorbing OCs from TRAF6−/− OC precursors when cultured on bone slices but not on plastic. The mechanisms involved increased TNF production by TRAF6−/− OC precursors resulting from their interaction with bone matrix and release of active TGFβ from the resorbed bone, coupled with RANKL-induced autophagolysosomal degradation of TRAF3, a known inhibitor of OC formation. Consistent with these findings, RANKL enhanced TNF-induced OC formation from TRAF6−/− OC precursors. Moreover, TNF induced significantly more OCs from mice with TRAF3 conditionally deleted in myeloid lineage cells, and it did not inhibit RANKL-induced OC formation from these cells. TRAF6−/− OC precursors that overexpressed TRAF3 or were treated with the autophagolysosome inhibitor chloroquine formed significantly fewer OCs in response to TNF alone or in combination with RANKL. We conclude that RANKL can enhance TNF-induced OC formation independently of TRAF6 by degrading TRAF3. These findings suggest that preventing TRAF3 degradation with drugs like chloroquine could reduce excessive OC formation in diseases in which bone resorption is increased in response to elevated production of these cytokines.

A series of novel Schiff base-bridged tetrahydroprotoberberine (THPB) triazoles were designed, synthesized and characterized for the first time. Antimicrobial assay showed that some of the prepared compounds exerted stronger antibacterial and antifungal activities than the reference drugs. Especially, THPB triazole 7a gave low MIC values of 0.5, 1 and 2 μg mL−1 against B. yeast, M. luteus and MRSA, respectively. Further experiments indicated that the highly active molecule 7a was able to rapidly kill the MRSA strain and did not trigger the development of bacterial resistance even after 14 passages. The preliminary exploration for the antimicrobial mechanism revealed that compound 7a could effectively intercalate into calf thymus DNA to form a 7a–DNA supramolecular complex, and its Zn2+ complex had the ability to directly cleave pUC19 DNA, which suggested that compound 7a might be a potentially dual-targeting antibacterial molecule. It was also found that compound 7a could be efficiently stored and carried by human serum albumin (HSA), and the hydrophobic interactions and hydrogen bonds played important roles in the transportation of HSA to the active molecule 7a.

A new method to prepare polysaccharide-coating type chiral stationary phases (CSPs) was developed in this work. As a typical example, naked silica gel was coated by cellulose, which was then derivatized with 3,5-dimethylbenzoyl chloride to afford cellulose tris(3,5-dimethylbenzoate)-silica gel (CTDBS) complex. The silanols on CTDBS were end-capped with 3-aminopropyltriethoxysilane to obtain CSP 1. The amino groups on CSP 1 were further end-capped with 3,5-dimethylbenzoyl chloride to give CSP 2. The silanols on CTDBS were end-capped with methyltrimethoxysilane to yield CSP 3. CSPs 1–3 were characterized by FTIR, solid-state 13C-NMR and elemental analysis. The enantioseparation abilities of CSPs 1–3 were evaluated with structurally various chiral analytes. The enantioseparation results demonstrated that the end-capping moieties on CSPs 1 and 2 significantly affected enantioseparation. In addition, the effect of the structures of chiral analytes and endcapping moieties on the retention factors and the resolutions was discussed.

The effects of nanometer calcium carbonate content and tensile rate on the tensile properties of the filled polycaprolactone (PCL) composites were investigated. There was a certain reinforcing effect of the filler on the PCL resin. The tensile modulus increased nonlinearly, and the tensile strength also increased with increase of the filler weight fraction. When the filler weight fraction was kept constant, the tensile modulus and tensile strength increased slightly with increasing tensile rates. By comparing the experimental results with those determined from the tensile yield strength theory, the interfacial adhesion between the filler and matrix was found to be relatively strong; it should be one of the reasons for the good reinforcing effect.

The tensile properties of poly ( l -lactic acid) (PLLA) and polycaprolactone (PCL) composites filled with nanometer calcium carbonate (nano-CaCO3) were measured at room temperature and different tensile rates. With increase of the PCL weight fraction, the tensile elastic modulus, tensile strength and tensile strength at fracture for the PLLA/PCL/nano-CaCO3 composites decreased nonlinearly, and it increased slightly with increasing tensile rate. When the PCL weight fraction was less than 60%, the elongation at break for the composites increased slightly and then it increased sharply. This indicated that PCL was beneficial to improve the tensile fracture toughness of the composites.

The flexural properties of poly-L-lactide (PLLA) and polycaprolactone (PCL) shape memory composites filled with nanometer calcium carbonate (nano-CaCO3) were determined at room temperature. The results showed that with the increase of the nano-CaCO3 weight fraction the flexural moduli and strength of PCL/nano-CaCO3 composites increased roughly linearly and reached a maximum at the filler content of 2%, while the flexural strength of the composites decreased. The flexural moduli and strength of the composites decreased roughly linearly with increasing PLLA/PCL ratio for the PLLA/PCL/nano-CaCO3 composites.

// Jing Ma 1, 2, 3, * , Ming Shen 4, * , Chang Song Xu 5, * , Ying Sun 4 , You Rong Duan 4 , Lian Fang Du 2 1 Department of Ultrasound, Songjiang Hospital Affiliated to The First People’s Hospital of Shanghai Jiao tong University, Shanghai 201600, China 2 Department of Ultrasound, Shanghai First People’s Hospital Affiliated to Shanghai Jiao tong University School of Medicine, Shanghai 200080, China 3 Department of Ultrasound, Shanghai East Hospital Affiliated to Tong ji University, Shanghai 200120, China 4 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, P. R. China 5 Huai’an First People’s Hospital, Nanjing Medical University, Jiangsu 223001, China * These authors have contributed equally to this work Correspondence to: Lian Fang Du, email: du_lf@163.com You Rong Duan, email: yrduan@shsci.org Keywords: double-targeted, nanoparticles, antitumor, ultrasound contrast enhanced imaging, pancreatic cancer Received: July 25, 2016 Accepted: October 19, 2016 Published: November 09, 2016 ABSTRACT A porous-structure nano-scale ultrasound contrast agent (UCA) was made of monomethoxypoly (ethylene glycol)-poly (lactic-co-glycolic acid) (mPEG-PLGA), and modified by double-targeted antibody: anti-carcinoembryonic antigen (CEA) and anti-carbohydrate antigen 19-9 (CA19-9), as a double-targeted nanoparticles (NPs). Anti-tumor drug paclitaxel (PTX) was encapsulated in the double-targeted nanoparticles (NPs). The morphor and release curve were characterized. We verified a certain anticancer effect of PTX-NPs through cytotoxicity experiments. The cell uptake result showed much more NPs may be facilitated to ingress the cells or tissues with ultrasound (US) or ultrasound targeted microbubble destruction (UTMD) transient sonoporation in vitro . Ultrasound contrast-enhanced images in vitro and in vivo were investigated. Compared with SonoVue, the NPs prolonged imaging time in rabbit kidneys and tumor of nude mice, which make it possible to further enhance anti-tumor effects by extending retention time in the tumor region. The novel double-targeted NPs with the function of ultrasound contrast enhanced imaging and anti-tumor therapy can be a promising way in clinic.

An organic-based monolith with long alkyl chain ligands was prepared by UV photo-initiation using (a) 1-octadecene as a functional monomer, (b) ethylene glycol dimethacrylate (EDMA) as the cross-linking agent, (c) 1-propanol, 1,4-butanediol and dimethylformamide as triporogenic solvents, and (d) Irgacure 1800 as the initiator. The monoliths containing a high fraction of 1-octadecene possessed a better total porosity, improved permeability, and result in faster separation. Similar monolithic capillary was quickly fabricated in 3 min by microwave irradiation using azobisisobutyronitrile as the thermal initiator. Conventional polyimide-coated capillaries were used instead of expensive UV-transparent capillaries in both methods.

Comb-shaped hyper-branched polycarboxylate polymers, both water-reducing-type admixtures (applied in cement, symbol of JS) and slump-retaining-type admixtures (applied in cement, symbol of BT), were prepared, and their adsorption characteristics with SO42- ions were studied by conductivity loss experiments. The results indicated that both JS and BT generate electrical conductivity losses in Na2SO4 aqueous solutions, suggesting that there was some interaction adsorption between the SO42- ions and the polymer. The adsorption was closely related to the pH of the sample solutions and occurred due to the strong interactions between the carboxylic acid groups in the polymer backbones and SO42- ions (rather than Na+ ions). However, there was an extremely weak electrostatic adsorptive interaction between the SO42- ions and the long polyether side-chain.

Comb-shaped hyper-branched polycarboxylate admixture polymers, both the water-reducing-type JS and slump-retaining-type BT, were prepared, and their adsorption characteristics with Ca2+ions were studied by conductivity loss experiments. The results indicated that, both the water-reducing-type JS and slump-retaining-type BT, would generate certain electrical conductivity loss in CaCl2aqueous solutions, suggesting that there was some close adsorption between the polymer and Ca2+ions, the adsorption was closely related with the pH value of the polymers, the neutral and alkaline samples neutralized by NaOH show an higher adsorption than that non-neutralized. The adsorption was achieved by the strong interaction between carboxylic acid groups in the polymer backbones and Ca2+ions (rather than Cl-ions)

Comb-shaped hyper-branched polycarboxylate admixture polymers, both the water-reducing-type JS and slump-retaining-type BT, were prepared, and their adsorption characteristics with SO42- ions were studied by conductivity loss experiments. The results indicated that the adsorptions were related to both the content of carboxylic acid groups in polymers and the concentration of Na2SO4 solution, adsorptive action was formed by the complexation action between the carboxylic acid groups in polymers and SO42- ions, having nothing to do with polyether side chain in polymer. Comb-shaped hyper-branched polymers in aqueous solution would form association super-molecular structure, which could be destroyed by Na2SO4 solution.

Background A novel small interfering RNA (siRNA) delivery method based on the combined use of nanoparticles (NPs) with ultrasound (US) and/or microbubbles (MBs) was introduced in the present study. We investigated the efficacy and safety of US and/or MBs-enhanced delivery of monomethoxypoly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly l-lysine (mPEG-PLGA-PLL) NPs loading platelet-derived growth factor BB (PDGF-BB) siRNA to rat retinal pigment epithelium (RPE)-J cells. Methods The effect of US and/or MBs on the delivery of NPs containing Cy3-labeled siRNA was evaluated by fluorescence microscopy and flow cytometry. Potential toxicity of NPs and cell viability under different conditions of US and/or MBs were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Results The results obtained showed that low intensity US or 15–20% MBs could increase the delivery efficiency of a lower concentration of mPEG-PLGA-PLL NPs loading siRNA to RPE-J cells, whereas the combination of US with MBs under the optimal conditions for the enhancement of NPs delivery did not further increase the cellular uptake of NPs compared to either US or MBs alone (p = 0.072 and p = 0.488, respectively). Under the optimal condition for US-enhanced NPs delivery, the enhanced PDGF-BB gene silencing with a combination of US and NPs encapsulating siRNA resulted in a significant decrease of mRNA and protein expression levels compared to NPs alone. Conclusions US and/or MBs could be used safely to enhance the delivery of NPs loading siRNA to rat RPE-J cells. A combination of the chemical (mPEG-PLGA-PLL NPs loading siRNA) and physical (US) approaches could more effectively downregulate the mRNA and protein expression of PDGF-BB. Copyright © 2011 John Wiley & Sons, Ltd.

Using esterification-polymerization two-steps synthesis method, two kinds of comb-like polycarboxylate agents of BT and JS were synthesized by controlling acid-ester ratio. The adsorption characteristics of Ca2+ions on comb-like polycarboxylate polymers in the CaCl2solution were studied. The results indicated that the adsorption behavior was closely related to the structure of polymers, the adsorption power of JS with water-reducing structure was strong, while weak with slump loss resisting polymers BT. The adsorption behavior was also in connection with the acid-ester ratio of polymer structure, the higher the acid-ester ratio is, the greater the absorption power; On the contrary, it will be smaller.

For the first time, a new kind of polycarboxylic acid high-performance water reducer, with ultra-high water reducing performance, was prepared through one-step polymerization, using new type polyether TPEG and acrylic acid as raw materials. Maximum water-reducing ratio of TPC may reach 50%. The most distinguishing characteristic of TPC was its reaction character at normal temperatures (30°C), which was of great practical significance for energy conservation and pollution reduction.

Peroxisome proliferator-activated receptor-alpha (PPAR-α) activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-αactivation reduces the expression of inflammatory cytokines, such as interleukin-6 (IL-6). Fenofibrate also induces cytochrome P450 4A (CYP4A) and increases 20-hydroxyeicosatetraenoic acid (20-HETE) production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2), while increasing expression of renal CYP4A during 7 days of DOCA-salt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5 mg/g) treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically). Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23) and soluble expoxide hydrolase (sEH) expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-αactivation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-αactivation protects the kidney against renal injury via decreased COX-2 expression.

A 3,5-dimethylphenylcarbamate derivative of cellulose immobilized onto the aminopropyl-modified silica gel was used as a chiral stationary phase and separation of five enantiomers was successfully performed by a home-made chiral capillary liquid chromatography system. Different chromatographic parameters such as resolution, column efficiency, and retention time were comparatively investigated using three chiral stationary phases with different coatings. The key factors which may influence the performance of the chiral stationary phases were evaluated by varying the composition of the mobile phase and its flow rate. It was illustrated that the self-installed chiral separation system was characterized by simplicity, high resolution, ease for practical usage, and could be handily applied for enantioseparation at the conventional laboratory.

For the first time, a brand new microemulsion system (water/span80/Triton X-100/n-hexyl alcohol/n-octane) was studied and applied to prepare nanosized zirconia. In total, three types of aqueous phases (distilled water, 2.0 M ammonia solution, and 0.8 M ZrOCl2 aqueous solution) have been studied, leading to three different ternary phase diagrams. This work indicates that such microemulsion system has two distinct advantages: on the one hand, significant improvement in the solubilization capability has been obtained (as high as 50 vol.% water content can be achieved in our case in compared with the maximum value around 30 vol.% as in previous reported ones); on the other hand, the cloudy point in our system can be manipulated in a wide range by simply adjusting the content of Triton X-100. Taking these advantages into account, we have successfully prepared nanosized zirconia utilizing this system. Furthermore, the analyses of the recorded DTA, XRD, and TEM spectroscopies have revealed that the calcination conditions are essential for the crystal growth of nanosized zirconia.

Plasmid(p) DNA was condensed by polycationic peptide polylysine (PLL) to be a core and then encapsulated in biodegradable monomethoxy (polyethyleneglycol)-poly(lactide-co-glycolide)-monomethoxy (poly-ethylene glycol) (PELGE) to form core-shell nanoparticles as a novel gene delivery system PPD (PELGE-PLL-DNA). Nanoparticles formed from PPD had several complementary properties such as improved biocompatibility, decreased cytotoxicity, enhanced pDNA integrity, and the characteristic of lysosomal escape as PLGA nanoparticles. The results demonstrated the potential of this PPD as an efficient gene delivery system.

TNF induces bone loss in common bone diseases by promoting osteoclast formation directly and indirectly, but it also limits osteoclast formation by inducing expression of NF-κB p100. Osteoclast precursors (OCPs) are derived from M1 (inflammatory) and M2 (resident) macrophages. However, it is not known if TNF stimulates or limits osteoclast formation through regulation of M1 or M2 differentiation or if RelB, a partner of p100, is involved. To investigate these questions, we treated bone marrow cells (BMCs) with M-CSF alone or in combination with TNF to enrich for OCPs, which we called M-OCPs and T-OCPs, respectively. We found that TNF switched CD11b+F4/80+ M-OCPs from Ly6C-Gr1- M2 to Ly6C+Gr1-CD11c+ and Ly6C-Gr1-CD11c+ M1 cells. RANKL induced osteoclast formation from both Ly6C+Gr1- and Ly6C-Gr1- T-OCPs, but only from Ly6C+Gr1- M-OCPs, which formed significantly fewer osteoclasts than T-OCPs. Importantly, Ly6C+Gr1- cells from both M- and T-OCPs have increased expression of the M1 marker genes, iNOS, TNF, IL-1β and TGFβ1, compared to Ly6C-Gr1- cells, and Ly6C-Gr1- cells from T-OCPs also have increased expression of iNOS and TGFβ1 compared to cells from M-OCPs. Both RANKL and TNF increased RelB mRNA expression. TNF significantly increased RelB protein levels, but RANKL did not because it also induced RelB proteasomal degradation. TNF inhibited RANKL-induced NFATc1 mRNA expression and osteoclast formation from M-OCPs, but not from T-OCPs, and it did not induce Ly6C+Gr1-CD11c+ or Ly6C-Gr1-CD11c+ M1 macrophages from RelB-/- BMCs. Furthermore, overexpression of RelB in M-OCPs reduced RANKL-induced osteoclast formation and NFATc1 mRNA expression, but it increased TNF-induced OC formation without affecting NFATc1 levels. Thus, TNF induction of RelB directly mediates terminal osteoclast differentiation independent of NFATc1 and limits RANKL-induced osteoclastogenesis by inhibiting NFATc1 activation. However, the dominant role of TNF is to expand the OCP pool by switching the differentiation of M-CSF-induced M2 to M1 macrophages with enhanced osteoclast forming potential. Strategies to degrade RelB could prevent TNF-induced M2/M1 switching and reduce osteoclast formation.

The objective of this study was to evaluate the in vivo characteristics of poly (ethylene glycol)-poly (lacticacid-co-glycolicacid)-poly (ethylene- glycol) (PELGE) copolymers as drug carriers. In order to test this circulation time, mitoxantrone (DHAQ) was used as a model drug in this study. DHAQ nanoparticles (DHAQ-NP) were prepared, subsequently the DHAQ-NP were evaluated by measuring the drug concentration in plasma after intravenous administration via the tail vein of mice. The circulation time of the DHAQ-NP were tested. The results showed prolonged mitoxantrone (DHAQ) residence in systemic blood circulation.

During the biosynthesis of natural products, the intra-molecular distribution of isotopes is introduced as a result of different isotope effects associated with the reactions involved. Due to the sensitivity of certain enzymes to the presence of a heavy isotope, the isotope selection effects related to some transformations can be high, especially for hydrogen. The effect of a series of isotope effects specific to each enzyme-catalysed step are additive during a biosynthetic pathway, leading to fractionation of the isotopes between the starting substrate and the final product. As the individual reactions are acting on different positions in the substrate, the net effect is a non-statistical distribution of isotope within the final product. Quantitative 2H NMR spectroscopy can be used to measure the distribution of 2H at natural abundance in natural products. In the first example, the fermentation of glucose is examined. Glucose can act as a primary carbon source for a wide range of fermentation products, produced by a variety of pathways. In many cases, competing pathways are active simultaneously. The relative fluxes are influenced by both environmental and genetic parameters. Quantitative 2H NMR spectroscopy is being used to obtain mechanistic and regulatory information about isotopic fractionation from glucose during such fermentations. Quantitative 2H NMR spectroscopy can also be used to examine the fractionation in 2H that occurs in long-chain fatty acids during chain elongation and oxygenation. It has been found that the (2H/1H) ratio shows an alternating pattern along the length of the chain and that the residual hydrogen atoms at the sites of desaturation are asymmetrically impoverished. The extent to which the non-statistical distribution of isotopes can be related to the mechanism of enzymes involved in the biosynthetic pathway via kinetic isotopic effects will be discussed.

OBJECTIVE: To establish equations for the estimation of glomerular filtration rates (eGFRs) based on serum creatinine (SCr) and/or serum cystatin C (SCysC) in Chinese patients with chronic kidney disease (CKD), and to compare the new equations with both the reference GFR (rGFR) and the literature equations to evaluate their applicability. METHODS: The 788 Chinese CKD patients were randomly divided into two groups, the training group and the testing group, to establish new eGFR-formulas based on serum CysC and to validate the established formulas, respectively. (99m)Tc-DTPA clearance (as the rGFR), serum Cr, and serum CysC were determined for all patients, and GFR was calculated using the Cockcroft-Gault equation (eGFR1), the MDRD formula (eGFR2), the CKD-EPI formulas (eGFR3, eGFR4), and the Chinese eGFR Investigation Collaboration formulas (eGFR5, eGFR6). The accuracy of each eGFR was compared with the rGFR. RESULTS: The training and testing groups' mean GFRs were 50.84±31.36 mL/min/1.73 m(2) and 54.16±29.45 mL/min/1.73 m(2), respectively. The two newly developed eGFR formulas were fitted using iterative computation: [Formula: see text] and [Formula: see text]. Significant correlation was observed between each eGFR and the rGFR. However, proportional errors and constant errors were observed between rGFR and eGFR1, eGFR2, eGFR4, eGFR5 or eGFR6, and constant errors were observed between eGFR3 and rGFR, as revealed by the Passing & Bablok plot analysis. The Bland-Altman analysis illustrated that the 95% limits of agreement of all equations exceeded the previously accepted limits of

Previous reports suggest peroxisome proliferator-activated receptor-α (PPAR-α) agonist attenuates hypertension by suppressing oxidative stress and increasing superoxide dismutase (SOD) activity. We tested the hypothesis that the absence of PPAR-α would increase NADPH oxidase (NOX)2, NOX4 and decrease SOD expression in mice heart and kidneys during Ang II hypertension. Male (10 - 12 weeks old) PPAR-α knockout (KO) mice and their wild-type (WT) controls were implanted with biotelemetry devices and infused with a slow pressor dose of Ang II (400 ng/kg/min) for 12 days. Separate groups of KO + Ang II and WT + Ang II mice were given the NOX inhibitor, apocynin (1 g/L) or PPAR-α agonist, fenofibrate (145 mg/kg/day). Mean arterial pressure (MAP) was similar between KO (119 ± 2 mmHg) and WT (122 ± 2 mmHg) during the control period. On day 12 of Ang II, MAP was significantly higher in KO than WT, 161 ± 5 and 145 ± 4 mmHg, respectively. Fenofibrate significantly reduced MAP in WT + Ang II mice (134 ± 5 mmHg) and apocynin reduced MAP in KO + Ang II and WT + Ang II mice. Heart and kidney NOX2 expression were significantly increased (61 ± 5% and 33 ± 5 %, respectively) in KO + Ang II when compared to WT + Ang II mice. Apocynin treatment significantly reduced heart and kidney NOX2 expression in KO + Ang II mice. Heart NOX4 expression was significantly decreased (28 ± 3%) in WT + Ang II mice when compared to WT controls. No significant changes were observed in KO + Ang II heart NOX4 expression. Kidney NOX4 expression was significantly decreased in both Ang II-treated KO (77 ± 5%) and WT (50 ± 5%) mice when compared to their respective controls. WT + Ang II SOD expression in the heart was significantly lower than WT controls. Ang II did not lower heart SOD expression in KO mice. SOD expression in the kidneys was significantly decreased in KO + Ang II and WT + Ang II when compared to their respective controls. Fenofibrate significantly increased kidney SOD expression in WT + Ang II mice above WT controls. Fenofibrate did not significantly increase kidney SOD expression in KO + Ang II mice above KO controls. Our results suggest that increased heart and kidney NOX2 expression, along with decreased SOD expression in PPAR-α KO mice contributes to significant increases in MAP during Ang II hypertension.

The anti-inflammatory properties of PPAR-αplays an important role in attenuating hypertension. The current study determines the anti-hypertensive and anti-inflammatory role of PPAR-αagonist during a slow-pressor dose of Ang II (400 ng/kg/min). Ten to twelve week old male PPAR-αKO mice and their WT controls were implanted with telemetry devices and infused with Ang II for 12 days. On day 12 of Ang II infusion, MAP was elevated in PPAR-αKO mice compared to WT (161±4 mmHg versus145±4 mmHg) and fenofibrate (145 mg/kg/day) reduced MAP in WT + Ang II mice (134±7 mmHg). Plasma IL-6 levels were higher in PPAR-αKO mice on day 12 of Ang II infusion (30±4versus8±2 pg/mL) and fenofibrate reduced plasma IL-6 in Ang II-treated WT mice (10±3 pg/mL). Fenofibrate increased renal expression of CYP4A, restored renal CYP2J expression, reduced the elevation in renal ICAM-1, MCP-1 and COX-2 in WT + Ang II mice. Our results demonstrate that activation of PPAR-αattenuates Ang II-induced hypertension through up-regulation of CYP4A and CYP2J and an attenuation of inflammatory markers such as plasma IL-6, renal MCP-1, renal expression of ICAM-1 and COX-2.

The prion protein peptide PrP106-126 induces cell apoptosis through mechanisms involving production of intracellular reactive oxygen species. The present study investigated the effects of edaravone, a potent free radical scavenger in clinical use, on cell cytotoxicity induced by PrP106-126. Results showed that PrP106-126 decreased PC12 cell viability in a dose- and time-dependent manner. Edaravone significantly antagonized the cytotoxic effects of PrP106-126. Mechanistically, PrP106-126 decreased PC 12 intracellular glutathione (GSH) concentrations, decreased superoxide dismutase (SOD) enzyme activity, increased concentrations of the oxidation end product malondialdehyde (MDA), depolarized the mitochondrial membrane, and increased caspase-3 activity. Edaravone alone did not affect GSH, SOD, or MDA but did effectively reverse all of the intracellular prooxidant effects induced by PrP106-126 and inhibit induced apoptosis in PC12 cells. In conclusion, edaravone may be a viable candidate for the treatment of oxidative stress-induced neurodegenerative disease. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:235–241, 2010; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20330

PURPOSE: To determine the prevalence and association of epiretinal membranes (ERMs), as assessed by retinal photography and optical coherence tomography (OCT), in a Chinese population. METHODS: The Handan Eye Study is a population-based study of eye disease in rural Chinese aged 30+ years. Eligible residents underwent a detailed ophthalmic examination including retinal photography and Stratus OCT. ERMs were defined by a combination of retinal photographs and OCT and classified as cellophane macular reflex (CMR) or preretinal macular fibrosis (PMF) based on retinal photographs characteristics. RESULTS: Of the 6830 persons examined, 6565 (96.1%) had gradable retinal photographs and/or OCT. The mean age was 51.7 +/- 11.6 years. ERMs were present in 3.4% (95% CI: 2.9%-3.8%) of participants, bilateral in 20.3% of the cases. CMR was present in 2.2% and PMF in 0.7%, and ERMs were unclassified in 0.5% (detected by OCT only). ERM prevalence was similar in women and men (3.6% vs. 3.1%), strongly associated with increasing age (P for trend < 0.001). After adjustment for age and sex, primary ERM was associated positively with myopia (OR: 1.58, 95% CI: 1.12-2.23) and inversely with current smoking (OR: 0.61, 95% CI: 0.38-0.97, versus never smoked). Best corrected visual acuity was significantly worse in eyes with primary ERMs (mean LogMAR score lower by 0.07, 95% CI: 0.05-0.10) than eyes without ERMs, after adjustment for age, sex, and lens status. CONCLUSIONS: ERMs affect 3.4% of the population 30+ years of age and living in rural China. Idiopathic ERMs were associated with myopia, decreased visual acuity, and inversely associated with smoking.

Quantitative (2)H NMR spectroscopy can determine the natural abundance ((2)H/(1)H) ratio at each site of a molecule. In natural products, variation in these values is related to the reaction mechanisms in the pertinent biosynthetic pathway. For the first time, this novel approach has been exploited to probe for mechanistic differences in the introduction of different functionalities into a long-chain fatty acid. Vernolic acid, a major component of the seed oil of Vernonia galamensis, contains both an epoxide and a desaturation. The site-specific isotopic distribution ((2)H/(1)H)(i) has been determined for both vernolic acid and linoleic acid isolated from the same V. galamensis oil. It is found that the ((2)H/(1)H) ratio of vernolic acid shows a pattern along the entire length of the chain, consistent with linoleic acid being its immediate precursor. Notably, the C13 relates to the C13 of linoleic acid but not to the C13 of oleic acid. Furthermore, the C12 and C13 positions in vernolic acid are less depleted, consistent with a change in hybridization state from sp(2) to sp(3). However, the C11 position shows a marked relative enrichment in the vernolic acid, implying that it plays a role in the epoxidase but not the desaturase mechanism. Thus, although it can be concluded that the catalytic mechanisms for the epoxidase and desaturase activities are similar, marked differences in the residual ((2)H/(1)H) patterns indicate that the reaction mechanisms are not identical.

In the title compound, C4H4N2O2, both imidazole N atoms are protonated and carboxylate group is deprotonated, resulting in a zwitterion. The molecule is essentially planar, with an r.m.s. deviation of 0.012 (1) Å. In the crystal, N—H...O hydrogen bonds and π–π stacking interactions [centroid–centroid distance = 3.674 (2) Å] between the imidazole rings link the molecules into a three-dimensional supramolecular network.

Quantitative (2)H NMR spectroscopy has been used to measure the distribution of deuterium at natural abundance in long-chain fatty acids extracted from the same vegetable oil. Peanut seed oil was selected, due to its suitable oleic and linoleic acid content. The methyl esters of the fatty acids were prepared by transesterification and isolated by modified argentation column chromatography on silica. In order to measure the natural isotopic fractionation of deuterium (D) at the maximum number of positions, the purified methyl oleate and methyl linoleate were chemically cleaved and the (D/H)(i) values determined by quantitative (2)H NMR spectroscopy. It was thus possible to demonstrate that fractionation in deuterium occurs during the desaturation of oleate to linoleate. Furthermore, the previously observed distribution of deuterium at the sites of desaturation is confirmed, as is the alternating pattern of (D/H)(i), which relates to the origin of the pertinent hydrogen atoms. The data obtained are discussed in terms of the kinetic isotopic effects intrinsic to the enzymes-synthetases and desaturases-involved in the biosynthesis of fatty acids.