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Acutely increased renal venous pressure (RVP) impairs renal function, but the long-term impact is unknown. We investigated whether chronic RVP elevation impairs baseline renal function and prevents exacerbation of renal dysfunction and cardiovascular instability upon further RVP increase. RVP elevation (20 –25 mmHg) or sham operation (sham) was performed in rats. After 1 wk (n=17) or 3 wk (n = 22), blood pressure, RVP, renal blood flow (RBF), renal vascular conductance (RVC), and glomerular filtration rate (GFR) were measured at baseline and during superimposed RVP increase. Chronic RVP elevation induced extensive renal venous collateral formation. RVP fell to 6±1 mmHg at 1 wk and 3 ±1 mmHg at 3 wk. Baseline blood pressure and heart rate were unaltered compared with sham. RBF, RVC, and GFR were reduced at 1 wk but normalized by 3 wk. Upon further RVP increase, the drop in mean arterial pressure was attenuated at 3 wk compared with 1 wk (P < 0.05), whereas heart rate fell comparably across all groups; the mean arterial pressure-heart rate relationship was disrupted at 1 and 3 wk. RBF fell to a similar degree as sham at 1 wk (–2.3±0.7 vs. – 3.9 ± 1.2 mL/min, P = 0.066); however, at 3 wk, this was attenuated compared with sham (–1.5 ± 0.5 vs. 4.2± 0.7 mL/min, P < 0.05). The drop in RVC and GFR was attenuated at 1 and 3 wk (P < 0.05). Thus, chronic RVP elevation induced by partial renal vein ligation elicits extensive renal venous collateral formation, and although baseline renal function is impaired, chronic RVP elevation in this manner induces protective adaptations in kidneys of healthy rats, which attenuates the hemodynamic response to further RVP increase. [ABSTRACT FROM AUTHOR]

Increased central venous pressure and renal venous pressure (RVP) are associated with worsening of renal function in acute exacerbation of congestive heart failure. We tested whether an acute isolated elevation of RVP in one kidney leads to ipsilateral renal vasoconstriction and decreased glomerular filtration rate (GFR) and whether this depends on dietary salt intake or activation of renal nerves. Male Lewis rats received a normal (1% NaCl, NS) or high-salt (6% NaCl) diet for ≥14 days before the acute experiment. Rats were then randomized into the following three groups: time control and RVP elevation to either 10 or 20 mmHg to assess heart rate, renal blood flow (RBF), and GFR. To increase RVP, the left renal vein was partially occluded for 120 min. To determine the role of renal nerves, surgical denervation was conducted in rats on both diets. Renal sympathetic nerve activity (RSNA) was additionally recorded in a separate group of rats. Increasing RVP to 20 mmHg decreased ipsilateral RBF (7.5 ± 0.4 to 4.1 ± 0.7 ml/min, P<0.001), renal vascular conductance (0.082 ± 0.006 to 0.060 ± 0.011 ml· min-1 ·mmHg-1 , P<0.05), and GFR (1.28 ± 0.08 to 0.40 ± 0.13 ml/min, P<0.05) in NS rats. The reduction was abolished by high-salt diet but not by renal denervation. Furthermore, a major increase of RVP (1.6 ± 0.8 to 24.7 ± 1.2 mmHg) immediately suppressed RSNA and decreased heart rate (P<0.05), which points to suppression of both local and systemic sympathetic activity. Taken together, acute elevated RVP induces renal vasoconstriction and decreased GFR, which is more likely to be mediated via the renin-angiotensin system than via renal nerves. [ABSTRACT FROM AUTHOR]

A novel aromatic diamine monomer, 4-(4-(1-pyrrolidinyl)phenyl)-2,6-bis(4-(4- aminophenoxy)phenyl)pyridine (PPAPP) containing pyridine rings, pyrrolidine groups, and ether linkages, was successfully synthesized using 4-hydroxyacetophenone and 1-chloro-4-nitrobenzene as starting materials by three-step reactions, and then used to synthesize a series of polyimides by polycondensation with various aromatic dianhydrides via a two-step method. The structure of PPAPP was characterized by NMR, FT-IR, and mass spectrometry analysis methods. These polymers showed good solubility in common organic solvents (e.g., NMP, DMF, DMSO, and DMAc) at room temperature or on heating. Moreover, they presented a high thermal stability with the glass transition temperature (Tgs) exceeding 316 °C, as well as the temperature of 10% weight loss ranged from 552 to 580 °C with more than 67% residue at 800 °C under nitrogen. Furthermore, they also exhibited excellent hydrophobicity with a contact angle in the range of 85.6°-97.7°, and the results ofWide-Angle X-ray Diffraction (WAXD) indicated that all of the polymers revealed an amorphous structure. [ABSTRACT FROM AUTHOR]

Disorders of hepatic energy metabolism, which can be regulated by endoplasmic reticulum (ER) stress, lead to metabolic diseases such as hepatic steatosis and hypoglycemia. Tunicamycin, a pharmacological ER stress inducer, is used to develop an anti-cancer drug. However, the effects of tunicamycin on hepatic energy metabolism have not been well elucidated. Mice were intraperitoneally injected with tunicamycin or vehicle. Twenty-four hours later, hepatic triglyceride and glycogen content and serum lipids profiles were analyzed, as well as the expression of lipogenic and gluconeogenic genes. Tunicamycin significantly induced hepatic a yellowish color and ER stress, as well as increasing serum levels of aspartate transaminase and alanine transaminase. Besides, tunicamycin remarkably increased hepatic triglyceride content and suppressed the expression of apolipoprotein B100. In addition, tunicamycin-treated mice had lower serum levels of triglyceride, apolipoprotein B, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Gene expression of peroxisome proliferator-activated receptor α was decreased by tunicamycin, but the protein level was increased. Furthermore, blood glucose level and hepatic glycogen content were decreased in tunicamycin-treated mice. Protein kinase B signaling was attenuated in the tunicamycin-treated liver, but the expression and activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were unchanged. Tunicamycin alters hepatic energy homeostasis by increasing triglyceride accumulation and decreasing glycogen content. [ABSTRACT FROM AUTHOR]

Furosemide is a widely used, potent natriuretic drug, which inhibits the Na+-K+-2Cl- cotransporter (NKCC)-2 in the ascending limb of the loop of Henle applied to reduce extracellular fluid volume expansion in heart and kidney disease. Undesirable consequences of furosemide, such as worsening of kidney function and unpredictable effects on sodium balance, led to this critical evaluation of how inhibition of NKCC affects renal and cardiovascular physiology. This evaluation reveals important knowledge gaps, involving furosemide as a drug, the function of NKCC2 (and NKCC1), and renal and systemic indirect effects of NKCC inhibition. Regarding renal effects, renal blood flow and glomerular filtration rate could become compromised by activation of tubuloglomerular feedback or by renin release, particularly if renal function is already compromised. Modulation of the intrarenal renin angiotensin system, however, is ill-defined. Regarding systemic effects, vasodilation followed by nonspecific NKCC inhibition and changes in venous compliance are not well understood. Repetitive administration of furosemide induces short-term (braking phenomenon, acute diuretic resistance) and long-term (chronic diuretic resistance) adaptations, of which the mechanisms are not well known. Modulation of NKCC2 expression and activity in kidney and heart failure is ill-defined. Lastly, furosemide's effects on cutaneous sodium stores and on uric acid levels could be beneficial or detrimental. Concluding, a considerable knowledge gap is identified regarding a potent drug with a relatively specific renal target, NKCC2, and renal and systemic actions. Resolving these questions would increase the understanding of NKCCs and their actions and improve rational use of furosemide in pathophysiology of fluid volume expansion. [ABSTRACT FROM AUTHOR]

In this paper, the interaction between rare earth element Dy3+ and poly(Nvinylisobutyramide)(PNVIBA) polymer was investigated by using ultraviolet-visible (UV-vis), FT-Infrared (FT-IR), fluorescent spectroscopy and X-ray photoelectron spectroscopy (XPS) techniques. It was found that Dy3+ could coordinate with O in the C=O groups of PNVIBA pendant and form the Dy3+-PNVIBA complex. After forming the Dy3+-PNVIBA complex, the fluorescence emission intensity at 310 nm was significantly increased to 6.73 times comparing with that of the virgin PNVIBA polymer, because of the efficient intramolecular energy transfer from Dy3+ to PNVIBA. The Dy3+-PNVIBA complex could transform the short ultraviolet radiation to longer wavelength UV-B band radiation, and the complex displayed excellent bacterial inhibition activity than that of virgin PNVIBA. However, the low critical solution temperature (LCST) of PNVIBA was not obviously changed after the addition of a little amount of Dy3+. This novel thermosensitive complex of Dy3+-PNVIBA could be used as a potential functional material in many fields. [ABSTRACT FROM AUTHOR]

The ganglioside GM3 exerts its different effects via various growth factor receptors. The present study investigated and comparatively analyzed the opposing effects exerted by GM3 on the migration of mouse hepatocellular carcinoma Hepa1-6 cells via epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR/cMet). The results demonstrated that GM3 inhibited EGF-stimulated motility, but promoted HGF-stimulated motility of the Hepa1-6 cells via phosphatidylinositol 3-kinase/Akt-mediated migration signaling. It is well established that the main cytokines modulating cell proliferation, invasion and metastasis are different in different types of tumor. This difference may, at least in part, explain why GM3 exerted its actions in a tumor-type specific manner. [ABSTRACT FROM AUTHOR]

Multi-wavelength self-Raman laser from a passively Q-switched c-cut Nd: YVO4 laser at 1066.8 nm to four discrete Stokes lines at 1097.2, 1129.2, 1168.3 and 1178.8 nm is demonstrated simultaneously for the first time. With a 0.27 at% c-cut Nd:YVO4 crystal, the total output power of Stokes lines is 267 mW at a pump power of 5.0 W. [ABSTRACT FROM AUTHOR]

This study describes a new method to prepare monodisperse polystyrene (PS) colloidal nanoparticles with controlled size ranging from 60 nm to 140 nm by the direct polymerization of styrene and divinylbenzene inside the bilayers of the polydisperse hyperbranched polymer vesicles. [ABSTRACT FROM AUTHOR]

Background--Vitamin D deficiency is highly prevalent and is associated with dyshpidemia and cardiovascular disease. The impact of correcting vitamin D deficiency on blood lipids, strong cardiovascular disease prognostic factors, is unknown. Methods and Results--To determine relationships between 25-hydroxyvitamin D levels and lipids, we analyzed 4.06 million deidentified patient laboratory test results from September 2009 through February 2011. We performed a cross-sectional study of this population to determine associations between 25-hydroxyvitamin D levels and lipids across clinically defined strata. We also conducted a retrospective cohort study of vitamin D deficient patients to investigate how changes in 25-hydroxyvitamin D levels relate to changes in lipid levels. After exclusions, 107 811 patients with serial testing were selected for cross-sectional analysis. Compared with vitamin D deficient patients (<20 ng/mL), those with optimal levels (≤30 ng/mL) had lower mean total cholesterol (--1.9 mg/dL; 95% confidence interval [95% CI], -1.2 to -2.7; P<0.0001), lower low-density lipoprotein cholesterol (-5.2 mg/dL; 95% CI, -4.5 to -5.8; f<0.0001), higher high-density lipoprotein cholesterol (4.8 mg/dL; 95% CI, 4.5-5.0; P<0.0001), and lower triglycerides (--7.5 mg/dL; 95% CI, --6.2 to --8.7; P<0.0001). For the retrospective cohort analysis, raising vitamin D levels from <20 to ≤ 30 ng/mL (n=6260), compared with remaining at <20 ng/mL (n=2332), was associated with a mean increase in total cholesterol (0.77 mg/dL; 95% CI, 0.18-1.36; P=0.01) and high-density lipoprotein cholesterol (0.42 mg/dL; 95% CI, 0.08-0.76; P=0.02) but nonsignificant changes in low-density lipoprotein cholesterol (0.32 mg/dL; 95% CI, --0.01 to 0.66; F=0.06) and triglycerides (0.04 mg/dL; 95% CI, -2.16 to 2.23 mg/dL; P=0.97). Conclusions--Although vitamin D deficiency is associated with an unfavorable lipid profile in cross-sectional analyses, correcting for a deficiency might not translate into clinically meaningful changes in lipid concentrations; however, data from intervention trials are required to confirm these findings [ABSTRACT FROM AUTHOR]

Superconducting magnetic energy storage (SMES) system is an equipment that can help improving the stability of a power system. Location of SMES in multi-nodes power network plays a significant role for the stability improvement level. In this paper, based on the quantitative voltage stability index, genetic algorithm (GA) is used for optimization of the SMES location. The voltage stability index is used as the fitness function in GA. The GA mathematic parameters and optimal flow chart are presented. The proposed algorithm is tested in an IEEE 14-bus system. Simulation results show that the SMES is settled on the best site through GA optimization during the period of the voltage stability fault. [ABSTRACT FROM AUTHOR]

The use of lasers, over the past few decades, has emerged to be highly promising for cancer therapy modalities, most commonly the photothermal therapy method, which employs light absorbing dyes for achieving the photothermal damage of tumors, and the photodynamic therapy, which employs chemical photosensitizers that generate singlet oxygen that is capable of tumor destruction. However, recent advances in the field of nanoscience have seen the emergence of noble metal nanostructures with unique photophysical properties, well suited for applications in cancer phototherapy. Noble metal nanoparticles, on account of the phenomenon of surface plasmon resonance, possess strongly enhanced visible and near-infrared light absorption, several orders of magnitude more intense compared to conventional laser phototherapy agents. The use of plasmonic nanoparticles as highly enhanced photoabsorbing agents has thus introduced a much more selective and efficient cancer therapy strategy, viz. plasmonic photothermal therapy (PPTT). The synthetic tunability of the optothermal properties and the bio-targeting abilities of the plasmonic gold nanostructures make the PPTT method furthermore promising. In this review, we discuss the development of the PPTT method with special emphasis on the recent in vitro and in vivo success using gold nanospheres coupled with visible lasers and gold nanorods and silica–gold nanoshells coupled with near-infrared lasers. [ABSTRACT FROM AUTHOR]

Complexes [PF6⊂(Ag3(titmb)2](PF6)2 (8) and {SbF6⊂[Ag3(titmb)2](SbF6)2}·H2O·1.5 CH3OH (9) are obtained by reaction of titmb and Ag+ salts with different anions (PF6− and SbF6−), and crystal structures reveal that they are both M3L2 cage complexes with short Ag⋯F interactions between the silver atoms and the fluorine atoms of the anions. In complex 8, a novel cage dimer is formed by weak Ag⋯F contacts; an unique cage tetramer formed via Ag⋯π interactions (Ag⋯η5-imidazole) between dimers and an infinite 1D cage chain is presented. However, each of the external non-disordered SbF6− anions connect with six cage 9s via Ag⋯F contacts, and each cage 9 in turn connects with three SbF6− anions to form a 2D network cage layer; and the layers are connected by π–π interactions to form a 3D network. The anion-exchange reactions of four Ag3L2 type complexes ([BF4⊂(Ag3(titmb)2](BF4)2 (6), [ClO4⊂(Ag3(titmb)2](ClO4)2 (7b), [PF6⊂(Ag3(titmb)2](PF6)2 (8) and [SbF6⊂(Ag3(titmb)2](SbF6)2·1.5CH3OH (9)) with tetrahedral and octahedral anions (ClO4−, BF4−, PF6− and SbF6−) are also reported. The anion-exchange experiments demonstrate that the anion selective order is SbF6− > PF6− > BF4−, ClO4−, and this anion receptor is preferred to trap octahedral and tetrahedral anions rather than linear or triangle anions; SbF6− is the biggest and most preferable one, so far. The dimensions of cage complexes with or without internal anions, anion-exchange reactions, cage assembly and anion inclusions, silver(i) coordination environments, Ag–F and Ag–π interactions of Ag3L2 complexes 1–9 are discussed. [ABSTRACT FROM AUTHOR]

Complexes [PF6⊂(Ag3(titmb)2](PF6)2 (8) and {SbF6⊂[Ag3(titmb)2](SbF6)2}·H2O·1.5 CH3OH (9) are obtained by reaction of titmb and Ag+ salts with different anions (PF6− and SbF6−), and crystal structures reveal that they are both M3L2 cage complexes with short Ag⋯F interactions between the silver atoms and the fluorine atoms of the anions. In complex 8, a novel cage dimer is formed by weak Ag⋯F contacts; an unique cage tetramer formed via Ag⋯π interactions (Ag⋯η5-imidazole) between dimers and an infinite 1D cage chain is presented. However, each of the external non-disordered SbF6− anions connect with six cage 9s via Ag⋯F contacts, and each cage 9 in turn connects with three SbF6− anions to form a 2D network cage layer; and the layers are connected by π–π interactions to form a 3D network. The anion-exchange reactions of four Ag3L2 type complexes ([BF4⊂(Ag3(titmb)2](BF4)2 (6), [ClO4⊂(Ag3(titmb)2](ClO4)2 (7b), [PF6⊂(Ag3(titmb)2](PF6)2 (8) and [SbF6⊂(Ag3(titmb)2](SbF6)2·1.5CH3OH (9)) with tetrahedral and octahedral anions (ClO4−, BF4−, PF6− and SbF6−) are also reported. The anion-exchange experiments demonstrate that the anion selective order is SbF6− > PF6− > BF4−, ClO4−, and this anion receptor is preferred to trap octahedral and tetrahedral anions rather than linear or triangle anions; SbF6− is the biggest and most preferable one, so far. The dimensions of cage complexes with or without internal anions, anion-exchange reactions, cage assembly and anion inclusions, silver(i) coordination environments, Ag–F and Ag–π interactions of Ag3L2 complexes 1–9 are discussed. [ABSTRACT FROM AUTHOR]

A method for rapidly assembling high-density DNA arrays with near-perfect order is described. Photolithography is used to generate a wafer-scale array of microwells in a layer of photoresist on a chemically functionalized glass coverslip. The array is enclosed within a microfluidic device, and a suspension of superparamagnetic microbeads conjugated to DNA molecules is introduced into the chamber. A permanent magnet is used to direct the rapid assembly of the beads into the wells, with each well containing a single bead. These beads are immobilized on the glass surface via affinity binding, and excess beads can be recycled or washed away. Nonspecifically bound beads are removed by dissolving the photoresist. The result is a high-density array of beads with virtually no background. This method can be used to produce protein arrays for chip-based assays and DNA arrays for genotyping or genome sequencing. [ABSTRACT FROM AUTHOR]

The cyclooxygenase-2 (COX-2) enzyme is induced upon inflammation and in neoplastic tissues. It produces prostaglandins that stimulate tumor angiogenesis and tumor growth. Therefore, destruction and/or specific inhibition of COX-2 should be an important aspect of future tumor therapy. Recently, clinical application of specific COX-2 inhibitors called coxibs became doubtfully because they produce serious renal and cardiovascular complications under long term application. The exact underlying mechanisms are poorly understood and the different effects of diverse coxibs are not explained. It has been demonstrated before that COX-2 is degraded by the ubiquitin (Ub) proteasome system (UPS). However, how ubiquitination is accomplished and regulated was unclear. An important regulator of the UPS is the COP9 signalosome (CSN), which controls the stability of many proteins. Here we show that the proteasome-dependent degradation of COX-2 in HeLa cell lysate and in HeLa cells was stimulated by curcumin, an inhibitor of CSN-associated kinases. These data suggest a function of the CSN in the degradation of COX-2. In addition, proteolysis of COX-2 was significantly accelerated by parecoxib, but not by celecoxib or rofecoxib. By density gradient centrifugation and immunoprecipitation we demonstrate that COX-2 physically interacts with the CSN. Moreover, COX-2 is associated with large complexes consisting of the CSN, cullin-RING Ub ligases and the 26S proteasome. Pulldown experiments with Flag-COX-2 revealed cullin 1 and cullin 4 as components of the large super-complexes. Cullin 1 and 4 are scaffolding proteins of Ub ligases that presumably ubiquitinate COX-2. Treatment of HeLa cells with parecoxib results in an accelerated degradation of endogenous COX-2 accompanied by an increase of COX-2-Ub conjugates. In HeLa cells parecoxib is converted to the selective COX-2 inhibitor valdecoxib. Addition of valdecoxib also stimulates COX-2 degradation in HeLa cells. We therefore conclude that valdecoxib specifically interacts with COX-2 and induces a conformation accessible for ubiquitination and degradation. [ABSTRACT FROM AUTHOR]

Human oral cancer cells are found to assemble and align gold nanorods conjugated to anti-epidermal growth factor receptor (anti-EGFR) antibodies. Immnoconjugated gold nanorods and nanospheres were shown previously to exhibit strong Rayleigh (Mie) scattering useful for imaging. In the present letter, molecules near the nanorods on the cancer cells are found to give a Raman spectrum that is greatly enhanced (due to the high surface plasmon field of the nanorod assembly in which their extended surface plasmon fields overlap), sharp (due to a homogeneous environment), and polarized (due to anisotropic alignments). These observed properties can be used as diagnostic signatures for cancer cells. [ABSTRACT FROM AUTHOR]

The COP9 signalosome (CSN) occurs in all eukaryotic cells. It is a regulatory particle of the ubiquitin (Ub)/26S proteasome system. The eight subunits of the CSN possess sequence homologies with the polypeptides of the 26S proteasome lid complex and just like the lid, the CSN consists of six subunits with PCI (proteasome, COP9 signalosome, initiation factor 3) domains and two components with MPN (Mpr-Pad1-N-terminal) domains. Here we show that the CSN directly interacts with the 26S proteasome and competes with the lid, which has consequences for the peptidase activity of the 26S proteasome in vitro. Flag-CSN2 was permanently expressed in mouse B8 fibroblasts and Flag pull-down experiments revealed the formation of an intact Flag-CSN complex, which is associated with the 26S proteasome. In addition, the Flag pull-downs also precipitated cullins indicating the existence of super-complexes consisting of the CSN, the 26S proteasome and cullin-based Ub ligases. Permanent expression of a chimerical subunit (Flag-CSN2-Rpn6) consisting of the N-terminal 343 amino acids of CSN2 and of the PCI domain of S9/Rpn6, the paralog of CSN2 in the lid complex, did not lead to the assembly of an intact complex showing that the PCI domain of CSN2 is important for complex formation. The consequence of permanent Flag-CSN2 overexpression was de-novo assembly of the CSN complex connected with an accelerated degradation of p53 and stabilization of c-Jun in B8 cells. The possible role of super-complexes composed of the CSN, the 26S proteasome and of Ub ligases in the regulation of protein stability is discussed. [ABSTRACT FROM AUTHOR]

Bulky biaryl phosphine ligands facilitate Pd-catalyzed C--O coupling reactions of aryl halides with primary and secondary alcohols by promoting reductive elimination at the expense of β-hydride elimination. The key to their success is the ability to match the size of the ligand to that of the combination of substrates. The efficient coupling of a number of unactivated aryl chlorides and bromides with cyclic and acyclic secondary alcohols was achieved. This included the coupling of allylic alcohols for the first time in a Pd-catalyzed coupling process. [ABSTRACT FROM AUTHOR]

Background: Inhibition of the COP9 signalosome (CSN) associated kinases CK2 and PKD by curcumin causes stabilization of the tumor suppressor p53. It has been shown that curcumin induces tumor cell death and apoptosis. Curcumin and emodin block the CSN-directed c-Jun signaling pathway, which results in diminished c-Jun steady state levels in HeLa cells. The aim of this work was to search for new CSN kinase inhibitors analogue to curcumin and emodin by means of an in silico screening method. Methods: Here we present a novel method to identify efficient inhibitors of CSN-associated kinases. Using curcumin and emodin as lead structures an in silico screening with our in-house database containing more than 106 structures was carried out. Thirty-five compounds were identified and further evaluated by the Lipinski's rule-of-five. Two groups of compounds can be clearly discriminated according to their structures: the curcumin-group and the emodin-group. The compounds were evaluated in in vitro kinase assays and in cell culture experiments. Results: The data revealed 3 compounds of the curcumin-group (e.g. piceatannol) and 4 of the emodin-group (e.g. anthrachinone) as potent inhibitors of CSN-associated kinases. Identified agents increased p53 levels and induced apoptosis in tumor cells as determined by annexin V-FITC binding, DNA fragmentation and caspase activity assays. Conclusion: Our data demonstrate that the new in silico screening method is highly efficient for identifying potential anti-tumor drugs. [ABSTRACT FROM AUTHOR]

Examines the use of copper catalyst for the amidation of aryl halides. Method for the N-arylation of imidazoles; Effect of diamine ligands on aryl amidation; Reactions of aryl iodides with amides.

Examines the DNA-binding specificities of zinc fingers and DNA microarrays. Use of a DNA microarray-based method to characterize sequence-specific DNA recognition; Advantages of microarray-binding experiments; Feasibility of using DNA microarrays for identification of putative transcription factor-binding sites.

Investigates the utility of electron-rich phosphine ligands as catalysts for the alpha-arylation of ketones. Effectivity of ligands to catalyze the reaction of ketones with aryl chlorides and aryl bromides; Effectivity of ligands BINAP and Xantphos compared to biphenyl-based ligands.

A series of fluorinated co-polyimide films based on the 6FDA-FTPPA/BAFL backbone were prepared from 4-(3-fluoro-4- (trifluoromethyl)phenyl)-2,6-bis(4-aminophenyl)pyridine (FTPPA), commercial 9,9-bis(4-aminophenyl)fluorene (BAFL), and 4,4'-(hexafluoroisopropylidene)diphthalic anhydride (6FDA), with varying ratios of FTPPA:BAFL units (3:1, 2:1, 1:1, 1: 2, and 1:3). Co-polyimides not only exhibit high thermal stability (Tg > 357°C), good optical properties (λcutoff > 327 nm) and hydrophobicity (contact angle >91.4°), but also favorable solubility properties in both high and low boiling organic solvents. The fractional free volume of the polymers was simulated using molecular mechanics and molecular dynamics and correlated with experimental gas separation data. The presence of bulky groups led to high FFVs (>17.8%) and the formation of large microcavities with diameters ranging from 5.48 to 5.72 A°, which efficiently increased gas permeability. In pure gas permeation experiments, the permeability coefficients of CO2 and He for the 6FDA-FTPPA/BAFL (3:1) film were 41.48 and 79.38 bar, respectively, which were superior to those of commercial Matrimid and Kapton in terms of gas permeability. In especial, the 6FDA-FTPPA/BAFL (1:2) and 6FDA-FTPPA/BAFL (1:3) in copolyimide membranes exhibited the most attractive separation performance for O2/N2 gas pairs, approaching the 1991 Roberson upper limit. [ABSTRACT FROM AUTHOR]

A siliceous mesocellular foam-immobilized Ru–TsDPEN complex exhibited excellent catalytic reactivity, enantioselectivity and reusability in the asymmetric transfer hydrogenation of an imine and ketones. [ABSTRACT FROM AUTHOR]

Discusses a study which intends to develop general reaction conditions for the palladium (Pd)-catalyzed amination of aryl tosylates and benzene sulfonates. Ligand effects in amination of an aryl tosylate; Pd-catalyzed C--N bond-forming processes; Copper-catalyzed reactions.

The deep surrounding rock is usually in the true triaxial stress state, and previous constitutive models based on the understanding of uniaxial and conventional triaxial test results have difficulty characterizing the degradation and fracture process of rock ductile--brittle failure under true triaxial stress state. Therefore, this study conducted a series of true triaxial tests to obtain the understanding of the ductile--brittle behaviour of rock, and then combined the test results and the Mogi--Coulomb strength criterion, and proposed calculation methods for the elastic modulus E, cohesion c and internal friction angle u and the evolution functions of E, c and ф of rock under true triaxial stresses. With the decreasing of the minimum principal stress σ3 or increasing of the intermediate principal stress σ2, the marble post-peak stress drop rate gradually increases, the ductility gradually weakens, and the brittleness significantly strengthens. The calculation method and evolution function of rock E, c and ф under true triaxial stress were proposed. E decreased at first and then tended to remain stable with the increasing of equivalent plastic strain increment dep. c and u slowly increased at first and then rapidly decreased. With a method of parameter degradation rate to realize post-peak stress drop rate to reflect the ductile--brittle characteristics, a new three-dimensional ductile--brittle deterioration mechanical model (3DBDM) was established. The proposed model can accurately characterize the influence of rσ and rσ on mechanical parameters, the ductile--brittle behaviour of rock under true triaxial stresses, and the asymmetric failure characteristics of surrounding rock after excavation of deep underground engineering. The proposed model can be reduced to elastic--perfectly plastic, elastic--brittle, cohesion weakening friction strengthening (CWFS), Mohr--Coulomb, and Drucker--Prager models. [ABSTRACT FROM AUTHOR]

Presents the study on the free-radical contraction of six-, seven- and eight-membered lactones by a 1,2-shift mechanism. Preparation of three regiochemically mono-O-labeled bromolactones; Photolysis in aqueous acetonitrile; Rate constants for ring contraction.

Objective The present study aimed to develop the utility of a nomogram based on clinical and radiomics as a tool for predicting post-acute pancreatitis diabetes mellitus (PPDM-A). Methods This retrospective investigation evaluated 244 patients with acute pancreatitis. Patients were randomized in a 7:3 ratio into training and validation cohorts. Radiomics feature selection was then achieved using the variance threshold, select best K, and least absolute shrinkage and selection operator methods. The area under the curve values, decision, and calibration curves have been used to determine the models' predictive value. Results The developed nomogram performed superior to the clinical model in the validation (0.815 vs 0.677, p = 0.016) and training cohorts (0.803 vs 0.683, p = 0.002). The calibration curves demonstrated that the expected and actual values were satisfactory. In contrast, decision curve analysis revealed a stronger relationship between the nomogram and net clinical value than with the distinct radiomics or clinical signature effects. Conclusion In summary, the findings of this study demonstrated that establishing a predictive nomogram as a non-invasive technique may be useful in predicting the risk of PPDM-A. Advances in knowledge This is the first time to use a CT radiomics nomogram to predict PPDM-A. The nomogram is conducive to the personalized prediction of patients. It only needs to input the patient’s information, and a simple addition operation can quantitatively obtain its risk. The resultant tool has the potential to provide new opportunities to treat or prevent PPDM-A more effectively. [ABSTRACT FROM AUTHOR]

Discloses the first palladium catalyst system for the Suzuki-Miyaura coupling of unactivated aryl tosylates. Aryl benzenesulfonates as substrates in the arylation of enolates derived from cyclic and acyclic ketones, β-dicarbonyl compounds and ester.

The article focuses on the study that analyzes the progression of hepatitis C virus (HCV) clearance in the U.S. and the need to monitor progress towards national elimination goals.

An admirable and efficient Nd∶YVO4 laser at 1085 nm is demonstrated with a compact 35 mm plano-plano cavity. A chosen narrow bandpass filter with high-transmittance (HT) coating at 1064 nm (T = 96%) and optimized part-reflection (PR) coating at 1085 nm (T = 15%) is used as the output coupler. In the continuous-wave (CW) regime, the maximum output power reaches 3110mW at the pump power of 11.41 W. Based on a Cr: YAG crystal with initial-transmittance of 91%, the first passively Q-switched Nd∶YVO4 laser at 1085 nm is achieved. When the pump power is changed from the threshold of 4.50 to 6.08 W, the dual-wavelength lines at 1064 and 1085 nm are generated simultaneously. However, at the pump power of above 6.08 W, the single-wavelength line at 1085 nm is achieved. The largest output power, the highest peak power, and the narrowest pulse width are 1615 mW, 878 W and 26.2 ns, respectively. [ABSTRACT FROM AUTHOR]

Background. Knowledge of the estimated proportion of hepatitis C virus (HCV)-infected persons with advanced fibrosis or cirrhosis is critical to estimating healthcare needs. Methods. We analyzed HCV-related testing conducted by Quest Diagnostics from January 2010 through December 2013. Tests included hepatitis C antibody, HCV RNA, HCV genotype (nucleic acid tests [NAT]), liver function tests, and platelet counts; patient age was also determined. Aspartate aminotransferase (AST)-to-platelet ratio (APRI) was calculated as = 100*(aspartate aminotransferase [AST]/upper limit of AST)/platelet. Fibrosis-4 (FIB-4) was calculated as (age × AST)/(platelet ×√ alanine aminotransferase [ALT]). Persons were "currently infected" if they had ≥1 positive HCV NAT; "in care" if a positive RNA test was followed <6 months by ≥1 additional NAT(s), or ALT, AST, and platelets <90 days, or any test ordered by an infectious diseases or gastroenterology specialist; and "evaluated for treatment" if they had a genotype test. Results. Approximately 10 million HCV test results were analyzed, representing 5.6 million unique patients. Of the 2.6 million patients with data to estimate liver disease, 5% were currently infected. Among those currently infected, APRI and FIB-4 scores indicated that 23% overall—and 27% among the cohort born during 1945–1965—had advanced fibrosis or cirrhosis at first diagnosis. A total of 54% of infected were in care and 51% of infected with advanced fibrosis or cirrhosis were evaluated for treatment. Conclusions. Testing from a large US commercial laboratory indicates that about 1 in 4 HCV-infected persons have levels of liver disease put them at highest risk for complications and could benefit from immediate antiviral therapy. [ABSTRACT FROM AUTHOR]

We conduct a comparative study on the efficiency and cell death pathways of continuous wave (cw) and nanosecond pulsed laser photothermal cancer therapy using gold nanospheres delivered to either the cytoplasm or nucleus of cancer cells. Cytoplasm localization is achieved using arginine-glycine-aspartate peptide modified gold nanospheres, which target integrin receptors on the cell surface and are subsequently internalized by the cells. Nuclear delivery is achieved by conjugating the gold nanospheres with nuclear localization sequence peptides originating from the simian virus. Photothermal experiments show that cell death can be induced with a single pulse of a nanosecond laser more efficiently than with a cw laser. When the cw laser is applied, gold nanospheres localized in the cytoplasm are more effective in inducing cell destruction than gold nanospheres localized at the nucleus. The opposite effect is observed when the nanosecond pulsed laser is used, suggesting that plasmonic field enhancement of the nonlinear absorption processes occurs at high localization of gold nanospheres at the nucleus. Cell death pathways are further investigated via a standard apoptosis kit to show that the cell death mechanisms depend on the type of laser used. While the cw laser induces cell death via apoptosis, the nanosecond pulsed laser leads to cell necrosis. These studies add mechanistic insight to gold nanoparticle-based photothermal therapy of cancer. [ABSTRACT FROM AUTHOR]

Novel methods and technologies that could extend and complement the capabilities of the prevailing fluorescence microscope in following the cell cycle under different perturbations are highly desirable in the area of biological and biomedical imaging. We report a newly designed instrument for long-term light scattering live cell imaging based on integrating a homebuilt environmental cell incubation minichamber and an angled dark-field illumination system into a conventional inverted light microscope. Peptide-conjugated gold nanoparticles that are selectively delivered to either the cytoplasmic or nuclear region of the cell are used as light scattering contrast agents. The new system enables us to carry out continuous and intermittence-free dark-field live cell imaging over several tens of hours. A variety of applications of this imaging system are demonstrated, such as monitoring the nuclear uptake of peptide-conjugated gold nanoparticles, tracking the full cycle of cancer cells from birth to division, following the chromosome dynamics during cell mitosis, and observing the intracellular distribution of gold nanoparticles after cell division. We also discuss the overall effect of nuclear targeting gold nanoparticles on the cell viability of parent and daughter cells. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about the article "Comparative Analysis of Conventional Papanicolaou Tests and a Fluid-Based Thin-Layer Method," by A. Limaye, A.J. Connor, X. Huang and R. Luff in a 2003 issue of the "Archives of Pathology & Laboratory Medicine."

The terpene trilactones (TTLs) are believed to be important for the pharmacological properties of Ginkgo biloba leaves extract. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is a critical enzyme involved in the biosynthetic pathway of TTLs. In this study, an 1.22kb fragment of 5' flanking region of the HMGR gene (GbHMGR), was isolated from G. biloba by genome walking. Extensive sequence analysis revealed the presence of evolutionarily conserved and over-represented putative cis-acting elements in light-regulated transcription, hormone signaling (gibberellic acid, jasmonate and salicylic acid), elicitor and stress responses (cold/dehydration responses), and plant defense signaling (W-box/WRKY) that are common to the promoter region of GbHMGR. EMSA analysis suggested possible functionality of W-box in GbHMGR promoter region. The behavior of gene transcripts in ginkgo callus upon light, low temperature, MeJA and SA treatments further verified the regulatory function of GbHMGR promoter. A significant positive relationship between gene expression level and total TTL contents suggested that GbHMGR might be one of key genes involved in TTL biosynthesis in G. biloba. [ABSTRACT FROM AUTHOR]

The COP9 signalosome (CSN) is a regulator of the ubiquitin (Ub) proteasome system (UPS). In the UPS, proteins are Ub-labeled for degradation by Ub ligases conferring substrate specificity. The CSN controls a large family of Ub ligases called cullin-RING ligases (CRLs), which ubiquitinate cell cycle regulators, transcription factors and DNA damage response proteins. The CSN possesses structural similarities with the 26S proteasome Lid complex and the translation initiation complex 3 (eIF3) indicating similar ancestry and function. Initial structures were obtained 14 years ago by 2D electron microscopy (EM). Recently, first 3D molecular models of the CSN were created on the basis of negative-stain EM and single-particle analysis, mostly with recombinant complexes. Here, we compare deneddylating activity and structural features of CSN complexes purified in an elaborate procedure from human erythrocytes and efficiently pulled down from mouse Flag-CSN2 B8 fibroblasts. In an in vitro deneddylation assay both the human and the mouse CSN complexes deneddylated Nedd8-Cul1 with comparable rates. 3D structural models of the erythrocyte CSN as well as of the mouse Flag-CSN were generated by negative stain EM and by cryo-EM. Both complexes show a central U-shaped segment from which several arms emanate. This structure, called the horseshoe, is formed by the PCI domain subunits. CSN5 and CSN6 point away from the horseshoe. Compared to 3D models of negatively stained CSN complexes, densities assigned to CSN2 and CSN4 are better defined in the cryo-map. Because biochemical and structural results obtained with CSN complexes isolated from human erythrocytes and purified by Flag-CSN pulldown from mouse B8 fibroblasts are very similar, Flag-CSN pulldowns are a proper alternative to CSN preparation from erythrocytes. [ABSTRACT FROM AUTHOR]

Background--Anticoagulation control with warfarin, as assessed by the international normalized ratio (INR), is challenging. Time in the therapeutic range has been inversely correlated with major hemorrhage, thrombosis, and mortality. Quest Diagnostics offers standardized INR laboratory testing services to approximately half of US physician practices. To inform national stroke prevention strategies, we evaluated anticoagulation control in office-based community practices. Methods and Results--We selected individuals with ≥2 months of INR data, INR results of >1.2, and an ICD-9 diagnosis code of atrial fibrillation. Frequency of INR testing and time in the therapeutic range were analyzed by age, sex, length of testing period, number of referred patients per provider, and median household income (based on home ZIP code). We identified 138319 individuals referred by 37939 physicians, yielding a total of 2683674 INR results. Patients had a mean age of 74 years; 81% were ≥65 years of age, and 55% were ≥75 years of age. The mean time in the therapeutic range was 53.7% overall and improved with time on treatment, increasing from 47.6% for patients with <6 months of testing to 57.5% for those with ≥6 months of testing (P<0.0001). The number of patients tested per physician practice was positively associated with time in the therapeutic range. Younger age, female sex, and lower income were also independently associated with poorer anticoagulant control. Conclusion--This study demonstrates widespread suboptimal anticoagulation control, suggesting an urgent need to improve oral anticoagulation care for most patient segments in the United States. [ABSTRACT FROM AUTHOR]

Noble metal nanoparticles (NPs) such as silver (Ag) and gold (Au) have unique plasmonic properties that give rise to surface enhanced Raman scattering (SERS). Generally, Ag NPs have much stronger plasmonic properties and, hence, provide stronger SERS signals than Au NPs. However, Ag NPs lack the chemical stability and biocompatibility of comparable Au NPs and typically exhibit the most intense plasmonic resonance at wavelengths much shorter than the optimal spectral region for many biomedical applications. To overcome these issues, various experimental efforts have been devoted to the synthesis of Ag/Au hybrid NPs for the purpose of SERS detections. However, a complete understanding on how the SERS enhancement depends on the chemical composition and structure of these nanoparticles has not been achieved. In this study, Mie theory and the discrete dipole approximation have been used to calculate the plasmonic spectra and near-field electromagnetic enhancements of Ag/Au hybrid NPs. In particular, we discuss how the electromagnetic enhancement depends on the mole fraction of Au in Ag/Au alloy NPs and how one may use extinction spectra to distinguish between Ag/Au alloyed NPs and Ag-Au core-shell NPs. We also show that for incident laser wavelengths between ∼410 nm and 520 nm, Ag/Au alloyed NPs provide better electromagnetic enhancement than pure Ag, pure Au, or Ag-Au core-shell structured NPs. Finally, we show that silica-core Ag/Au alloy shelled NPs provide even better performance than pure Ag/Au alloy or pure solid Ag and pure solid Au NPs. The theoretical results presented will be beneficial to the experimental efforts in optimizing the design of Ag/Au hybrid NPs for SERS-based detection methods. [ABSTRACT FROM AUTHOR]

Flowering Locus T (FT) can promote flowering in the plant photoperiod pathway and also facilitates vernalization flowering pathways and other ways to promote flowering. The expression of products of the FT gene is recognized as important parts of the flowering hormone and can induce flowering by long-distance transportation. In the present study, many FT-like genes were isolated, and the transgenic results show that FT gene can promote flowering in plants. This paper reviews the progress of the FT gene and its expression products to provide meaningful information for further studies of the functions of FT genes. [ABSTRACT FROM AUTHOR]

Multiple endocrine neoplasia type 1 (MEN1) results from mutations in tumor suppressor gene Men1, which encodes nuclear protein menin. Menin up-regulates certain cyclin-dependent kinase inhibitors through increasing histone H3 lysine 4 (H3K4) methylation and inhibits G0/G1 to S phase transition. However, little is known as to whether menin controls G2/M-phase transition, another important cell cycle checkpoint. Here, we show that menin expression delays G2/M phase transition and reduces expression of Ccnb2 (encoding cyclin B2). Menin associates with the promoter of Ccnb2 and reduces histone H3 acetylation, a positive chromatin marker for gene transcription, at the Ccnb2 locus. Moreover, Men1 ablation leads to an increase in cyclin B2 expression, histone H3 acetylation at the Ccnb2 locus, and G2/M transition. In contrast, knockdown of cyclin B2 diminishes the number of cells at M phase and reduces cell proliferation. Furthermore, menin interferes with binding of certain positive transcriptional regulators, such as nuclear factor Y (NF-Y), E2 factors (E2Fs), and histone acetyl-transferase CREB (cAMP-response element-binding protein)-binding protein (CBP) to the Ccnb2 locus. Notably, MEN1 disease-related mutations, A242V and L22R, abrogate the ability of menin to repress cyclin B2 expression and G2/M transition. Both of the mutants fail to reduce the acetylated level of the Ccnb2 locus. Together, these results suggest that menin-mediated repression of cyclin B2 is crucial for inhibiting G2/M transition and cell proliferation through a previously unrecognized molecular mechanism for menin-induced suppression of MEN1 tumorigenesis. [ABSTRACT FROM AUTHOR]

Abstract  Based on the synthesis of poly(N-isopropylacrylamide)-grafted poly(N-isopropylacrylamide-co-styrene) (PNNS) microsphere, Eu(III) was chosen to coordinate with PNNS. The interaction between Eu(III) and PNNS was characterized by using X-ray photoelectron spectroscopy, Fourier transform infrared, ultraviolet–visual and fluorescence spectroscopy. The results from experiments indicated that the Eu(III) is mainly bonded to O of the carbonyl groups of PNNS and formed the complex of PNNS–Eu(III). After forming the PNNS–Eu(III) complex, the emission fluorescence intensity of Eu(III) in the complex is significantly enhanced because the effective intramolecular energy-transfer from PNNS to Eu(III). Especially, the maximum emission intensity of the PNNS–Eu(III) complex at 614 nm is enhanced about 33 times comparing to that of the pure Eu(III). The intramolecular energy-transfer efficiency from PNNS to Eu(III) reaches 55%. [ABSTRACT FROM AUTHOR]

In the cross-coupling reactions of unprotected oxindoles with aryl halides, Pd- and Cu-based catalyst systems displayed orthogonal chemoselectivity. A Pd-dialkylbiarylphosphine-based catalyst system chemoselectively arylated oxindole at the 3 position, while arylation occurred exclusively at the nitrogen using a Cu-diamine-based catalyst system. Computational examination of the relevant L1Pd(Ar)(oxindolate) and diamine-Cu(oxindolate) species was performed to gain mechanistic insight into the controlling features of the observed chemoselectivity. [ABSTRACT FROM AUTHOR]

Abstract  We successfully prepared PNIPAM-g-P(NIPAM-co-St) (PNNS) core–shell microsphere by an emulsifier-free emulsion polymerization method. When PNNS with a core–shell structure is interacted with Eu(III), Eu(III) mainly bonds to oxygen of the carbonyl groups of PNNS, forming the novel PNNS-Eu(III) complex. It was found that the complex showed thermosensitive and fluorescent properties at one time. Especially, the maximum emission intensity of Eu(III) in the complex at 614 nm is significantly enhanced in comparison with that of pure Eu(III), demonstrating that there exists an efficient intermolecular energy transfer from the polymer ligand to Eu(III) and then the excited Eu(III) generates the enhanced fluorescence. When the weight ratio of Eu(III) and the PNNS is 8 wt%, the enhancement of the emission fluorescence intensity at 614 nm is highest. [ABSTRACT FROM AUTHOR]

Many industries use gas−liquid stirred-tank reactors with a third phase of buoyant particles. Few studies have looked at the effects of buoyant particle characteristics on solid−liquid suspension and gas−liquid dispersion, and even less have considered operation at elevated temperatures. This paper reports power consumption and gas holdup measurements made in a hot-sparged three-phase system. The vessel was a dished-base reactor of diameter 0.476 m (T) holding 0.145 m3of liquid, agitated by a multi-impeller agitator (a hollow half-elliptical blade dispersing turbine below two up-pumping wide-blade hydrofoils, identified as HEDT2WHU). This configuration has been recommended in previous work. Air, deionized water, and polypropylene (PP) particles were used in this work. The temperature of the water was in the range 80.5−82.5 °C. The results show that, as in a cold system, the effect of the solid concentration on aerated agitator power demand is negligible. There is little difference between the agitator power demand in cold- and hot-sparged systems, except that the relative (gassed-to-ungassed ratio) power demand, RPD, is a little higher in hot-sparged conditions. The influence of power consumption and gas rate on gas holdup is slightly less when hot than when cold. Gas holdup in the hot-sparged system, which, with similar total gas rates and power input, is only about one-half or two-thirds of that at room temperature, is slightly increased at higher solids concentrations. The reasons for the differences in gas dispersion between cold- and hot-sparged systems are analyzed and discussed in this paper, with further experimental and CFD studies planned for future work. [ABSTRACT FROM AUTHOR]

Therapeutic angiogenesis represents a novel approach to treat critical limb ischemia when revascularization is no more an option. The clinical use of the vascular endothelial growth factor is questioned, because of its side effects. This study was designed to identify and characterize human immunodeficiency virus type 1 (HIV-1) Tat-derived peptides based on their pro-angiogenic properties. A series of Tat-derived peptides were synthesized containing mutations in the basic domain. To minimize side effects Tat peptides were selected exerting no effects on the proteasome and on the viability of human umbilical vein endothelial cells (HUVEC). Tatpep5, 15, and 16 increased the endogenous levels of the pro-angiogenic transcription factors c-Jun and SP-1 as well as the production of the plasminogen activator inhibitor-1 (PAI-1) by HUVEC. A significant induction of endothelial cell invasion was observed upon treatment of HUVEC with Tat peptides. In addition, selected Tat peptides induced tube formation by HUVEC as visualized and quantified in a Matrigel matrix. Our data demonstrate that the selected Tat peptides fulfill essential criteria for pro-angiogenic substances. They represent the basis for the development of novel pro-angiogenic drugs for future therapeutic angiogenesis, which might be applied for treatment of unreconstructible critical limb ischemia. [ABSTRACT FROM AUTHOR]

In higher eukaryotic cells, the p53 protein is degraded by the ubiquitin-26S proteasome system mediated by Mdm2 or the human papilloma virus E6 protein. Here we show that COP9 signalosome (CSN)-specific phosphorylation targets human p53 to ubiquitin-26S proteasome-dependent degradation. As visualized by electron microscopy, p53 binds with high affinity to the native CSN complex p53 interacts via its N-terminus with CSN subunit 5/Jab1 as shown by far-western and pull-down assays. The CSN-specific phosphorylation sites were mapped to the core domain of p53 including Thr155. A phosphorylated peptide, Ap53(l45-l64), specifically inhibits CSN- mediated phosphorylation and p53 degradation. Curcumin, a CSN kinase inhibitor, blocks E6-dependent p53 degradation in reticulocyte lysates. Mutation of Thr155 to valine is sufficient to stabilize p53 against E6-dependent degradation in reticutocyte lysates and to reduce binding to Mdm2. The p53T155V mutant accumulates in both HeLa and HL 60 cells and exhi- bits a mutant (PAb 240+) conformation. It induces the cyclin-dependent inhibitor p21. In HeLa and MCF-7 cells, inhibition of CSN kinase by curcumin or Δp53(145-164) results in accumulation of endogenous p53. [ABSTRACT FROM AUTHOR]

Treatment with Panax notoginseng saponin (PNS) can prevent neurological damage in middle cerebral artery occlusion model rats to promote recovery after a stroke. However, the exact molecular mechanisms are unknown and require further study. In the present study, mRNA sequencing was employed to investigate differential gene expression between model and sham groups, and between model and PNS‑treated groups. Enrichment of gene data was performed using Gene Ontology analysis and the Kyoto Encyclopedia of Genes and Genomes database. Hub genes were identified and networks were constructed using Cytoscape that were further verified by reverse transcription‑quantitative PCR. A total of 1,104 genes of interest were found, which included 690 upregulated and 414 downregulated genes that were identified when the model was compared with the sham group. Additionally, 817 genes of interest, which included 390 upregulated and 427 downregulated genes, were identified when the PNS‑treated group was compared with the model group. There were 303 overlapping genes of interest between the analysis of model to sham groups, and the analysis of model to PNS‑treated groups. The top 10 genes from the 303 aberrantly expressed genes of interest included ubiquitin conjugating enzyme E2 variant 2, small ubiquitin‑related modifier 1, small RNA binding exonuclease protection factor La, Finkel‑Biskis‑Reilly murine sarcoma virus (FBR‑MuSV) ubiquitously expressed, centrosomal protein 290 kDa, DNA‑directed RNA polymerase II subunit K, cullin‑4B, matrin‑3 and vascular endothelial growth factor receptor 2. In conclusion, these genes may be important in the underlying mechanism of PNS treatment in ischemic stroke. Additionally, the present data provided novel insight into the pathogenesis of ischemic stroke. [ABSTRACT FROM AUTHOR]

Tumor cells show acidic conditions compared with normal cells, which further inspires scientist to build nanocarrier responsive to tumor microenvironment (TME) for enhancing tumor therapeutic efficacy. Here, we report a pH-sensitive and biocompatible polyprodrug based on dextran-doxorubicin (DOX) prodrug (DOXDT) for enhanced chemotherapy. Highdensity DOX component was covalently decorated on the nanocarrier and the drug molecules could be effectively released in the acidic tumor tissue/cells, improving chemotherapy efficacy. Specifically, a dextran-based copolymer was preliminarily prepared by one-step atom transfer radical polymerization (ATRP); then DOX was conjugated on the copolymer component via pH-responsive hydrazone bond. The structure of DOXDT can be well-controlled. The resulting DOXDT was able to further self-assemble into nanoscale micelles with a hydration diameter of about 32.4 nm, which presented excellent micellar stability. Compared to lipid-based drug delivery system, the DOXDT prodrug showed higher drug load capacity up to 23.6%. In addition, excellent stability and smaller size of the nanocarrier contributed to better tissue permeability and tumor suppressive effects in vivo. Hence, this amphipathic DOXDT prodrug is promising in the development of translational DOX formulations, which would be widely applied in cancer therapy. [ABSTRACT FROM AUTHOR]