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Four new monacolin analogs, monacolin T (1), monacolin U (2) 6a-O-methyl-4,6-dihydromonacolin L (3), and 6a-O-ethyl-4,6-dihydromonacolin L (4) were isolated from the ethanolic extract of Monascus purpureus-fermented rice. Their structures were determined by a combination of 1D, 2D NMR experiments ( 1 H- 1 HCOSY, HSQC, HMBC, and ROESY), and mass spectrometry. In vitro cytotoxic assay, all compounds were inactive at the concentration of 10 µM.

In this study, we originally aimed to characterize the potential role of Argonaute 2 (AGO2) in the nucleus, a key protein of the miRNA machinery. We combined Chromatin Immunoprecipitation (ChIP) with high throughput sequencing (ChIP-seq) and quantitative mass spectrometry (ChIP-MS) using the broadly used AGO2 11A9 antibody to determine interactions with chromatin and nuclear proteins. We found a previously described interaction between AGO2 and SWI/SNF on chromatin with ChIP-MS and observed enrichment at enhancers and transcription start sites using ChIP-seq. However, antibody specificity issues can produce misleading results for ChIP, RNA-seq and Mass spectrometry. Therefore, we developed a CRISPR/Cas9 engineered AGO2 -/- HEK293T cell line to validate our findings. ChIP-qPCR and immunoprecipitation combined with MS (IP-MS) showed that the 11A9 antibody associates with chromatin and SWI/SNF in the absence of AGO2. Furthermore, stoichiometry, IP-MS and co-IP analysis suggests a direct interaction of this antibody with SMARCC1, a component of the SWI/SNF complex. For this reason, particular care should be taken in performing and interpreting experiments in which the 11A9 antibody is used to study a nuclear role of AGO2.

The repugnatorial glands of millipedes release various defensive chemical secretions. Although varieties of such defensive secretions have been studied, none of them is protein or peptide. Herein, a novel factor Xa (FXa) inhibitor named joannsin was identified and characterised from repugnatorial glands of Prospirobolus joannsi. Joannsin is composed of 72 amino acid residues including six cysteines, which form three intra-molecular disulfide bridges. It is a member of Kunitz-type protease inhibitor family, members of which are also found in the secretory glands of other arthropods. Recombinant joannsin exhibited remarkable inhibitory activity against trypsin and FXa with a Ki of 182.7 ± 14.6 and 29.5 ± 4.7 nM, respectively. Joannsin showed strong anti-thrombosis functions in vitro and in vivo. Joannsin is the first peptide component in millipede repugnatorial glands to be identified and is a potential candidate and/or template for the development of anti-thrombotic agents. These results also indicated that there is Kunitz-type protease inhibitor toxin in millipede repugnatorial glands as in other arthropods secretory glands.

The present study was designed to investigate the antimalarial activity of synthetic hepcidin and its effect on cytokine secretion in mice infected with Plasmodium berghei. The mice were infected with P. berghei intravenously and treated with hepcidin according to 4-day suppression test and Rane's test. The serum levels of interleukins (IL-1β, IL-2, IL-6, IL-10, IL-12p70, and IL-17A), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the experimental mice were determined using a cytometric bead array (CBA) kit. The survival rate of the infected mice was also registered. Additionally, the serum iron, alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (BIL) were detected to evaluate liver functions. Hepcidin exerted direct anti-malarial function in vivo and increased survival rate in a dose-dependent manner. In addition, the secretion of T helper cell type 1 (Th1), Th2, and Th17 cytokines, TNF-α, and IFN-γ were inhibited by hepcidin. In conclusion, our results demonstrated that synthetic hepcidin exerts in vivo antimalarial activity and possesses anti-inflammatory function, which provides a basis for future design of new derivatives with ideal anti-malarial activity., (Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Genome-wide association studies have identified a great number of non-coding risk variants for colorectal cancer (CRC). To date, the majority of these variants have not been functionally studied. Identification of allele-specific transcription factor (TF) binding is of great importance to understand regulatory consequences of such variants. A recently developed proteome-wide analysis of disease-associated SNPs (PWAS) enables identification of TF-DNA interactions in an unbiased manner. Here we perform a large-scale PWAS study to comprehensively characterize TF-binding landscape that is associated with CRC, which identifies 731 allele-specific TF binding at 116 CRC risk loci. This screen identifies the A-allele of rs1800734 within the promoter region of MLH1 as perturbing the binding of TFAP4 and consequently increasing DCLK3 expression through a long-range interaction, which promotes cancer malignancy through enhancing expression of the genes related to epithelial-to-mesenchymal transition.

The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels of histone acetylation but also at distal elements characterized by low acetylation levels and binding of the hematopoietic transcription factors LYL1 and LMO2. In contrast, ERG, FLI1, TAL1, and RUNX1 bind at all AML1-ETO-occupied regulatory regions, including those of the AML1-ETO gene itself, suggesting their involvement in regulating AML1-ETO expression levels. While expression of AML1-ETO in myeloid differentiated induced pluripotent stem cells (iPSCs) induces leukemic characteristics, overexpression increases cell death. We find that expression of wild-type transcription factors RUNX1 and ERG in AML is required to prevent this oncogene overexpression. Together our results show that the interplay of the epigenome and transcription factors prevents apoptosis in t(8;21) AML cells., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Four new taraxastane-type triterpenoids acids 3β,22α-dihydroxy-20-taraxasten-30-oic acid (1), 3β-hydroxy-22-oxo-20-taraxasten-30-oic acid (2), 3-oxo-22α-hydroxy-20- taraxasten-30-oic acid (3), and 3β,19β-dihydroxy-20-taraxasten-30-oic acid (4) were isolated and characterized from Cirsium setosum (Willd.) MB. Their structures were determined by the combination of 1D and 2D NMR experiments ((1)H-(1)HCOSY, HSQC, HMBC and ROESY) and mass spectrometry. Compound 2 exhibited potent selective cytotoxicity against human ovarian cancer cell line A2780 with an IC50 value of 3.9 μM.

Psoriasis is histologically characterized by keratinocytes (KC) hyperproliferation, inflammation, and increased angiogenesis, but the pathological factor responsible for these symptoms is unknown. Here, a neuroendocrine peptide (prokineticin 2, PK2), is highly expressed in human and mouse psoriatic skins but no significant change in other autoimmune diseases, suggesting that PK2 is a psoriasis-specific factor. Bacterial products significantly up-regulated PK2, implying that infection induces PK2 over-expression. PK2 promoted KC and macrophage to produce interleukin-1 (IL-1), the central player of inflammation and psoriasis, which acts on adjacent fibroblast to induce inflammatory cascades and KC hyperproliferation. IL-1 feeds back on macrophages to induce PK2 production to perpetuate PK2-IL-1 positive feedback loop. PK2 also promoted angiogenesis, another psoriatic symptom. In mouse models, PK2 over-expression aggravated psoriasis while its knock-down inhibited pathological development. The results indicate that PK2 over-production perpetuates psoriatic symptoms by creating PK-2-IL-1 vicious loop. PK2 is a central player in psoriasis and a promising psoriasis-specific target., (Copyright © 2016. Published by Elsevier B.V.)

Scorpion venom is deemed to contain many toxic peptides as an important source of natural compounds. Out of the two hundred proteins identified in Mesobuthus martensii (M. martensii), only a few peptide toxins have been found so far. Herein, a combinational approach based upon RNA sequencing and Liquid chromatography-mass spectrometry/mass spectrometry (LC MS/MS) was employed to explore the venom peptides in M. martensii. A total of 153 proteins were identified from the scorpion venom, 26 previously known and 127 newly identified. Of the novel toxins, 97 proteins exhibited sequence similarities to known toxins, and 30 were never reported. Combining peptidomic and transcriptomic analyses, the peptide sequence of BmKKx1 was reannotated and four disulfide bridges were confirmed within it. In light of the comparison of conservation and variety of toxin amino acid sequences, highly conserved and variable regions were perceived in 24 toxins that were parts of two sodium channel and two potassium channel toxins families. Taking all of this evidences together, the peptidomic analysis on M. martensii indeed identified numerous novel scorpion peptides, expanded our knowledge towards the venom diversity, and afforded a set of pharmaceutical candidates., Competing Interests: The authors declare no conflict of interest.

Inadequate trophoblast invasion and increased trophoblast apoptosis cause serious pregnancy complications. Pleckstrin homology-like domain, family Α, member 2 (PHLDA2) has been linked to fetal size at birth and growth restriction in a number of studies. However, the impact of PHLDA2 on trophoblast function had not been studied previously, to the best of our knowledge. In the present study, immunofluorescence staining demonstrated that primary trophoblasts isolated from placental villous tissues were positive for cytokeratin 18 (CK18), vimentin and human placental lactogen (hPL). JEG-3 cells and primary trophoblasts were infected with lentivirus overexpressing PHLDA2. RT-qPCR and western blot analysis detected high levels of PHLDA2. A Cell Counting Kit-8 (CCK-8) assay showed that PHLDA2 overexpression inhibited trophoblast proliferation. In addition, PHLDA2 significantly induced apoptosis, as evidenced by Annexin V-FITC/propidium iodide (PI) and Hoechst staining, along with activation of Bax and caspase-3 and also decreased Bcl-2 expression. Further investigation showed that PHLDA2 effectively induced reactive oxygen species (ROS) generation, caused cytochrome c release from the mitochondria into the cytosol and decreased mitochondrial membrane potential. PHLDA2 likely induced apoptosis through the mitochondrial pathway. Wound healing and Transwell assays indicated that PHLDA2 overexpression efficiently suppressed cell migration and invasion. These data suggest that PHLDA2 plays an important role in the occurrence and development of pregnancy complications by promoting trophoblast apoptosis and suppressing cell invasion.

New therapeutic agents for Candida albicans vaginitis are urgently awaiting to be developed because of the increasing antibiotic resistance of C. albicans. Antimicrobial peptides (AMPs) are one of the most promising choices for next-generation antibiotics. In this study, novel peptides were designed based on snake venom antimicrobial peptide cathelicidin-BF to promote anti-C. albicans activity and decrease side-effects. The designing strategies include substitutions of charged or hydrophobic amino acid residues for noncharged polar residues to promote antimicrobial activity and insertion of a hydrophobic residue in the hydrophilic side of the helix structure to reduce hemolysis. A designed tryptophan and lysine/arginine-rich cationic peptide 4 (ZY13) (VKRWKKWRWKWKKWV-NH2) exhibited excellent antimicrobial activity against either common strain or clinical isolates of antibiotic-resistant C. albicans with little hemolysis. Peptide 4 showed significant therapeutic effects on vaginitis in mice induced by the infection of clinical antibiotic-resistant C. albicans. The approaches herein might be useful for designing of AMPs.

Defensins are one of the major families of antimicrobial peptides (AMPs), and have been reported from prokaryotic to eukaryotic kingdoms. But defensins are seldom found in amphibian which is a major resource of novel AMPs. A novel defensin-like AMP (defensin-TK) was isolated and characterized from skin secretions of the tree frog Theloderma kwangsiensis. The cDNA encoding defensin-TK precursor was cloned from the skin cDNA library of T. kwangsiensis. The deduced precursor of defensin-TK was composed of three domains, a signal peptide of 16 residues, a spacer peptide of 1 residues and a mature peptide of 42 residues. The mature peptide of defensin-TK shared the highest identity with the salamander (Cynops fudingensis) defensin CFBD-1. The six conserved cysteines which formed intramolecular disulfide bonds of defensins also exist in defensin-TK. Phylogenetic analysis indicated that defensin-TK was closely related to fish β-defensins. Defensin-TK showed potent and broad-spectrum antimicrobial activity. In addition, defensin-TK exerted a low hemolytic activity on human red cells. These results suggested defensin-TK might play an important role in defense the skin pathogenic microbes of tree frog T. kwangsiensis, and might be a promising candidate for development of novel antimicrobial agents., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Dengue infection during peripartum period, although rare in endemic regions, has challenged clinicians regarding its management, especially if a parturient woman experiences postpartum hemorrhage due to a classical risk factor of maternal bleeding., Case: A full-term pregnant Vietnamese woman was diagnosed with polyhydramnios and Dengue with warning signs (DWS). She was administered platelet transfusion prior to delivery and then gave birth to a healthy newborn. After active management of the third stage of labor, the patient suffered a postpartum hemorrhage which was caused by uterine atony and accompanied with thrombocytopenia. Therefore, we decided to administer uterotonic drugs and additionally transfuse platelets., Conclusion: We describe a case of postpartum hemorrhage caused by uterine atony and coinciding with Dengue infection during delivery period, which is a rare clinical entity. With timely detection and management, the patient was finally discharged without complications.

Preeclampsia (PE) is one of the most common hypertensive disorders and is a leading cause of morbidity and mortality for pregnant women and perinatal babies. Additionally, pleckstrin homology-like domain family A member 2 (PHLDA2) is associated with placental dysfunction. However, the effect of PHLDA2 on trophoblast cell proliferation, migration and invasion has not been investigated. In this study, 15 PE patients and 15 normal pregnant women were recruited and clinical characteristics were summarized. Pleckstrin homology-like domain family A member 2 levels in placental tissues were examined using real-time PCR and western blot. Overexpression plasmid and PHLDA2 siRNA was introduced into JEG-3 cells, respectively. Cell proliferation was measured using MTT assay and flow cytometry. Cell migration and invasion capacities were assessed by wound healing and Transwell assays. It was found that PE patients collectively presented proteinuria, elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP), and lower gestational ages and birth weights. Pleckstrin homology-like domain family A member 2 levels in the preeclamptic placenta were significantly upregulated. Pleckstrin homology-like domain family A member 2 overexpression significantly arrested cells in the G0/G1 phase, inhibited cell proliferation and suppressed the migration and invasion of JEG-3 cells. Pleckstrin homology-like domain family A member 2 knockdown significantly blocked the cells in the S phase of the cell cycle. Knockdown of PHLDA2 alleviated the inhibition on the migration and invasion of trophoblast cells JEG-3. These findings illustrate that PHLDA2 may participate in PE pathogenesis and indicate its potential application in the early diagnosis of PE., (© 2015 Wiley Publishing Asia Pty Ltd.)

Purpose: The authors aimed to develop 1 novel navigation-guided robotic system for craniofacial surgery to improve accuracy during operation., Materials and Methods: A new 7-DOF (7-degree-of-freedom) robotic arm was designed and manufactured. Based on our self-developed navigation system TBNAVIS-CMFS, the key technique of integration was studied. A phantom skull model was manufactured based on computed tomography image data and used for the preexperimental study. Firstly, virtual planning was achieved through the TBNAVIS-CMFS, where the Le Fort I procedure was executed through simulation. Then, the actual Le Fort 1 osteotomy was expected to perform with the use of the robotic arm following the instructions from the navigation system., Results: The theoretical prototype of navigation-guided robotic system for craniofacial surgery was established successfully, which performed the planned Le Fort I procedure with the whole process visible on the screen., Conclusions: The technical method of navigation-guided robotics system, allowing the operator to practice the virtual planning procedure through navigation system as well as perform the actual operation thru the robotic arm, could be regarded as a valuable option for benefiting craniofacial surgeons.

Various bio-active substances in amphibian skins play important roles in survival of the amphibians. Many protease inhibitor peptides have been identified from amphibian skins, which are supposed to negatively modulate the activity of proteases to avoid premature degradation or release of skin peptides, or to inhibit extracellular proteases produced by invading bacteria. However, there is no information on the proteinase inhibitors from the frog Lepidobatrachus laevis which is unique in South America. In this work, a cDNA encoding a novel trypsin inhibitor-like (TIL) cysteine-rich peptide was identified from the skin cDNA library of L. laevis. The 240-bp coding region encodes an 80-amino acid residue precursor protein containing 10 half-cysteines. By sequence comparison and signal peptide prediction, the precursor was predicted to release a 55-amino acid mature peptide with amino acid sequence, IRCPKDKIYKFCGSPCPPSCKDLTPNCIAVCKKGCFCRDGTVDNNHGKCVKKENC. The mature peptide was named LL-TIL. LL-TIL shares significant domain similarity with the peptides from the TIL supper family. Antimicrobial and trypsin-inhibitory abilities of recombinant LL-TIL were tested. Recombinant LL-TIL showed no antimicrobial activity, while it had trypsin-inhibiting activity with a Ki of 16.5178 μM. These results suggested there was TIL peptide with proteinase-inhibiting activity in the skin of frog L. laevis. To the best of our knowledge, this is the first report of TIL peptide from frog skin.

Patent urachus is a rare congenital abnormality. Since its first description by Cabriolus in 1550, few cases have been reported. A 26-year-old Vietnamese primigravida presented at 20 weeks of gestation for evaluation of a cystic mass in the umbilical cord, which was first discovered at week 13 of pregnancy by ultrasound scan. The cystic mass originated from the root of the umbilical cord, connected to the urinary bladder, and no intestinal contents were enclosed within. Doppler ultrasound assessment showed that the single umbilical artery existed within the normal range. The progression of the umbilical cyst continued to be screened, but the mass disappeared on ultrasound images at 27 weeks of gestation. This led to the consideration of the cyst's rupture. After 38 gestational weeks, the pregnant woman delivered a 3350g male infant via cesarean section because of an obstructed vaginal labor. The following days, a stream of urine was recorded leaking out from the umbilical mass whenever he cried. Seven weeks after delivery, an open surgical approach was successfully performed. The baby is now 43 months of age, growing and developing normally. Since an allantoic cyst with patent urachus is a rare clinical entity, early discovery, close monitoring and accurate diagnosis through ultrasound in the prenatal period may consequently allow clinicians to have suitable attitudes towards management when the infant is born.

To solve the phase matching and analyte filling problems in the microstructured optical fiber (MOF)-based surface plasmon resonance (SPR) sensors, we present the D-shaped hollow core MOF-based SPR sensor. The air hole in the fiber core can lower the refractive index of a Gaussian-like core mode to match with that of a plasmon mode. The analyte is deposited directly onto the D-shaped flat surface instead of filling the fiber holes. We numerically investigate the effect of the air hole in the core on the SPR sensing performance, and identify the sensor sensitivity on wavelength, amplitude and phase. This work allows us to determine the feasibility of using the D-shaped hollow-core MOFs to develop a high-sensitivity, real-time and distributed SPR sensor.

Interactions between transcription factors and genomic DNA, and in particular their impact on disease and cell fate, have been extensively studied on a global level using techniques based on next-generation sequencing. These approaches, however, do not allow an unbiased study of protein complexes that bind to certain DNA sequences. DNA pulldowns from crude lysates combined with quantitative mass spectrometry were recently introduced to close this gap. Established protocols, however, are restricted to cell lines because they are based on metabolic labeling or require large amounts of material. We introduce a high-throughput-compatible DNA pulldown that combines on-bead digestion with direct dimethyl labeling or label-free protein quantification. We demonstrate that our method can efficiently identify transcription factors binding to their consensus DNA motifs in extracts from primary foreskin fibroblasts and peripheral blood mononuclear cells (PBMCs) freshly isolated from human donors. Nuclear proteomes with absolute quantification of nearly 7000 proteins in K562 cells and PBMCs clearly link differential interactions to differences in protein abundance, hence stressing the importance of selecting relevant cell extracts for any interaction in question. As shown for rs6904029, a SNP highly associated with chronic lymphocytic leukemia, our approach can provide invaluable functional data, for example, through integration with GWAS.

We propose a temperature sensor design based on surface plasmon resonances (SPRs) supported by filling the holes of a six-hole photonic crystal fiber (PCF) with a silver nanowire. A liquid mixture (ethanol and chloroform) with a large thermo-optic coefficient is filled into the PCF holes as sensing medium. The filled silver nanowires can support resonance peaks and the peak will shift when temperature variations induce changes in the refractive indices of the mixture. By measuring the peak shift, the temperature change can be detected. The resonance peak is extremely sensitive to temperature because the refractive index of the filled mixture is close to that of the PCF material. Our numerical results indicate that a temperature sensitivity as high as 4 nm/K can be achieved and that the most sensitive range of the sensor can be tuned by changing the volume ratios of ethanol and chloroform. Moreover, the maximal sensitivity is relatively stable with random filled nanowires, which will be very convenient for the sensor fabrication.

A rare germline duplication upstream of the bone morphogenetic protein antagonist GREM1 causes a Mendelian-dominant predisposition to colorectal cancer (CRC). The underlying disease mechanism is strong, ectopic GREM1 overexpression in the intestinal epithelium. Here, we confirm that a common GREM1 polymorphism, rs16969681, is also associated with CRC susceptibility, conferring ∼20% differential risk in the general population. We hypothesized the underlying cause to be moderate differences in GREM1 expression. We showed that rs16969681 lies in a region of active chromatin with allele- and tissue-specific enhancer activity. The CRC high-risk allele was associated with stronger gene expression, and higher Grem1 mRNA levels increased the intestinal tumor burden in Apc(Min) mice. The intestine-specific transcription factor CDX2 and Wnt effector TCF7L2 bound near rs16969681, with significantly higher affinity for the risk allele, and CDX2 overexpression in CDX2/GREM1-negative cells caused re-expression of GREM1. rs16969681 influences CRC risk through effects on Wnt-driven GREM1 expression in colorectal tumors., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Establishment of noninvasive and efficient islet transplantation site together with the avoidance of immunosuppressive drugs for islet engraftment is currently the two major tasks for islet transplantation approach to treat patients with type 1 diabetes. Here, we proposed a method to achieve long-term allogeneic islet graft function without immunosuppression after transplantation in subcutaneous sites. Two agarose rods with basic fibroblast growth factor and heparin were implanted for 1 week in dorsal subcutaneous sites in diabetic rats. After rod removal, 1500 islets were transplanted into the prevascularized pockets. Islets transplanted in prevascularized but not nontreated subcutaneous sites rapidly reverted hyperglycemia in all streptozotocin-induced diabetic rats. In contrast to transient normalization of blood glucose when allogeneic islets were transplanted into liver, allogeneic islets transplanted into this prevascularized subcutaneous site demonstrated long-term graft survival and function in all three rat strain combinations (Fisher 344 to ACI, Lewis to ACI and Fisher 344 to Wistar), evidenced by nonfasting blood glucose level, plasma insulin concentration, intraperitoneal glucose tolerance test and immunohistochemistry. These results indicated that a subcutaneous site prevascularized by this method is potentially a suitable site for successful allogeneic islet transplantation without immunosuppression., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Crizotinib is an oral tyrosine kinase inhibitor approved for treating patients with non-small cell lung cancer (NSCLC) containing an anaplastic lymphoma kinase (ALK) rearrangement. We used knockout mice to study the roles of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) in plasma pharmacokinetics and brain accumulation of oral crizotinib, and the feasibility of improving crizotinib kinetics using coadministration of the dual ABCB1/ABCG2 inhibitor elacridar. In vitro, crizotinib was a good transport substrate of human ABCB1, but not of human ABCG2 or murine Abcg2. With low-dose oral crizotinib (5 mg/kg), Abcb1a/1b(-/-) and Abcb1a/1b;Abcg2(-/-) mice had an approximately twofold higher plasma AUC than wild-type mice, and a markedly (~40-fold) higher brain accumulation at 24 hr. Also at 4 hr, crizotinib brain concentrations were ∼25-fold, and brain-to-plasma ratios ~14-fold higher in Abcb1a/1b(-/-) and Abcb1a/1b;Abcg2(-/-) mice than in wild-type mice. High-dose oral crizotinib (50 mg/kg) resulted in comparable plasma pharmacokinetics between wild-type and Abcb1a/1b(-/-) mice, suggesting saturation of intestinal Abcb1. Nonetheless, brain accumulation at 24 hr was still ~70-fold higher in Abcb1a/1b(-/-) than in wild-type mice. Importantly, oral elacridar coadministration increased the plasma and brain concentrations and brain-to-plasma ratios of crizotinib in wild-type mice, equaling the levels in Abcb1a/1b;Abcg2(-/-) mice. Our results indicate that crizotinib oral availability and brain accumulation were primarily restricted by Abcb1 at a non-saturating dose, and that coadministration of elacridar with crizotinib could substantially increase crizotinib oral availability and delivery to the brain. This principle might be used to enhance therapeutic efficacy of crizotinib against brain metastases in NSCLC patients., (© 2013 UICC.)

In this paper, a reflective photonic crystal fiber (PCF) sensor probe for temperature measurement has been demonstrated both theoretically and experimentally. The performance of the device depends on the intensity modulation of the optical signal by liquid mixtures infiltrated into the air holes of commercial LMA-8 PCFs. The effective mode field area and the confinement loss of the probe are both proved highly temperature-dependent based on the finite element method (FEM). The experimental results show that the reflected power exhibits a linear response with a temperature sensitivity of about 1 dB/°C. The sensor probe presents a tunable temperature sensitive range due to the concentration of the mixture components. Further research illustrates that with appropriate mixtures of liquids, the probe could be developed as a cryogenic temperature sensor. The temperature sensitivity is about 0.75 dB/°C. Such a configuration is promising for a portable, low-power and all-in-fiber device for temperature or refractive index monitoring in chemical or biosensing applications.

Amorphous alloys structurally deviate from crystalline materials in that they possess unique short-range ordered and long-range disordered atomic arrangement. They are important catalytic materials due to their unique chemical and structural properties including broadly adjustable composition, structural homogeneity, and high concentration of coordinatively unsaturated sites. As chemically reduced metal-metalloid amorphous alloys exhibit excellent catalytic performance in applications such as efficient chemical production, energy conversion, and environmental remediation, there is an intense surge in interest in using them as catalytic materials. This critical review summarizes the progress in the study of the metal-metalloid amorphous alloy catalysts, mainly in recent decades, with special focus on their synthetic strategies and catalytic applications in petrochemical, fine chemical, energy, and environmental relevant reactions. The review is intended to be a valuable resource to researchers interested in these exciting catalytic materials. We concluded the review with some perspectives on the challenges and opportunities about the future developments of metal-metalloid amorphous alloy catalysts.

A quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay for the ALK inhibitor crizotinib was developed and validated. Plasma samples were pre-treated using protein precipitation with acetonitrile containing crizotinib-(13)C(2)-(2)H(5) as internal standard. The extract was directly injected into the chromatographic system after dilution with water. This system consisted of a sub-2 μm particle, trifunctional bonded octadecyl silica column with a gradient using 0.1% (v/v) of ammonium hydroxide in water and methanol. The eluate was transferred into the electrospray interface with positive ionization and the analyte was detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was validated in a 10-10,000 ng/ml calibration range with r(2)=0.99980±0.00014 for double logarithmic linear regression (n=5). Within day precisions (n=6) were 3.4-4.8%, between day (3 days; n=18) precisions 3.6-4.9%. Accuracies were between 107% and 112% for the whole calibration range. The drug was sufficiently stable under all relevant analytical conditions. Oxidative metabolites of crizotinib were monitored semi-quantitatively. Finally, the assay was successfully used to assess drug pharmacokinetics in mice., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Investigate the specific antitumor mechanism of SOCS1 silent DC vaccine and discuss the prospect of RNAi in the gene therapy for laryngocarcinoma in order to provide novel ideas of DCs clinical applications., Method: Dendritic cells derived from peripheral blood monocytes were cultured in vitro in the presence of GM-CSF, IL-4 and TNF-alpha. The morphological feature of DC was observed with inverted microscope. RNAi vector were transfected into DC. The expression of SOCS1 protein was detected with Western blot. The effective target sequences of siRNA against SOCS1 were screened out. The surface markers of mature DC, including CD83, CD86 and HLA-DR, were detected with flow cytometry. The concentration of IFN-gamma in the supernatant was assayed by ELISA. The proliferative ability of T cell stimulated by DC and the specific killing activity of cytotoxic T lymphocyte (CTL) induced by DC were evaluated by MTT assay., Result: Dendritic cells were obtained successfully. The RNAi vector was proved to be right by sequencing. The expression of SOCS1 decreased significantly under the influence of the 5th interference sequence. SOCS1 silent dendritic cells which were loaded with Hep-2 antigen had high expressions of CD83 (85.61 +/- 0.96)%, CD86 (96.86 +/- 1.20)% and HLA-DR (98.02 +/- 0.94)%. It could also stimulate the proliferation of T cells effectively as well as could increase the production of IFN-gamma, eventually enhanced the specific killing effect of CTL. The killing activity was more higher than that in control group when the effect cells and target cells were mixed up at the ratio of 50:1 (P < 0.01)., Conclusion: SOCS1 silent DC vaccines which were loaded with Hep-2 antigen could induce effective and specific anti-laryngocarcinoma immune responses.

One unusual aromatic monacolin analog, monacophenyl, was isolated from the ethanolic extract of Monascus purpureus-fermented rice. Its structure was completely and unambiguously assigned by one- and two-dimensional NMR techniques ((1)H NMR, (13)C NMR, HSQC, HMBC and NOESY) and high-resolution ESI-MS spectrometry., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: To study the extraction technology of flavonoids from Cynomorium songaricum by supercritical CO2 extraction., Methods: The effects of pressure, temperature, time, concentration of alcohol, dosage of chemical preparation, flux of CO2 and particle size were studied by single factor analysis and orthogonal test., Results: The optimized conditions were as follows: particle size 60 - 80 sieve mesh, the pressure was 30 MPa, the temperature was 50 degrees C, the time was 75 min, concentration of alcohol was 50%, entrainment rate was 8%, flux of CO2 was 5 mL/min. The total flavonoids yield could reach 21.18% under the above conditions., Conclusion: This method is simple, rapid and higher extraction yield, so it is suitable for the extraction of flavonoids from Cynomorium songaricum.

Column, thin-layer and gel chromatography have been compared as methods for the analysis of glycerol esters. It was found that gel chromatography gave much easier and faster analyses of monoglyceride emulsifiers, while at the same time providing a satisfactory distribution of fractions and giving an accuracy of determination corresponding to that of the standard method for their analysis.