Plasma interleukin-17 and alpha-fetoprotein combination effectively predicts imminent hepatocellular carcinoma occurrence in liver cirrhotic patients.

BACKGROUND: Predicting imminent hepatocellular carcinoma (HCC) in liver cirrhotic patients is an unmet medical need. We aimed to investigate circulatory biomarkers and their optimum combinations in a prospective study. METHODS: We investigated plasma interleukin 17 (IL-17) concentrations, quantified using enzyme-linked immunosorbent assay (ELISA), for the prediction of HCC in a large cohort of 404 HCC-naïve liver cirrhotic patients regularly followed after recruitment. Additionally, IL-17 in surgically resected tumor tissues were evaluated using immunohistochemistry staining. RESULTS: IL-17 was detected in HCC tissues. The IL-17 concentrations in the peripheral blood do not have correlation with an extensive list of 31 common demographic, metabolic and liver function variables in the cohort of liver cirrhotic patients. Furthermore, patients stratified by IL-17 and alpha-fetoprotein (AFP) showed distinctive cumulative incidence of HCC. Imminent HCC, defined here as HCC occurrence within 1 year, can be predicted by IL-17 alone with an area under the receiver operating characteristic curve [AUC] of 0.762 (P = 0.002). An multivariate analysis showed that age, hepatitis C viral infection, AFP and IL-17 were four independent factors associated with imminent HCC (adjusted P = 0.03, 0.041, 0.024 and 0.008 respectively). An explicit risk score (R) combining the concentrations of two plasma biomarkers, AFP and IL-17, achieved a high AUC of 0.933 (95% confidence interval 0.893-0.972, P < 0.001) in predicting imminent HCC, with 100% sensitivity and 79.9% specificity at the optimum cutoff. The score is defined as: [Formula: see text] CONCLUSIONS: The circulatory IL-17 concentration is a predictor of subsequent HCC occurrence in liver cirrhotic patients. The combination of AFP and IL-17 is highly effective in predicting imminent HCC within 1 year.

A new triterpenoid and other compounds from lichens Cryptothecia faveomaculata Makhija & Patw.

Ten compounds (1-10) were purified from the extract of lichens C. faveomaculata, and among these one new triterpenoid, cryptothecin A (1) was characterized through mass spectrometric and 2D NMR spectroscopic analyses. Some of the isolated compounds were assessed for their antimicrobial (1, 6, and 8) and cytotoxic activity (1, 4-5, and 7-9), but only weak inhibitory effects were observed.

High-performance quantum dot light-emitting diodes using chip-scale package structures with high reliability and wide color gamut for backlight displays.

High reliability and wide color gamut light-emitting diodes (LEDs) that use composite quantum dot films (CQDFs) protected by chip-scale package (CSP) structures are presented. CQDFs containing CdZnSeS/ZnS core-shell QDs and the K2SiF6:Mn4+ phosphors were mixed with silicone gel and used as color converters in the CSP QD-LEDs. The CSP QD-LEDs, used for backlight displays, transmitted through a color filter and exhibited ITU-R Recommendation BT.2020 of approximately 86% (a National Television System Committee value of 115%). Furthermore, we performed a long-term reliability analysis test on the CSP QD-LEDs for 2352 h to verify whether the optical performance of CSP QD-LEDs does not significantly degrade relative to that of a conventional plastic leaded chip carrier QD-LEDs. We implemented a highly reliable package technology that can protect the QDs, solve the moisture/oxygen problems in defective QD-LEDs, and produce a backlight source for display with a wide color gamut.

Mesoporous Silica Particles Integrated with All-Inorganic CsPbBr3 Perovskite Quantum-Dot Nanocomposites (MP-PQDs) with High Stability and Wide Color Gamut Used for Backlight Display.

All-inorganic CsPbX3 (X=I, Br, Cl) perovskite quantum dots (PQDs) have been investigated because of their optical properties, such as tunable wavelength, narrow band, and high quantum efficiency. These features have been used in light emitting diode (LED) devices. LED on-chip fabrication uses mixed green and red quantum dots with silicone gel. However, the ion-exchange effect widens the narrow emission spectrum. Quantum dots cannot be mixed because of anion exchange. We address this issue with a mesoporous PQD nanocomposite that can prevent ion exchange and increase stability. We mixed green quantum-dot-containing mesoporous silica nanocomposites with red PQDs, which can prevent the anion-exchange effect and increase thermal and photo stability. We applied the new PQD-based LEDs for backlight displays. We also used PQDs in an on-chip LED device. Our white LED device for backlight display passed through a color filter with an NTSC value of 113 % and Rec. 2020 of 85 %.

Efficient Preparation of Site-Specific Antibody-Drug Conjugates Using Phosphopantetheinyl Transferases.

Post-translational modification catalyzed by phosphopantetheinyl transferases (PPTases) has previously been used to site-specifically label proteins with structurally diverse molecules. PPTase catalysis results in covalent modification of a serine residue in acyl/peptidyl carrier proteins and their surrogate substrates which are typically fused to the N- or C-terminus. To test the utility of PPTases for preparing antibody-drug conjugates (ADCs), we inserted 11 and 12-mer PPTase substrate sequences at 110 constant region loop positions of trastuzumab. Using Sfp-PPTase, 63 sites could be efficiently labeled with an auristatin toxin, resulting in 95 homogeneous ADCs. ADCs labeled in the CH1 domain displayed in general excellent pharmacokinetic profiles and negligible drug loss. A subset of CH2 domain conjugates underwent rapid clearance in mouse pharmacokinetic studies. Rapid clearance correlated with lower thermal stability of the particular antibodies. Independent of conjugation site, almost all ADCs exhibited subnanomolar in vitro cytotoxicity against HER2-positive cell lines. One selected ADC was shown to induce tumor regression in a xenograft model at a single dose of 3 mg/kg, demonstrating that PPTase-mediated conjugation is suitable for the production of highly efficacious and homogeneous ADCs.

Reactions of Tp(NH[double bond, length as m-dash]CPh(2))(PPh(3))Ru-Cl with HC[triple bond, length as m-dash]CPh in the presence of H(2)O: insertion/hydration products.

The reaction of benzophenone imine complex (NH[double bond, length as m-dash]CPh(2))[Ru]Cl {[Ru] = Tp(PPh(3))Ru; Tp = HB(pz)(3), pz = pyrazolyl} with HC[triple bond, length as m-dash]CPh in the presence of H(2)O afforded the cis-alkynyl(vinylidene) complex [Ru](C[triple bond, length as m-dash]CPh)([double bond, length as m-dash]C[double bond, length as m-dash]CHPh) , as well as two alkenyl ketone regioisomers [Ru]C(CH(2)Ph)[double bond, length as m-dash]CHC(O)Ph and [Ru]C(Ph)[double bond, length as m-dash]CHC(O)CH(2)Ph . The combination of insertion and hydration process resulted in the unprecedented formation of the alkenyl ketone complexes.

(Benzonitrile-κN)chlorido[hydrido-tris(pyrazol-1-yl-κN)borato](triphenyl-phosphine-κP)ruthenium(II) ethanol solvate.

The reaction of [Ru(C(9)H(10)BN(6))Cl(C(18)H(15)P)(2)] with benzo-nitrile leads to crystals of the title compound, [Ru(C(9)H(10)BN(6))Cl(C(18)H(15)P)(C(7)H(5)N)]·C(2)H(5)OH. In the crystal structure, the environment about the ruthenium metal center corresponds to a slightly distorted octa-hedron with an average N-Ru-N bite angle of the Tp ligand of 86.6 (2)°.

Erratum: (Benzonitrile-κN)chlorido[hydrido-tris(pyrazol-1-yl-κN)borato](triphenyl-phosphine-κP)ruthenium(II) ethanol solvate. Corrigendum.

The author list in the paper by Tong, Hung, Wang, Lin & Lo [Acta Cryst. (2009), E65, m438] is corrected.[This corrects the article DOI: 10.1107/S1600536809010265.].

(O,O'-Diethyl dithio-phosphato-κS,S')(hydridotripyrazol-1-ylborato-κN,N,N)(triphenyl-phosphine-κP)ruthenium(II).

Reaction of [Ru(Tp)Cl(PPh(3))(2)] {where Tp is hydridotri-pyrazol-yl-borate, BH[C(3)H(3)N(2))(3))]} with NH(4)[S(2)P(OEt)(2)] in methanol afforded the title compound, [Ru(C(9)H(10)BN(6))(C(4)H(10)O(2)PS(2))(C(18)H(15)P)], in which the Ru(II) ion is in a slightly disorted octa-hedral coordination environment. The [S(2)P(OEt)(2)](-) ligand coordinates in a chelating mode with two similar Ru-S bond lengths and a slightly acute S-Ru-S angle. The atoms of both -OCH(2)CH(3) groups of the diethyl dithio-phosphate ligand are disordered over two sites with approximate occupancies of 0.76 and 0.24.

(Benzophenone imine-κN)-chlorido(hydrido-tripyrazolyl-borato)-(triphenyl-phosphine)ruthenium(II) diethyl ether solvate.

The reaction of RuCl(Tp)(Ph(3)P)(2), where Tp is [(CH)(3)N(2)](3)BH, with benzophenone imine leads to the formation of the title compound, [Ru(C(9)H(10)BN(6))Cl(C(13)H(11)N)(C(18)H(15)P)]·C(4)H(10)O. The environment about the Ru atom corresponds to a slightly distorted octa-hedron and the bite angle of the Tp ligand produces an average N-Ru-N angle of 86.3 (9)°. The three Ru-N(Tp) bond lengths [2.117 (2), 2.079 (2) and 2.084 (2) Å] are slightly longer than the average distance (2.038 Å) in other ruthenium-Tp complexes.

Azido-(1,1-diphenyl-methanimine-κN)[hydridotris(pyrazolyl-κN)borato](triphenyl-phosphine-κP)ruthenium(II) diethyl ether solvate.

The reaction of [RuCl(C(9)H(10)BN(6))(C(18)H(15)P)(2)] with benzo-phenone imine in methanol, in the presence of sodium azide, leads to the formation of the title compound, [Ru(C(9)H(10)BN(6))(N(3))(HN=CPh(2))(C(18)H(15)P)]·C(4)H(10)O, which crystallizes as the diethyl ether solvate. In the crystal structure, the Ru atom is coordinated by three N atoms of one hydridotris(pyrazoly)borate anion, one P atom of one triphenyl-phosphine ligand, one N atom of the azide anion and one N atom of the benzophenone-imine ligand in a slightly distorted octa-hedral geometry. The azide anion is almost linear [177.0 (5)°], with an Ru-N-N angle of 125.9 (3)°. There is a small difference between the N-N distances [1.200 (5) and 1.164 (5) Å], the longer bond being adjacent to the Ru atom.

(Dithio-benzoato-κS,S')[hydridotris(pyrazol-1-yl-κN)borato](triphenyl-phosphine-κP)ruthenium(II).

Reaction of [Ru(Tp)Cl(PPh(3))(2)] (Tp = hydridotrispyrazolyl-borate) with ammonium dithio-benzoate in methanol leads to the formation of the title compound, [Ru(C(9)H(10)BN(6))(C(7)H(5)S(2))(C(18)H(15)P)]. In the crystal structure, the Ru atom is coordinated by three N atoms of the Tp ligand, one P atom of the triphenyl-phosphine ligand and the two S atoms of the dithio-benzoate ligand within a slightly distorted octa-hedron. The Ru-S bonds are slightly different [2.321 (1) and 2.396 (1) Å] and the average N-Ru-N angle is 86.31°.

Methyl-ene bis-(dithio-benzoate).

In the title compound, C(15)H(12)S(4), two phenyl-dithio-carboxyl-ate units are linked through a methyl-ene C atom on a twofold rotation axis. The central S-CH(2)-S angle of 116.9 (5)° is significantly larger than the ideal tetra-hedral value. The dihedral angle formed by the two phenyl rings is 68.2 (1)°. The refined Flack parameter of 0.2 (3) does not permit unambiguous determination of the absolute structure.

A new method for removing endotoxin from plasma using hemocompatible affinity chromatography technology, applicable for extracorporeal treatment of septic patients.

The pathogenesis of sepsis begins with the proliferation of micro-organisms at a site of infection, followed by invasion of the bloodstream and other organs. Gram-negative bacteria account for a large part of sepsis cases. The structural component of Gram-negative bacteria, endotoxin or lipopolysaccharide (LPS), induces the synthesis and release of endogenous mediators of sepsis. A growing number of investigations of the molecular mechanisms occurring in sepsis, point to endotoxin as a central mediator leading to multi-organ failure and death. In numerous clinical trials, attempts to target molecules downstream of endotoxin have been made, but have not been associated with improved survival. We describe an affinity-based system for the selective removal of endotoxin from plasma. The small-scale device, a 1.5 ml cartridge, contains beads that bind endotoxin with high specificity and efficiency. In addition, evidence is presented that this device does not affect plasma hemostasis, nor does it activate the complement system. Taken together, these results represent a proof of principle for endotoxin removal from plasma, which may be of clinical value to treat sepsis by extracorporeal circulation of the blood through a scaled-up version of this endotoxin-removing device.

A nonsense mutation in exon 8 of the APC gene (Arg283Ter) causes clinically variable FAP in a Malaysian Chinese family.

The present study was carried out to characterize the causative genetic mutation in a medium-sized Malaysian Chinese pedigree of three generations affected with familial adenomatous polyposis (FAP). Clinical data and genetic studies revealed considerable phenotypic variability in affected individuals in this family. Blood was obtained from members of the FAP-01 family and genomic DNA was extracted. Mutation screening of the adenomatous polyposis coli (APC) gene was carried out using the single strand conformation polymorphism (SSCP) technique. The possibility of exon skipping was predicted by splicing motif recognition software (ESEfinder release2.0). SSCP results showed mobility shifts in exon 8 of the APC gene which segregated with affected members of the family. Sequence analysis revealed that the affected individuals are heterozygous for a C847T transition, whilst all the unaffected family members and control individuals are homozygous C at the same position. This nucleotide substitution generates a stop codon at amino acid position 283, in place of the usual arginine (Arg283Ter). We conclude that an Arg283Ter mutation in the APC gene is causative of the FAP phenotype in this family, although there is considerable variation in the presentation of this disease among affected individuals. Computational analysis predicts that this mutation occurs within sequences that may function as splicing signals, so that the sequence change may affect normal splicing.

Gonadal mosaicism of Frasier syndrome in 3 Chinese siblings with donor splice site mutation of Wilms' tumour gene.

Frasier syndrome is a rare human developmental disorder classically affecting 46,XY females and leading to male pseudohermaphroditism and chronic renal failure. We describe a family with both 46,XX and 46,XY females affected by the syndrome due to WT1 splice site mutations. The diagnosis of Frasier syndrome in 1 of the children led to the discovery of the syndrome in 2 other siblings, of whom 1 is asymptomatic. Since the mutation was not found in either parents, gonadal mosaicism was suggested. The implication of family screening for WT1 gene mutation in asymptomatic members is also discussed.