Irinotecan hydrochloride liposome HR070803 in combination with 5-fluorouracil and leucovorin in locally advanced or metastatic pancreatic ductal adenocarcinoma following prior gemcitabine-based therapy (PAN-HEROIC-1): a phase 3 trial.

Liposomal irinotecan has shown promising antitumor activity in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) who have undergone prior gemcitabine-based therapies. This randomized, double-blind, parallel-controlled, multicenter phase 3 study (NCT05074589) assessed the efficacy and safety of liposomal irinotecan HR070803 combined with 5-fluorouracil (5-FU) and leucovorin (LV) in this patient population. Patients with unresectable, locally advanced, or metastatic PDAC who had previously received gemcitabine-based therapies were randomized 1:1 to receive either HR070803 (60 mg/m2 anhydrous irinotecan hydrochloride, equal to 56.5 mg/m2 free base) or placebo, both in combination with 5-FU (2000 mg/m2) and LV (200 mg/m2), all given intravenously every two weeks. The primary endpoint of the study was overall survival (OS). A total of 298 patients were enrolled and received HR070803 plus 5-FU/LV (HR070803 group, n = 149) or placebo plus 5-FU/LV (placebo group, n = 149). Median OS was significantly improved in the HR070803 group compared to the placebo group (7.4 months [95% CI 6.1-8.4] versus 5.0 months [95% CI 4.3-6.0]; HR 0.63 [95% CI 0.48-0.84]; two-sided p = 0.0019). The most common grade ≥ 3 adverse events in the HR070803 group were increased gamma-glutamyltransferase (19.0% versus 11.6% in placebo group) and decreased neutrophil count (12.9% versus 0 in placebo group). No treatment-related deaths occurred in the HR070803 group, while the placebo group reported one treatment-related death (abdominal infection). HR070803 in combination with 5-FU/LV has shown promising efficacy and manageable safety in advanced or metastatic PDAC in the second-line setting, representing a potential option in this patient population.

Extraction and characterisation of hemicelluloses from maize stem.

INTRODUCTION: Extraction and characterisation of hemicelluloses are very important for converting them into functional materials and chemicals. OBJECTIVE: To develop a method for isolation of hemicelluloses from all cell walls. METHODOLOGY: Sequential steps using 90% dioxane, 80% acidic dioxane, 100% dimethyl sulphoxide and 8% NaOH were used for extraction of the hemicellulosic preparations (H(1), H(2), H(3) and H(4)) from maize stem. Advanced NMR techniques were used for the analysis of native hemicelluloses. RESULTS: Hemicelluloses with high yieldd were isolated from all cell walls, and contained arabinoxylan as the major polysaccharide. H(3) was substituted by α-L-arabinofuranose, α-D-xylopyranose, and acetyl groups (degree of saturation = 0.12/0.09) at O-3/O-2 of xylan. H(4) had a long continuous side chain of arabinose residues, and associated closely with non-cellulosic glucose. The hemicelluloses formed more linkages with guaiacyl lignins, and some p-coumaric acids built a bridge between hemicelluloses and lignin in maize stem. CONCLUSION: This modified method is successful for the isolation of hemicelluloses with high yields from all cell walls of maize stem.

Combined Therapeutic Effects of 131I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer.

BACKGROUND: Owing to its combined effects, the co-delivery of different therapeutics is a promising option for the treatment of cancer. In the present study, tumor-targeting poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) nanoparticles were developed for the transportation of two molecules, namely chemotherapeutic drug 5-fluorouracil (5Fu) and radionuclide iodine-131 (131I), in a single platform. METHODS: The obtained nanoparticles (Cetuximab [Cet]-PEG-PLA-5Fu-131I) were spherical (diameter approximately 110 nm) and pH-sensitive. The targeting effect of nanoparticles via Cet was confirmed in colorectal cancer cells using a fluorescent assay. The combined effects of Cet-PEG-PLA-5Fu-131I on cell viability and apoptosis were evaluated in colorectal cancer cells by Cell Counting Kit-8 and flow cytometry assays. RESULTS: Blank nanoparticles (Cet-PEG-PLA) showed good biocompatibility, and Cet-PEG-PLA-5Fu-131I nanoparticles were the most effective in terms of inhibition of cell viability and induction of apoptosis compared with monotherapy using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-131I. In the xenograft mouse model, compared with using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-131I alone, Cet-PEG-PLA-5Fu-131I nanoparticles exhibited prolonged circulation in the blood and accumulation in the tumor, thus resulting in enhanced antitumor efficacy. Additionally, combined radio-chemotherapy with Cet-PEG-PLA-5Fu-131I nanoparticles was associated with smaller tumor sizes than monotherapy, revealing the superior antitumor effects of Cet-PEG-PLA-5Fu-131I nanoparticles. These effects were further evidenced by histological and immunohistochemical analyses. CONCLUSION: The multifunctional Cet-PEG-PLA-5Fu-131I nanoparticles are promising candidates for the co-delivery of 5Fu-mediated chemotherapy and 131I-mediated radiotherapy.

Superadsorbent hydrogel based on lignin and montmorillonite for Cu(II) ions removal from aqueous solution.

Superadsorbent hydrogel was prepared from lignin and montmorillonite for Cu(II) ions removal, and the chemical structure and morphology of the hydrogel were characterized by FT-IR, XRD, SEM and XPS. The swelling kinetics of the prepared hydrogel was investigated, and the result showed that the swelling process fit the Schott second-order dynamic equation. The influences of pH, contact time, Na+ concentration, and initial Cu(II) ion concentration on adsorption were studied, and the maximum adsorption value was 1.17 mmol/g, and the adsorption was rapid during the initial 5 h period, and copper ions adsorption on the superadsorbent hydrogel is a favorable process. The results also indicated that the adsorption kinetics was in accordance with the pseudo-second-order kinetic model and the adsorption isotherm conformed to the Freundlich model. FT-IR and XPS analysis revealed that the adsorption behavior was mainly due to ion exchange. The desorption ratios of copper ions from the superadsorbent were >0.8, and the regeneration efficiency was >80% after five cycles reuse, and the results show the excellent desorption performance and reusability of the prepared hydrogel.

Extraction and characterization of original lignin and hemicelluloses from wheat straw.

Original lignin and hemicelluloses were sequentially extracted with high yield/purity, using acidic dioxane/water solution and dimethyl sulfoxide, from ball-milled wheat straw. The acidic dioxane lignin fraction is distinguished by high beta-O-4' structures and by low amounts of condensed units (beta-5', 5-5', and beta-1'). Hemicelluloses contain arabinoxylans as the major polysaccharides, which are substituted by alpha-l-arabinofuranose, 4-O-methylglucuronic acid, acetyl group (DS = 0.1), and xylose at O-3 and/or O-2 of xylans. It was found that arabinoxylans form cross-links with lignins through ferulates via ether bonds, glucuronic acid via ester bonds, and arbinose/xylose via both ether and glycosidic bonds, respectively, in the cell walls of wheat straw. Diferulates are also incorporated into cross-links between lignin and hemicelluloses as well as lignification of wheat straw cell walls. The guaiacyl unit is considered to be a significant condensed structural constructor in extracted lignin and a connector between lignin and carbohydrates.

Preparation and adsorption property of xylan/poly(acrylic acid) magnetic nanocomposite hydrogel adsorbent.

Adsorbents based on natural polysaccharides have attracted increasing interest because of their low-cost and biodegradability, particularly, polysaccharide-based nanocomposite adsorbents. In this study the xylan/poly(acrylic acid) magnetic nanocomposite hydrogel adsorbent was prepared from wheat straw xylan and Fe3O4 nanoparticles, and its adsorption property was studied on methylene blue removal. The prepared hydrogel adsorbent had a semi-interpenetrating network structure and exhibited a macro-porous structure with interconnected porous channels. Super-paramagnetic characteristic behavior was observed from magnetic analysis using a vibrating sample magnetometer. The optimum condition for methylene blue adsorption on the adsorbent was found at pH 8 with an adsorbent dosage of 3g/L and an initial concentration of 400mg/L, and the removal percentage reached above 90%. The adsorption isotherm of methylene blue on the prepared hydrogel adsorbent was fitted to the Langmuir model, and the pseudo-second-order kinetic model could describe the adsorption process. All obtained results indicated that the prepared hydrogel adsorbent is promising for water treatment applications.

Selective conversion of cotton cellulose to glucose and 5-hydroxymethyl furfural with SO4(2-)/MxOy solid superacid catalyst.

This paper presented a mild hydrothermal process for degradation of cotton cellulose with solid superacid catalyst and selective conversion of cotton cellulose to glucose and 5-hydroxymethyl furfural (HMF). Five kinds of solid superacid catalyst such as SO4(2-)/SnO2, SO4(2-)/TiO2, SO4(2-)/ZrO2, SO4(2-)/Fe2O3 and SO4(2-)/Al2O3 were prepared by impregnation method. The BET surface area of catalyst SO4(2-)/SnO2 was up to 118.8m(2)g(-1) when impregnation was performed with 1molL(-1) H2SO4 of impregnating solution at 550°C calcination temperature for 3h. It made the hydrothermal temperature of cellulose degradation decrease to 190°C successfully and suppressed the side reaction. The NH3-TPD profile of SO4(2-)/SnO2 indicated there was a wide region of stronger acid sites on the catalyst surface. The depolymerization of cotton cellulose obtained 11.0% yield and 22.0% selectivity of HMF and 26.8% yield and 53.4% selectivity of glucose, respectively. The regeneration and reuse of solid superacid catalyst were also discussed in this paper.

Multiple turnovers of DNAzyme for amplified detection of ATP and reduced thiol in cell homogenates.

A conveniently amplified DNAzyme-based fluorescence strategy was designed for highly sensitive detection of ATP or reduced thiol based on the introduction of an ATP aptamer or a disulfide bond in the bioconjugates of magnetic nanoparticles (MNP) and polystyrene microsphere-DNAzyme complexes (PSM-DNAzyme).

Fractional and physico-chemical characterization of hemicelluloses from ultrasonic irradiated sugarcane bagasse.

The present study was undertaken to investigate the extractability of the hemicelluloses from bagasse obtained by ultrasound-assisted extraction methods. The results showed that the ultrasonic treatment and sequential extractions with alkali and alkaline peroxide under the conditions given led to a release of over 90% of the original hemicelluloses and lignin. This fact as well as the sugar composition and structural features of the isolated seven hemicellulosic fractions indicated that ultrasonication attacked the integrity of cell walls, cleaved the ether linkages between lignin and hemicelluloses, and increased accessibility and extractability of the hemicelluloses. Increasing alkali concentration from 0.5 to 2M and alkaline peroxide percentage from 0.5% to 3.0% resulted in degradation of hemicellulosic backbone as shown by a decrease in their molecular weights from 43,580 to 14,470 and 30,180 to 18,130gmol(-1), respectively. However, there were no significant differences in the structural features of the seven sequential alkali- or alkaline peroxide-soluble hemicellulosic fractions, which are composed mainly of L-arabino-(4-O-methyl-D-glucurono)-D-xylans. Ferulic and p-coumaric acids were found to be chemically linked with hemicelluloses.

Acetylation of rice straw with or without catalysts and its characterization as a natural sorbent in oil spill cleanup.

An investigation of the acetylation of rice straw with acetic anhydride at 100 and 120 degrees C for 1-4 h with four tertiary amine catalysts (pyridine, 4-dimethylaminopyridine, N-methylpyrrolidine, and N-methylpyrrolidinone) or without catalyst in a solvent-free system was undertaken, and the extent of acetylation was measured by weight percent gain, which increased with the extent of reaction time and temperature and the amounts of catalyst used. 4-Dimethylaminopyridine was found to be the most effective catalyst of those studied. At a concentration of 7% of the catalyst in acetic anhydride, a weight percent gain of 15.4% was realized, compared with 11.2% for the noncatalyst reaction, after 0.5 h of exposure to the system at 120 degrees C. Characterization of acetylated straw was performed by FT-IR, CP MAS (13)C NMR, and thermal studies. Interestingly, the acetylated straw is significantly hydrophobic and does not get wet with water, thereby offering potential for the better utilization of cheap waste materials as natural sorbents in oil cleanup.

Comparative study of crude and purified cellulose from wheat straw.

A sequential totally chlorine-free procedure for isolation of cellulose from wheat straw was proposed in this study. The dewaxed straw was pretreated with 0.5 M NaOH in 60% methanol at 60 degrees C for 2.5 h under ultrasonic irradiation for 0-35 min and sequentially posttreated with 2% H(2)O(2)-0.2% TAED at pH 11.8 for 12 h at 48 degrees C, which together solubilized 85.3-86.1% of the original hemicelluloses and 91.7-93.2% of the original lignin, respectively. The yield of crude cellulose ranged between 46.2 and 49.2% on a dry weight basis related to wheat straw, which contained 11.2-12.2% residual hemicelluloses and 2.5-2.9% remaining lignin. Further treatment of the corresponding crude cellulosic preparations with 80% acetic acid-70% nitric acid under the condition given yielded 36.8-37.7% of the purified cellulose, which contained minor amounts of bound hemicelluloses (2.5-2.8%) and was relatively free of associated lignin (0.1-0.2%). The isolated crude and purified cellulose samples were comparatively studied by FT-IR and CP/MAS (13)C NMR spectroscopy, and the relative crystallinity was also estimated. The final stage treatment with 80% acetic acid-70% nitric acid decreased the hemicelluloses and lignin associated in the crude cellulose but led to 3.1-5.4% degradation of the original cellulose; in addition, the purity of the obtained cellulose was high. However, it was found that the final stage treatment is not severe enough to cause decrystallization of cellulose. The thermal stability of the purified cellulose is higher than that of the corresponding crude cellulose.

Fractional isolation and physico-chemical characterization of hemicelluloses by a two-stage treatment from Haloxylon ammodendron and Elaeagnus angustifolia.

The cell wall material of Chinese shrubs Haloxylon ammodendron and Elaeagnus angustifolia was fractionated by successive extractions with ethanol/H(2)O (60:40, v/v) under acidic conditions (0.2 N HCl) at 70 degrees C for 4 h, and 2% H(2)O(2) at pH 11.5 for 16 h, respectively. The sequential two-step treatment resulted in the dissolution of 83.9% and 87.6% of the original hemicelluloses from dewaxed H. ammodendron and E. angustifolia, respectively. Xylose, glucose, and galactose were the major sugar constituents in the two acidic organosolv-soluble hemicellulosic preparations. The two alkaline peroxide-soluble hemicellulosic fractions were shown to be composed primarily of xylose, comprising over 80% of the total sugars. The results also showed that the two alkaline peroxide-soluble hemicellulosic fractions were more linear and acidic, and had higher molecular mass and thermal stability than the two acidic organosolv-soluble hemicellulosic preparations. The 2% H(2)O(2) posttreatment did not result in any significant changes in the macromolecular structure of the isolated hemicelluloses. It is probable that lignin protects hemicelluloses and cellulose from being attacked by peroxide.

Controllable regioselective enzymatic synthesis of polymerizable 5'-O-vinyl- and 3'-O-vinyl-nucleoside analogues in acetone.

An efficient synthesis of polymerizable 3'- and 5'-O-acyl-nucleoside derivatives has been developed from inosine and 2'-deoxyuridine by enzyme-catalyzed regioselective acylation with divinyl dicarboxylates. In acetone, Lipozyme (immobilized lipase from Mucor miehei) gave 5'-O-acyl-nucleoside products, and PPL (lipase from porcine pancreas) provided 3'-O-acyl-nucleoside products.