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The former hydrogel released the drugs very slowly, while the latter hydrogel demonstrated zero order releasing kinetics optimal for drug delivery. In the in vivo wound healing testing on rats, both polysaccharide hydrogels improved the healing process mediated by the mentioned biomolecules. Sunitinib cost The tripeptide applied in the hydrogels showed significantly higher healing degree and lower healing time than in the control animals without treatment and when it was applied in an aqueous solution. Despite the absence of a synergistic effect, the mixture of the tripeptide and α-l-arginine in the hydrogels was also quite effective in wound healing. According to histological analysis, complete healing was achieved only when using the tripeptide in the flaxseed gum hydrogel. These observations might have an important prospect in clinical application of polysaccharide hydrogels.Grifola frondosa polysaccharides, especially β-glucans, showed the significant antitumor, hypoglycemic, and immune-stimulating activities. In the present study, a predominant regulatory subunit gfRho1p of β-1,3-glucan synthase in G. frondosa was identified with a molecular weight of 20.79 kDa and coded by a putative 648-bp small GTPase gene gfRho1. By constructing mutants of RNA interference and over-expression gfRho1, the roles of gfRho1 in the growth, cell wall integrity and polysaccharide biosynthesis were well investigated. The results revealed that defects of gfRho1 slowed mycelial growth rate by 22% to 33%, reduced mycelial polysaccharide and exo-polysaccharide yields by 4% to 7%, increased sensitivity to cell wall stress, and down-regulated gene transcriptions related to PKC-MAPK signaling pathway in cell wall integrity. Over-expression of gfRho1 improved mycelial growth rate and polysaccharide production of G. frondosa. Our study supports that gfRho1 is an essential regulator for polysaccharide biosynthesis, cell growth, cell wall integrity and stress response in G. frondosa.As one of the most promising biopolymers for a variety of potential applications, chitosan has attracted much attention because of its unique biological, chemical, and physical properties. The functionalization of chitosan has been adopted to synthesize novel chitosan derivatives with improved water-solubility and excellent biological activities. In this paper, chitosan was functionalized with a triphenylphosphonium group by means of the copper (I) catalyzed azide-alkyne "click" reaction and has been investigated as potential polymer for agricultural antifungal biomaterial. The influence of chemical modification on the structural characteristics and water-solubility of chitosan was investigated by FTIR spectroscopy, 1H NMR spectroscopy, elemental analysis, and UV-vis spectrum. Furthermore, the antifungal property of target chitosan derivative against four plant threatening fungal pathogens was evaluated and in vitro investigation demonstrated that triphenylphosphonium salt incorporated chitosan backbone had excellent antifungal property compared with chitosan and intermediate chitosan derivative. Notably, target chitosan derivative displayed relatively strongest antifungal effect with over 80% inhibitory index against Botrytis cinerea at 1.0 mg/mL. The results of a detailed antifungal study indicated that cationic chitosan derivative bearing 1,2,3-triazole and triphenylphosphonium moieties provided a promising platform for preparation of novel cationic antifungal biomaterials in the field of agriculture.Cutaneous wounds frequently require the use of patches to promote healing, nevertheless, most commercial products are fabricated with non-biodegradable synthetic substrates that pose environmental problems upon disposal. Herein, the partnership between two biobased nanofibrous polymers, namely a polysaccharide (nanofibrillated cellulose (NFC)) and a protein (lysozyme nanofibers (LNFs)), is explored to design sustainable fibrous patches with good mechanical performance and biological functionalities for wound healing applications. Two patches with different morphologies were prepared by vacuum filtration of a water-based suspension of both nanofibers and by sequential filtration of the separated suspensions (layered patch). The resultant freestanding patches exhibited high thermal stability (up to 250 °C), mechanical performance (Young's modulus ≥3.7 GPa), and UV-barrier properties. The combination of the bioactive LNFs with the mechanically robust NFC conveyed antioxidant activity (76-79% DPPH scavenging) and antimicrobial activity against Staphylococcus aureus (3.5-log CFU mL-1 reduction), which is a major benefit to prevent microbial wound infections. Moreover, these patches are biocompatible towards L929 fibroblast cells, and the in vitro wound healing assay evidenced a good migration capacity leading to an almost complete wound occlusion. Therefore, the partnership between the two naturally derived nanofibrous polymers represents a potential blueprint to engineer sustainable multifunctional patches for cutaneous wound healing.Cryogel materials are composed of porous and lightweight structures that can be used for many industrial applications, particularly, in agriculture for the controlled release of Tebuconazole fungicide. Accordingly, we prepared environmentally friendly cryogel using natural polymers such hydroxyethyl cellulose (HEC) and bacterial cellulose (BC). The cryogel was formed by blending aqueous solutions of both HEC and BC, which was then crosslinked with glyoxal and the mixture was underwent to drying using freeze drying technique. Different concentrations of the as prepared silver@titanium oxide nanoparticles (Ag@TiO2NPs) were incorporated within the cryogel formation in order to increase its antimicrobial efficiency. A mode pesticide Tebuconazole was encapsulated in the cryogel platform in order to control the release of Tebuconazole. Thus, the developed cryogel which was porous, cheap and had an antimicrobial effect, controlled pesticide release suggesting that it is a potential candidate for agricultural applications.The YbfF esterase family, which has a bifurcated binding pocket for diverse ligands, could serve as excellent biocatalysts in industrial and biotechnological applications. Here, the identification, characterization, and immobilization of a novel YbfF esterase (YbfFHalomonas elongata) from Halomonas elongata DSM 2581 is reported. Biochemical characterization of YbfF was carried out using activity staining, chromatographic analysis, kinetic analysis, activity assay, acetic acid release, and pH-indicator-based hydrolysis. YbfFH.elongata displayed broad substrate specificity, including that for p-nitrophenyl esters, glucose pentaacetate, tert-butyl acetate, and β-lactam-containing compounds, with high efficiency. Based on a homology model of YbfFH.elongata, Trp237 in the substrate-binding pocket, a critical residue for catalytic activity and substrate specificity was identified and characterized. Furthermore, crosslinked enzyme aggregates and nanoflower formation were explored to enhance the chemical stability and recyclability of YbfFH.elongata. The present study is the first report of a YbfF esterase from extremophiles, and explains its protein stability, catalytic activity, substrate specificities and diversities, kinetics, functional residues, amyloid formation, and immobilization.

Proton beam radiotherapy (PBT) has recently been applied to treat hepatocellular carcinoma (HCC); however, there is no randomized controlled trial-based evidence on its safety and efficacy. We compared the outcomes of PBT and radiofrequency ablation (RFA) in patients with recurrent/residual HCC (rHCC) in a phase III non-inferiority trial.

Patients with rHCC (size <3 cm, number ≤2) were randomly assigned to receive PBT or RFA according to Child-Pugh score and tumor stage. After randomization, if the assigned treatment was technically infeasible, crossover was allowed. The primary endpoint was 2-year local progression-free survival (LPFS), with a non-inferiority margin of 15% in the per-protocol (PP) population; a complementary analysis was performed in the intention-to-treat (ITT) population (NCT01963429).

The ITT population comprised 144 patients receiving either PBT (n= 72) or RFA (n= 72). Six patients switched from the PBT arm to the RFA arm and 19 patients switched from the RFA arm to the PBT arm. randomized controlled trial to evaluate the clinical outcomes of proton beam radiotherapy vs. radiofrequency ablation in patients with recurrent small HCC. Our findings show that this new technique is not inferior and can be applied safely in patients with small recurrent hepatocellular carcinoma.

Radiofrequency ablation is the standard of care for patients with small hepatocellular carcinoma in whom surgery is not feasible. This study is the first phase III randomized controlled trial to evaluate the clinical outcomes of proton beam radiotherapy vs. radiofrequency ablation in patients with recurrent small HCC. Our findings show that this new technique is not inferior and can be applied safely in patients with small recurrent hepatocellular carcinoma.

There are currently limited therapeutic options for hepatocellular carcinoma (HCC), particularly when it is diagnosed at advanced stages. Herein, we examined the pathophysiological role of ROS1 and assessed the utility of ROS1-targeted therapy for the treatment of HCC.

Recombinant ribonucleases (RNases) were purified, and the ligand-receptor relationship between RNase7 and ROS1 was validated in HCC cell lines by Duolink, immunofluorescence, and immunoprecipitation assays. Potential interacting residues between ROS1 and RNase7 were predicted using a protein-protein docking approach. The oncogenic function of RNase7 was analyzed by cell proliferation, migration and invasion assays, and a xenograft mouse model. The efficacy of anti-ROS1 inhibitor treatment was evaluated in patient-derived xenograft (PDX) and orthotopic models. Two independent patient cohorts were analyzed to evaluate the pathological relevance of RNase7/ROS1.

RNase7 associated with ROS1's N3-P2 domain and promoted ROS1-mediated oncogenic tith hepatocellular carcinoma and high RNase7 levels.

Receptor tyrosine kinases are known to be involved in tumorigenesis and have been targeted therapeutically for a number of cancers, including hepatocellular carcinoma. ROS1 is the only such receptor with kinase activity whose ligand has not been identified. Herein, we show that RNase7 acts as a ligand to activate ROS1 signaling. This has important pathophysiological and therapeutic implications. Anti-ROS1 inhibitors could be used to treatment patients with hepatocellular carcinoma and high RNase7 levels.Green revolution has boosted crop yields by the development of varieties which rely on high fertilizer application. Since then, higher productivity has largely witnessed excessive nitrogen (N) fertilizer application resulting in many environmentally and agronomically unsustainable consequences. One possible solution to this problem is to develop varieties with efficient N use endowed with genetically superior N metabolizing machinery, thereby significantly reducing N loss in soil and facilitating gainful yield performance at lower N conditions. Nitrate (NO3-) is the major form of N acquired by plants in aerobic soils. Hence, its efficient acquisition, transport, assimilation into complex organic compounds, and overall homeostasis is crucial to ensure productivity under optimal and suboptimal N conditions. Transcription factors are prime regulators of these processes, and insights into their mechanism of action and the resultant effect on N metabolism are crucial to generating crops with efficient and durable nitrogen use efficiency.