Osteosarcoma (OS) is the most common primary bone malignancy, mainly affecting children and adolescents. Currently, surgical resection combined with adjuvant chemotherapy has been standardized for OS treatment. Despite great advances in chemotherapy for OS, its clinical prognosis remains far from satisfactory; this is due to chemoresistance, which has become a major obstacle to improving OS treatment. Autophagy, a catabolic process through which cells eliminate and recycle their own damaged proteins and organelles to provide energy, can be activated by chemotherapeutic drugs. Accumulating evidence has indicated that autophagy plays the dual role in the regulation of OS chemoresistance by either promoting drug resistance or increasing drug sensitivity. The aim of the present review was to demonstrate thatautophagy has both a cytoprotective and an autophagic cell death function in OS chemoresistance. In addition, methods to detect autophagy, autophagy inducers and inhibitors, as well as autophagy-mediated metastasis, immunotherapy and clinical prognosis are also discussed. Contents 1. Introduction 2. Methods of detecting autophagy 3. Autophagy inducers and inhibitors 4. Dual role of autophagy in OS chemoresistance 5. Autophagy and metastasis 6. Autophagy and immunotherapy 7. Autophagy as a prognostic marker in OS 8. Conclusion

BackgroundXylose mother liquor has high concentrations of xylose (35%-40%) as well as other sugars such as L-arabinose (10%-15%), galactose (8%-10%), glucose (8%-10%), and other minor sugars. Due to the complexity of this mother liquor, further isolation of xylose by simple method is not possible. In China, more than 50,000 metric tons of xylose mother liquor was produced in 2009, and the management of sugars like xylose that present in the low-cost liquor is a problem.ResultsWe designed a novel strategy in which Bacillus subtilis and Candida maltosa were combined and used to convert xylose in this mother liquor to xylitol, a product of higher value. First, the xylose mother liquor was detoxified with the yeast C. maltosa to remove furfural and 5-hydromethylfurfural (HMF), which are inhibitors of B. subtilis growth. The glucose present in the mother liquor was also depleted by this yeast, which was an added advantage because glucose causes carbon catabolite repression in B. subtilis. This detoxification treatment resulted in an inhibitor-free mother liquor, and the C. maltosa cells could be reused as biocatalysts at a later stage to reduce xylose to xylitol. In the second step, a recombinant B. subtilis strain with a disrupted xylose isomerase gene was constructed. The detoxified xylose mother liquor was used as the medium for recombinant B. subtilis cultivation, and this led to L-arabinose depletion and xylose enrichment of the medium. In the third step, the xylose was further reduced to xylitol by C. maltosa cells, and crystallized xylitol was obtained from this yeast transformation medium. C. maltosa transformation of the xylose-enriched medium resulted in xylitol with 4.25 g L-1·h-1 volumetric productivity and 0.85 g xylitol/g xylose specific productivity.ConclusionIn this study, we developed a biological method for the purification of xylose from xylose mother liquor and subsequent preparation of xylitol by C. maltosa-mediated biohydrogenation of xylose.

Objective: Smad7 is an inhibitory Smad and plays a protective role in many inflammatory diseases. However, the roles of Smad7 in rheumatoid arthritis (RA) remain unexplored, which were investigated in this study.Methods: The activation of TGF-β/Smad signaling was examined in synovial tissues of patients with RA. The functional roles and mechanisms of Smad7 in RA were determined in a mouse model of collagen-induced arthritis (CIA) in Smad7 wild-type (WT) and knockout (KO) CD-1 mice, a strain resistant to autoimmune arthritis induction.Results: TGF-β/Smad3 signaling was markedly activated in synovial tissues of patients with RA, which was associated with the loss of Smad7, and enhanced Th17 and Th1 immune response. The potential roles of Smad7 in RA were further investigated in a mouse model of CIA in Smad7 WT/KO CD-1 mice. As expected, Smad7-WT CD-1 mice did not develop CIA. Surprisingly, CD-1 mice with Smad7 deficiency developed severe arthritis including severe joint swelling, synovial hyperplasia, cartilage damage, massive infiltration of CD3+ T cells and F4/80+ macrophages, and upregulation of proinflammatory cytokines IL-1β, TNFα, and MCP-1. Further studies revealed that enhanced arthritis in Smad7 KO CD-1 mice was associated with increased Th1, Th2 and, importantly, Th17 over the Treg immune response with overactive TGF-β/Smad3 and proinflammatory IL-6 signaling in the joint tissues.Conclusions: Smad7 deficiency increases the susceptibility to autoimmune arthritis in CD-1 mice. Enhanced TGF-β/Smad3-IL-6 signaling and Th17 immune response may be a mechanism through which disrupted Smad7 causes autoimmune arthritis in CD-1 mice.

The plant cuticle, which consists of cutin and waxes, forms a hydrophobic coating covering the aerial surfaces of all plants. It acts as an interface between plants and their surrounding environment whilst also protecting them against biotic and abiotic stresses. In this research, we have investigated the biodiversity and cuticle properties of aquatic plant duckweed, using samples isolated from four different locations around Hongze lake in Jiangsu province, China. The samples were genotyped using two chloroplast markers and nuclear ribosomal DNA markers, which revealed them as ecotypes of the larger duckweed, Spirodela polyrhiza. Duckweed cuticle properties were investigated by compositional analysis using Gas Chromatography coupled with Mass Spectroscopy (GC-MS) Flame Ionization Detector (GC-FID), and ultrastructural observation by cryo-Scanning Electron Microscopy (cryo-SEM). Cuticle compositional analysis indicated that fatty acids and primary alcohols, the two typical constituents found in many land plant cuticle, are the major duckweed wax components. A large portion of the duckweed wax fraction is composed of phytosterols, represented by campesterol, stigmasterol, sitosterol and their common precursor squalene. The cryo-SEM observation uncovered significant differences between the surface structures of the top air-facing and bottom water-facing sides of the plant fronds. The top side of the fronds, containing multiple stomata complexes, appeared to be represented by a rather flat waxy film sporadically covered with wax crystals. Underneath the waxy film was detected a barely distinguished nanoridge net, which became distinctly noticeable after chloroform treatment. On the bottom side of the fronds, the large epidermal cells were covered by the well-structured net, whose sections became narrower and sharper under cryo-SEM following chloroform treatment. These structural differences between the abaxial and adaxial sides of the fronds evidently relate to their distinct physiological roles in interacting with the contrasting environments of sunlight/air and nutrients/water. The unique structural and biochemical features of Spirodela frond surfaces with their rapid reproductive cycle and readily availability genome sequence, make duckweed an attractive monocot model for studying the fundamental processes related to plant protection against ultraviolet irradiation, pathogens and other environmental stresses.

BackgroundL-arabinose is an important intermediate for anti-virus drug synthesis and has also been used in food additives for diets-controlling in recent years. Commercial production of L-arabinose is a complex progress consisting of acid hydrolysis of gum arabic, followed by multiple procedures of purification, thus making high production cost. Therefore, there is a biotechnological and commercial interest in the development of new cost-effective and high-performance methods for obtaining high purity grade L-arabinose.ResultsAn alternative, economical method for purifying L-arabinose from xylose mother liquor was developed in this study. After screening 306 yeast strains, a strain of Pichia anomala Y161 was selected as it could effectively metabolize other sugars but not L-arabinose. Fermentation in a medium containing xylose mother liquor permitted enrichment of L-arabinose by a significant depletion of other sugars. Biochemical analysis of this yeast strain confirmed that its poor capacity for utilizing L-arabinose was due to low activities of the enzymes required for the metabolism of this sugar. Response surface methodology was employed for optimization the fermentation conditions in shake flask cultures. The optimum conditions were: 75 h fermentation time, at 32.5°C, in a medium containing 21% (v/v) xylose mother liquor. Under these conditions, the highest purity of L-arabinose reached was 86.1% of total sugar, facilitating recovery of white crystalline L-arabinose from the fermentation medium by simple methods.ConclusionYeast-mediated biopurification provides a dynamic method to prepare high purity of L-arabinose from the feedstock solution xylose mother liqour, with cost-effective and high-performance properties.