Since entering the Chinese market in 2015, Airbnb has become a major player in the Chinese home-sharing arena. This article uses data from 8012 active Airbnb listings in Shanghai and presents three models (linear regression, geographically weighted regression, and random forest) to study the determinants of Airbnb listing prices and incorporate geographic variation in price modeling. Results show that property quality plays a key role in shaping listing prices. Due to Airbnb’s distinctions from traditional lodging in both features and business models, Airbnb pricing determinants differ accordingly. For example, location conditions were found to have a limited impact in regions with established transportation networks. Among the three models, random forest performed best in terms of prediction accuracy. Lastly, practical implications are discussed.
sqv ( squashed vulva ) genes comprise a set of eight independent loci in Caenorhabditis elegans required zygotically for the invagination of vulval epithelial cells and maternally for normal oocyte formation and embryogenesis. Sequencing of sqv-3 , sqv-7 , and sqv-8 suggested a role for the encoded proteins in glycolipid or glycoprotein biosynthesis. Using a combination of in vitro analysis of SQV enzymatic activities, sqv + - mediated rescue of vertebrate cell lines, and biochemical characterization of sqv mutants, we show that sqv-3 , -7 , and -8 all affect the biosynthesis of glycosaminoglycans and therefore compromise the function of one specific class of glycoconjugates, proteoglycans. These findings establish the importance of proteoglycans and their associated glycosaminoglycans in epithelial morphogenesis and patterning during C. elegans development.
Hyaluronidase (Hyal) and low m.w. hyaluronan (LMW HA) fragments have been widely reported to stimulate the innate immune response. However, most hyaluronidases used were purified from animal tissues (e.g., bovine testis Hyal [BTH]), and contain endotoxin and other unrelated proteins. We tested a highly purified recombinant human Hyal (rHuPH20) and endotoxin-free HA fragments from M(r) 5,000 to 1,500,000 in the rodent air pouch model of inflammation to determine their potential for stimulation of the innate immune response. Exogenous LMW HA fragments (average M(r) 200,000) failed to induce either cytokine/chemokine production or neutrophil infiltration into the air pouch. Challenging the air pouch with LPS or BTH stimulated production of cytokines and chemokines but rHuPH20 did not, suggesting that neither PH20 nor generation of LMW HA fragments in situ stimulates cytokine and chemokine production. LPS and BTH also induced neutrophil infiltration into the air pouch, which was not observed with rHuPH20 treatment. Endotoxin-depleted BTH had much reduced proinflammatory activity, suggesting that the difference in inflammatory responses between rHuPH20 and BTH is likely due to endotoxin contaminants in BTH. When rHuPH20 was dosed with LPS, the induction of cytokines and chemokines was the same as LPS alone, but neutrophil infiltration was inhibited, likely by interrupting HA-CD44 interaction. Our results indicate that neither rHuPH20 nor its directly generated HA catabolites have inflammatory properties in the air pouch model, and rHuPH20 can instead inhibit some aspects of inflammation, such as neutrophil infiltration into the air pouch.
Acute pancreatitis (AP) is a common acute abdominal disease, 10-20% of which can evolve into severe AP (SAP) causing significant morbidity and mortality. Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential of repairing SAP, but the detailed mechanism remains unknown. We demonstrate here that microRNA-9 (miR-9) modified BMSCs (pri-miR-9-BMSCs) can significantly reduce the pancreatic edema, infiltration, hemorrhage, necrosis, the release of amylase and lipase. Meanwhile, decreased local/systemic inflammatory response (TNF-α↓, IL-1β↓, IL-6↓, HMGB1↓, MPO↓, CD68↓, IL-4↑, IL-10↑, and TGF-β↑) and enhanced regeneration of damaged pancreas (Reg4↑, PTF1↑, and PDX1↑) are also promoted. But these effects diminish or disappear after antagonizing miR-9 (TuD). Besides, we find that miR-9 is negatively correlated with AP and miR-9 agomir which can mimic the effects of pri-miR-9-BMSCs and protect injured pancreas. Furthermore, we investigate that BMSCs deliver miR-9 to the injured pancreas or peripheral blood mononuclear cell (PBMC), which can target the NF-κB1/p50 gene and inhibit the NF-κB signaling pathway (p-P65↓, NF-κB1/p50↓, IκBα↑, IκBβ↑). Taken together, these results show that miR-9 is a key paracrine factor of BMSCs attenuating SAP targeting the NF-κB1/p50 gene and suppressing the NF-κB signaling pathway.
Abstract The administration of mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs) to enhance tissue repair is currently undergoing clinical trials. Some studies, including our previous work, have also revealed the beneficial effect of MSCs in severe acute pancreatitis (SAP); however, their mechanisms or mode of action remain controversial. In this study, we demonstrated that intravenously (i.v.)-administered human MSCs (hMSCs) remarkably promoted recovery from experimental SAP without significant engraftment of hMSCs in the damaged pancreas. Interestingly, we found that i.v.-administered hMSCs with knockdown of TSG-6 expression lost most of their anti-inflammatory effects and thus could not significantly ameliorate SAP. As expected, the effects of hMSCs were also duplicated by i.v. infusion of recombinant TSG-6. Furthermore, our results showed that the increase of oxidative stress, activation of the NLRP3 inflammasome and NF- κ B signaling in SAP was substantially inhibited following administration of hMSCs or TSG-6, which was dependent on the presence of CD-44 receptors in acinar cells. In conclusion, our study, for the first time, revealed that novel mechanisms are responsible for the immunomodulatory effect of i.v. hMSCs.
Abstract Hyaluronan (HA), a nonsulfated glycosaminoglycan, is a significant component of the extracellular matrix of many solid tumors. HA accumulation has been correlated with local invasion, the presence of distal metastasis, higher tumor grade, and poorer overall survival. We have previously demonstrated that sustained HA removal, accomplished with a novel pegylated human recombinant hyaluronidase PH20 (PEGPH20), inhibited tumor growth and enhanced chemotherapeutic activity in HA-rich xenografts (Thompson et al, 2010). As endogenous lysosomal hyaluronidase expression has been implicated as a tumor promoter (Kovar et al, 2006), and exogenous hyaluronidase has been shown to act as a tumor suppressor (Shuster et al, 2002), we aimed to determine whether exogenous PEGPH20 administration alters the metastatic behavior of malignant cells in solid tumors. In a first set of experimental metastasis studies, HA-rich prostate PC3 (2e5) or breast MDA-MB-231 (1e5) cells were intracardially injected (IC) into nude mice (NCR nu/nu). Mice were subsequently treated (>20 min) with a single dose of PEGPH20 (4.5 mg/kg, IV) or vehicle and tumor seeding into organs tracked via bioluminescent imaging over time (n=8/group). In a second set of spontaneous metastasis experiments, prostate PC3 (2e6) or breast MDA-MB-231-Has2 (2e6) cells were injected into either the tibia periosteum or mammary fad pad of nude mice, respectively. MDA-MB-231-Has2 cells are a MDA-MB-231 Has 2 synthase overexpressing clone, shown to overexpress HA both in vitro and in vivo. When PC3 tumors reached ∼375 mm3 (n=11/group), and MDA-MB-231-Has2 reached ∼400 mm3 (n=6/group), mice received PEGPH20 (4.5 mg/kg, IV) or vehicle, q3d × 8 or q3d × 5, respectively. Mice were subsequently sacrificed and lymph node metastasis assessed histologically. Following the initial set of IC experiments, no significant difference in the number or frequency of metastatic nodules, as assessed by bioluminescence, was observed following PEGPH20 treatment versus control in either cell line (PC3, p=0.49; MDA-MB-231, p=0.89). In the second set of experiments, no difference in lymph node metastasis in either cell line was detected (PC3, p=0.68; MDA-MB-231, p=0.55). Finally, no histological evidence of increased metastases was observed in any organs examined (liver, kidney, heart, spleen or lung) following PEGPH20 administration in either study. Taken together, these results suggest exogenous PEGPH20 administration does not impact metastatic behavior in the PC3 prostate, MDA-MB-231 breast or MDA-MB-231-Has2 breast preclinical models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 442. doi:10.1158/1538-7445.AM2011-442
Objective To investigate the expression and activation of extracellular signal-regulated kinases (ERK) in lung cancer and its clinical significance.Methods Samples were obtained from 52 patients with nonsmall cell lung cancer.Western blot was used to detect the expression of ERK,ERK2 and P-ERK proteins.Immunohistochemistry was used for localization of ERK protein.Results The levels of ERK1,ERK2 and P-ERK proteins in nonsmall cell lung cancer tissues were increased,which were 1.5,1.8 and 1.7 times compared with those in adjacent normal tissues respectively,and they all had remarkable difference (P0.01).ERK1 and ERK2 were observed to be a positive linear correlation.Immunohistochemistry revealed that ERK proteins were mainly located in cytoplasm.Conclusion Over-expression of ERK may play an important role in the development of human nonsmall cell lung cancer.
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