Obesity is a common chronic metabolic disease that is harmful to human health and predisposes the affected individuals to a cluster of pathologies. Insulin resistance (IR) is one of the most frequent complications of obesity. Hydroxytyrosol (HT) may reduce obesity and IR in high-fat diet (HFD)-fed mice; however, the mechanism underlying is still unknown. Systemic low-grade inflammation and intestinal dysfunction are thought to be associated with obesity and IR. In this study, we found that HFD feeding for 8 weeks altered the intestinal microbiota, injured intestinal barrier function, increased endotoxin release into the blood, enhanced the expression of inflammatory factors (TNF-α, IL-1β, IL-6) and lipid accumulation in liver, caused obesity, and aggravated IR via the JNK/IRS (Ser 307) pathway in HFD mice. We also found that HT gavage could reverse those effects and the beneficial effects of HT were transferable through fecal microbiota transplantation. Our data indicate that HT can improve obesity and IR by altering the composition of the intestinal microbiota and improving integrity of the intestinal wall. We propose that HT replenishment may be used as a dietary intervention strategy to prevent obesity and IR.

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BackgroundHypoxia is a striking feature of most solid tumors and could be used to discriminate tumors from normoxic tissues. Therefore, the design of hypoxia-conditioned Chimeric Antigen Receptor (CAR) T cells is a promising strategy to reduce on-target off-tumor toxicity in adoptive cell therapy. However, existing hypoxia-conditioned CAR-T designs have been only partially successful in enhancing safety profile but accompanied with reduced cytotoxic efficacy. Our goal is to further improve safety profile with retained excellent antitumor efficacy.MethodsIn this study, we designed and constructed a hypoxia-inducible transcription amplification system (HiTA-system) to control the expression of CAR in T (HiTA-CAR-T) cells. CAR expression was determined by Flow cytometry, and the activation and cytotoxicity of HiTA-CAR-T cells in vitro were evaluated in response to antigenic stimulations under hypoxic or normoxic conditions. The safety of HiTA-CAR-T cells was profiled in a mouse model for its on-target toxicity to normal liver and other tissues, and antitumor efficacy in vivo was monitored in murine xenograft models.ResultsOur results showed that HiTA-CAR-T cells are highly restricted to hypoxia for their CAR expression, activation and cytotoxicity to tumor cells in vitro. In a mouse model in vivo, HiTA-CAR-T cells targeting Her2 antigen showed undetectable CAR expression in all different normoxic tissues including human Her2-expresing liver, accordingly, no liver and systemic toxicity were observed; In contrast, regular CAR-T cells targeting Her2 displayed significant toxicity on human Her2-expression liver. Importantly, HiTA-CAR-T cells were able to achieve significant tumor suppression in murine xenograft models.ConclusionOur HiTA system showed a remarkable improvement in hypoxia-restricted transgene expression in comparison with currently available systems. HiTA-CAR-T cells presented significant antitumor activities in absence of any significant liver or systemic toxicity in vivo. This approach could be also applied to design CAR-T cell targeting other tumor antigens.

Mobile applications based on geospatial data are nowadays extensively used to support people's daily activities. Despite the potential overlap among nearby users' geospatial data demands, it has not been feasible to share geospatial data with peer wireless devices directly. To address this issue, we designed a scheme based on vector tiles to organize spatial data and proposed a system named GeoTile for geospatial data caching and sharing. In GeoTile, a tile request from the mobile client relies on multihop communication over intermediate nodes to reach the server. Since GeoTile enables all network nodes to cache and process geospatial data tiles, requests may be handled before they actually reach the server. We implement the GeoTile prototype system and conduct comprehensive real-world experiments to evaluate the performance. e result shows that the GeoTile system can serve vector tiles for users conveniently and friendly. In addition, the caching mechanism based on vector tiles can substantially reduce the response time and network throughput under the wireless multihop scenarios.

Boron nitride nanosheets (BNN) were prepared by molten hydroxide-assisted liquid exfoliation from hexagonal boron nitride powder with an effectively high yield, and then modified with hexachlorocyclotriphosphazene (HCCP) to obtain HCCP-BNN. The series of samples were applied to prepare flame-retardant cotton fabrics with the impregnation-drying method, and successful treatment was confirmed by scanning electron microscopy. The combustion performance of the as-prepared cotton fabrics was tested and evaluated. After coating with HCCP-BNN, the combustion rate of the fabric is reduced in vertical and horizontal combustion conditions and the limiting oxygen-index value of cotton fabric increases to 24.1, becoming less flammable than the blank cotton. The fibrous structure of the BNN and HCCP-BNN coated fabrics is relatively complete after combustion, which indicates that BNN have a certain protective effect on the fabric. The results demonstrate HCCP-BNN as an effective flame-retardant for cotton fabrics.