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Probiotics were found to be effective in ameliorating the microbial dysbiosis and inflammation caused by intestinal pathogens. However, biological challenges encountered during oral delivery have greatly limited their potential health benefits. Here, a model probiotic (Lactobacillus rhamnosus) was encapsulated in an intestinal-targeted hydrogel to alleviate bacterial enteritis in a novel mode. The hydrogel was prepared simply by the self-cross-linking of thiolated hyaluronic acid. Upon exposure to H 2 S which were excreted by surrounding intestinal pathogens, the hydrogel can locally degrade and rapidly release cargos to compete with source pathogens in turn for binding to the host. The mechanical properties of hydrogel were studied by rheological analysis, and the ideal stability was achieved at a polymer concentration of 4% (w/v). The morphology of the optimal encapsulation system was further measured by a scanning electron microscope, exhibiting uniform payload of probiotics. Endurance experiments indicated that the encapsulation of L. rhamnosus significantly enhanced their viability under gastrointestinal tract insults. Compared with free cells, encapsulated L. rhamnosus exerted better therapeutic effect against Salmonella-induced enteritis with negligible toxicity in vivo. These results demonstrate that this redox-responsive hydrogel may be a promising encapsulation and delivery system for improving the efficacy of orally administered probiotics.

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In the context of uneven development studies of China, urban built-up area changes are the index of the impact of power, as the local government is the only party that is able to acquire agricultural land and convert it to construction urban land. Existing studies generally use statistical data to describe the built-up area changes and struggle to meet the requirement of an updated and inexpensive monitoring of uneven development, especially for western cities with tight budgets. Open access NPP-VIIRS (Suomi National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite), NDVI (Normalized Difference Vegetation Index), and nighttime LST (Land Surface Temperature) data ranging from 2015 to 2019 were analyzed with a stratified SVM (Support Vector Machine) method in this study to track urban built-up area changes in Chengdu, one of the biggest cities in Western China. The SDE (Standard Deviation Ellipse) and Moran’s I were then applied to evaluate the spatial variations of the built-up area changes. It was revealed that the spatial evolution of built-up area change in Chengdu over the period 2015–2019 demonstrated a “northwest-southeast” spatial expansion pattern, and the change distance in the center of gravity in 2018 and 2019 was greater than that from 2015 to 2017, which reflected the faster uneven development in 2018 and 2019 in Chengdu. The results were verified with finer resolution Landsat-8 OLI images; the high OA (all larger than 92%) and KAPPA (all larger than 0.6) values showed the accuracy of the method. The methodology proposed in this study offers a practical way for cities with tight budgets to monitor uneven development, and this study suggests a further adaption using higher-resolution remote sensing images and field experiments.

Insights into the conformational organization and dynamics of proteins complexes at membranes is essential for our mechanistic understanding of numerous key biological processes. Here, we introduce graphene-induced energy transfer (GIET) to probe axial orientation of arrested macromolecules at lipid monolayers. Based on a calibrated distance-dependent efficiency within a dynamic range of 25 nm, we analyzed the conformational organization of proteins and complexes involved in tethering and fusion at the lysosome-like yeast vacuole. We observed that the membrane-anchored Rab7-like GTPase Ypt7 shows conformational reorganization upon interactions with effector proteins. Ensemble and time-resolved single-molecule GIET experiments revealed that the HOPS tethering complex, when recruited via Ypt7 to membranes, is dynamically alternating between a ‘closed’ and an ‘open’ conformation, with the latter possibly interacting with incoming vesicles. Our work highlights GIET as a unique spectroscopic ruler to reveal the axial orientation and dynamics of macromolecular complexes at biological membranes with sub-nanometer resolution.

Because the elongation of telomeres has been associated with tumorigenesis, it is of great interest to develop rapid and high-confidence telomerase activity detection methods for disease diagnosis. Currently, amplification-based strategies have been extensively explored for telomerase detection in vitro and in vivo. However, amplification is typically associated with poor reproducibility and high background, which hamper further applications of the strategies, particularly for real sample assays. Here, we demonstrate a new amplification-free single molecule imaging method for telomerase activity detection in vitro based on nucleic acid stochastic binding with total internal reflection fluorescence microscopy. The dynamic stochastic binding of a short fluorescent DNA probe with a genuine target yields a distinct kinetic signature from the background noise, allowing us to identify telomerase reaction products (TRPs) at the single molecule level. A limit-of-detection as low as 0.5 fM and a dynamic range of 0.5-500 fM for TRP detection were readily achieved. With this method, telomerase extracted from cancer cells was determined with sensitivity down to 10 cells. Moreover, the length distribution of TRPs was also determined by multiple stochastic probing, which could provide deep insight into the mechanistic study of telomerase catalysis.

After an osteosarcoma excision, recurrence and bone defects are significant challenges for clinicians. In this study, the curcumin (Cur) loaded chitosan (CS) nanoparticles (CCNP) encapsulated silk fibroin (SF)/hyaluronic acid esterified by methacrylate (HAMA) (CCNPs-SF/HAMA) hydrogel for the osteosarcoma therapy and bone regeneration was developed by photocuring and ethanol treatment. The micro or nanofibers networks were observed in the CCNPs-SF/HAMA hydrogel. The FTIR results demonstrated that alcohol vapor treatment caused an increase in β-sheets of SF, resulting in the high compression stress and Young’s modulus of CCNPs-SF/HAMA hydrogel. According to the water uptake analysis, SF caused a slight decrease in water uptake of CCNPs-SF/HAMA hydrogel while CCNPs could enhance the water uptake of it. The swelling kinetic results showed that both the CCNPs and the SF increased the swelling ratio of CCNPs-SF/HAMA hydrogel. The accumulative release profile of CCNPs-SF/HAMA hydrogel showed that the release of Cur from CCNPs-SF/HAMA hydrogel was accelerated when pH value was decreased from 7.4 to 5.5. Besides, compared with CCNPs, the CCNPs-SF/HAMA hydrogel had a more sustainable drug release, which was beneficial for the long-term treatment of osteosarcoma. In vitro assay results indicated that CCNPs-SF/HAMA hydrogel with equivalent Cur concentration of 150 μg/mL possessed both the effect of anti-cancer and promoting the proliferation of osteoblasts. These results suggest that CCNPs-SF/HAMA hydrogel with superior physical properties and the bifunctional osteosarcoma therapy and bone repair may be an excellent candidate for local cancer therapy and bone regeneration.