Search

Protein kinases constitute a rich pool of biomarkers and therapeutic targets of tremendous diseases including cancer. However, sensing kinase activity in vivo while implementing treatments according to kinase hyperactivation remains challenging. Herein, we present a nanomediator-effector cascade system that can in situ magnify the subtle events of kinase-catalyzed phosphorylation via DNA amplification machinery to achieve kinase activity imaging and kinase-responsive drug release in vivo. In this cascade, the phosphorylation-mediated disassembly of DNA/peptide complex on the nanomediators initiated the detachment of fluorescent hairpin DNAs from the nanoeffectors via hybridization chain reaction (HCR), leading to fluorescence recovery and therapeutic cargo release. We demonstrated that this nanosystem simultaneously enabled trace protein kinase A (PKA) activity imaging and on-demand drug delivery for inhibition of tumor cell growth both in vitro and in vivo, affording a kinase-specific sense-and-treat paradigm for cancer theranostics.

Dynamically monitoring intracellular glutathione (GSH), a crucial biomarker of oxidative stress, is of significance for the diagnosis and treatment of certain diseases. Although manganese dioxide (MnO2) based GSH fluorescent sensors have exhibited high sensitivity and good selectivity owing to the specific reactivity between GSH and MnO2, near-infrared (NIR) MnO2 based nanoprobes for GSH detection are scarce. Herein, we have developed a NIR activatable fluorescence nanoprobe for the imaging and determination of intracellular GSH based on a core-shell nanoparticle, consisting of NIR emitted gold nanocluster doped silica as the fluorescent core and manganese dioxide as the GSH-responsive shell (named AuNCs@MnO2). Due to the absorption competition mechanism, the outer MnO2 shell rather than the inner AuNCs core preferentially absorbed the excitation light, thus leading to fluorescence quenching of the inner AuNCs core. Upon addition of GSH, the fluorescence of the nanoprobe restored along with the reduction of MnO2 to Mn2+ because of the absorption competition disappearance-induced emission. The activatable fluorescence linearly increased upon changing the GSH concentration in the range of 2 to 5000 μM with a detection limit of 0.67 μM. The cytotoxicity test shows that the AuNCs@MnO2 nanoprobes have a good biocompatibility. After entering the cancer cells, the intracellular GSH degraded the outermost MnO2 shell and initiated the NIR fluorescence restoration of AuNCs, which can be used to monitor the dynamic change of intracellular GSH. This strategy provides an NIR-activatable way to detect GSH levels in living cells and offers a promising platform for the diagnosis and treatment of GSH-related diseases.

River systems acts as the critical factor for site selection. In the process of rural evolution, river adaptability created by human settlement is fading away due to inadequate understanding of inherent spatial characteristics. To better understand the inherent law of the applicability of traditional villages river systems , this study proposed the concept of inheritance based on spatial measurement of the correlation between traditional villages and river systems. With the help of GIS10.8 and SPSS26.0 software, this study takes 658 national traditional villages of Hunan and domestic river systems as an example to measure the spatial correlation characteristics,which concludes spatial pattern, spatial density and spatial distance. Summarize the similarity and differences characteristics of spatial distribution. Analyse and interpret the impact index of spatial correlation through the stepwise regression model. The results actually showed that traditional villages are uneven distributed along river systems, which are mainly affected by minority population, elevation and farming industry. In addition, traditional villages are less with the increase of spatial distance from river systems. The values of spatial quantitative measurement and mechanism can reflect the traditional survival wisdom.It can guide significance for spatial growth mechanism of integration with environment and provide references for future conservation and utilization of spatial heritage sustainability.

Dynamically monitoring intracellular glutathione (GSH), a crucial biomarker of oxidative stress, is of significance for the diagnosis and treatment of certain diseases. Although manganese dioxide (MnO2) based GSH fluorescent sensors have exhibited high sensitivity and good selectivity owing to the specific reactivity between GSH and MnO2, near-infrared (NIR) MnO2 based nanoprobes for GSH detection are scarce. Herein, we have developed a NIR activatable fluorescence nanoprobe for the imaging and determination of intracellular GSH based on a core-shell nanoparticle, consisting of NIR emitted gold nanocluster doped silica as the fluorescent core and manganese dioxide as the GSH-responsive shell (named AuNCs@MnO2). Due to the absorption competition mechanism, the outer MnO2 shell rather than the inner AuNCs core preferentially absorbed the excitation light, thus leading to fluorescence quenching of the inner AuNCs core. Upon addition of GSH, the fluorescence of the nanoprobe restored along with the reduction of MnO2 to Mn2+ because of the absorption competition disappearance-induced emission. The activatable fluorescence linearly increased upon changing the GSH concentration in the range of 2 to 5000 μM with a detection limit of 0.67 μM. The cytotoxicity test shows that the AuNCs@MnO2 nanoprobes have a good biocompatibility. After entering the cancer cells, the intracellular GSH degraded the outermost MnO2 shell and initiated the NIR fluorescence restoration of AuNCs, which can be used to monitor the dynamic change of intracellular GSH. This strategy provides an NIR-activatable way to detect GSH levels in living cells and offers a promising platform for the diagnosis and treatment of GSH-related diseases.

In order to grasp the impact of climate change on tea and better develop tea meteorological services, according to the daily meteorological observation data of the National Meteorological Station of Guzhang County from 1981 to 2015 and the quality inspection data of the Tea Research Institute, fuzzy mathematics method and weighted index are used to study the occurrence and development of tea and its impact on Guzhang Maojian tea. The results showed that the annual average temperature increased obviously, the average date of daily mean temperature passing through 10 °was March 24, and the climate tendency rate was -3.8d/10a, and the changes of precipitation and sunshine hours tended to be consistent with those of tea growing season. The main meteorological disasters affecting the production of Guzhang Maojian tea are high temperature heat damage, frost, in which the high temperature heat damage is mainly mild to moderate, most of which occurs in July to August, and the frequency increases after 2000, which has an effect on summer and autumn tea, the number of frost days shows a decreasing trend, and the tendency rate is 1.123 d/10a, which is beneficial to the growth of tea. Climate change had no effect on tea quality. Dryness was less than 0.5, relative humidity was more than 80%, spring tea quality was high, total tea polyphenols, amino acids, caffeine and catechin were 22.41 ~28.85%, 3.79 ~ 7.96, 3.66 ~ 4.63% and 13.28 ~ 19.71, respectively. The quality of autumn tea comes next, and that of summer tea comes next. The research results can provide scientific basis for optimizing tea production layout and adapting to climate change.

Due to the growing number of emergency accidents occurring around students, evacuation issues have become significantly important for both school officials and architects. Simply following construction codes cannot ensure that a building׳s layout is suitable for evacuation behaviors; therefore, to discover the suitable planning schemes, we have introduced an agent-based simulation model via Netlogo to investigate the interrelationships between evacuation efficiency and classroom layouts. Before conducting modeling experiments, both the simulation structure and the sensitivity to its parameter settings are examined by validation research and sensitivity analysis. Furthermore, to demonstrate the importance of conducting fire drills with students, two different types of behavior rules are designed to reflect the distinctive characteristics of students evacuating without instructions and students evacuating in good order. The general comparison results show us that the classroom layout with two exits shortens students׳ evacuation time, and the premeditated behavior rules, meaning that students who follow preset instructions to arrange their activities, not only escape faster but also have some advantages in ensuring their safety during the evacuation process. Moreover, at the end of this paper, several methods of improving this simulation model are proposed for more complex research in the future.

In view of the poor accuracy of single value of heat energy consumption and the weak real-time monitoring of energy consumption in buildings, an intelligent monitoring system for thermal energy consumption of buildings under the internet of things (IoT) technology is designed. The overall structure of the intelligent monitoring system for thermal energy consumption of buildings is constructed. The DSP integrated signal processor is used for data acquisition and real-time information processing of thermal energy of buildings. A wireless intelligent gateway for building thermal energy consumption monitoring is designed by using internet of things technology, a wireless sensor network model is constructed. The VME bus is used as information transmission channel to realise intelligent monitoring for thermal energy consumption. The test results show that the real-time monitoring accuracy of the system is better than that of the traditional method and it has a good application prospect in all aspects.

Calculate the joint connection spring rigidity of prefabricated low multi-story villa according to relevant specification and take modeling analysis by using SAP2000 finite element analysis software. Respectively analyze elastic-plastic time-history under moderate earthquakes and major earthquakes, take checking calculation of structural safety and obtain the conclusion and support the project to complete smoothly so as to provide design basis for this kind of multi-story prefabricatedvilla.