Differences in microbial community structure and metabolic activity among tea plantation soils under different management strategies.

Introduction: Microorganisms play an important role in the multifunctionality of soil ecosystems. Soil microbial diversity and functions have a great impact on plant growth and development. The interactions between tea trees and soil microbiota can be linked with planting patterns and management strategies, whose effects on soil microbial community structure and metabolites are still unclear. Methods: Here we used amplicon sequencing and metabolomic analysis to investigate the differences in soil microbial composition and metabolites among three tea production systems: organic, non-organic, and intercropping. Results: We detected significant differences among the three systems and found that Firmicutes, Proteobacteria, Acidobacteriota, Actinobacteriota and Chloroflexi were the main bacteria in the three soil groups, although they varied in relative abundance. Acidobacteria bacterium increased significantly in the organic and intercropping groups. For fungi, Ascomycota and Basidiomycota were the main differential fungal phyla. Fungi alpha-diversity in the non-organic group was significantly higher than that in the other two groups, and was correlated with multiple soil physical and chemical factors. Moreover, network analysis showed that bacteria and fungi were strongly correlated. The changes in soil microorganisms caused by management and planting patterns may affect soil quality through corresponding changes in metabolites. Metabolomic analysis showed differences in metabolite composition among different groups. It was also found that the arachidonic acid metabolic pathway was affected by changes in soil microorganisms, and may further affect soil quality in an essential manner. Discussion: Planting patterns and management strategies may significantly affect soil microorganisms and therefore metabolites. Changes in soil microorganisms, especially in fungi, may alter soil quality by affecting soil physicochemical properties and metabolites. This study will provide new insights into soil quality monitoring from a microbiological perspective.

Widely targeted metabolomics and HPLC analysis elaborated the quality formation of Yunnan pickled tea during the whole process at an industrial scale.

Yunnan pickled tea is produced from fresh tea-leaves through fixation, rolling, anaerobic fermentation and sun-drying. In this study, widely targeted metabolomics using UHPLC-QQQ-MS/MS and HPLC analysis were carried out to elaborate its quality formation during the whole process. Results confirmed the contribution of preliminary treatments and anaerobic fermentation to the quality formation. A total of 568 differential metabolites (VIP > 1.0, P < 0.05, FC > 1.50 or < 0.67) were screened through OPLS-DA. (-)-Epigallocatechin and (-)-epicatechin significantly (P < 0.05) increased from the hydrolyzation of ester catechins, such as (-)-epigallocatechin gallate and (-)-epicatechin gallate in anaerobic fermentation. Additionally, the anaerobic fermentation promoted vast accumulations of seven essential amino acids, four phenolic acids, three flavones and flavone glycosides, pelargonidin and pelargonidin glycosides, flavonoids and flavonoid glycosides (i.e. kaempferol, quercetin, taxifolin, apigenin, myricetin, luteolin and their glycosides) through relevant N-methylation, O-methylation, hydrolyzation, glycosylation and oxidation.

Study on Survival and Sustainable Development of Small- and Medium-Sized Tourism and Hospitality Enterprises in Macao Based on Regional Soft Environment and Competitive Advantage.

The small- and medium-sized tourism and hospitality enterprises are the main forms of enterprises in Macao. This study put forward a new framework of survival and sustainable development from the perspective of competitive advantage and regional soft environment, which significantly holds theoretical and practical research value. The study obtained cross-sectional data of 317 small- and medium-sized tourism and hospitality enterprises in Macao through a large-scale questionnaire survey. This article used exploratory factor analysis and confirmatory factor analysis to test the reliability and validity of each factor system and its measurement scale. The variance analysis is used to judge the differences between the elements. The regression analysis is used to verify the hypothesis of a causal relationship between factors. The structural equation analysis is used to fit the model and make necessary amendments. The results reveal that the government service environment has a significant positive impact on the ability of an entrepreneur. In addition, the regional soft environment significantly impacts the competitive advantage of small- and medium-sized tourism and hospitality enterprises in Macao. Contrary, the impact of laws of Macao on the acquisition of financial resources and the promotion of entrepreneur ability and innovation ability is found insignificant. In conclusion, the results showed that market of Macao lacks venture investors where enterprises cannot obtain funds through angel financing or risk financing.

Delivery of Doxorubicin from Hyaluronic Acid-Modified Glutathione-Responsive Ferrocene Micelles for Combination Cancer Therapy.

A combination of different chemotherapy approaches can obtain the best response for many cancers. However, the greatest challenge is the development of a nanoparticle formulation that can encapsulate different chemotherapeutic agents to achieve the proper synergetic chemotherapy for the tumor. Here, amphiphilic ferrocenium-tetradecyl (Fe-C14) was constructed to form cationic micelles in an aqueous solution via self-assembly. Then, it was coated by hyaluronic acid (HA) through electrostatic interactions to generate HA-Fe-C14 micelles. The HA-Fe-C14 micelles were used to deliver doxorubicin (DOX), and it showed that the DOX could be released rapidly under a high-GSH tumor environment. The HA-Fe-C14/DOX micelles were able to accumulate efficiently in tumor and showed significant anticancer effect both in vitro and in vivo. These results suggest that HA-Fe-C14/DOX micelles are a useful drug delivery system that enhances synergic antitumor treatment effects.

Hypoxia-responsive lipid-poly-(hypoxic radiosensitized polyprodrug) nanoparticles for glioma chemo- and radiotherapy.

Treatment of malignant glioma is a challenge facing cancer therapy. In addition to surgery, and chemotherapy, radiotherapy (RT) is one of the most effective modalities of glioma treatment. However, there are two crucial challenges for RT facing malignant glioma therapy: first, gliomas are known to be resistant to radiation due to their intratumoral hypoxia; second, radiosensitizers may exhibit a lack of target specificity, which may cause a lower concentration of radiosensitizers in tumors and toxic side effects in normal tissues. Thus, novel angiopep-2-lipid-poly-(metronidazoles)n (ALP-(MIs)n) hypoxic radiosensitizer-polyprodrug nanoparticles (NPs) were designed to enhance the radiosensitizing effect on gliomas. Methods: In this study, different degrees and biodegradabilites of hypoxic radiosensitizer MIs-based polyprodrug (P-(MIs)n) were synthesized as a hydrophobic core. P-(MIs)n were mixed with DSPE-PEG2000, angiopep-2-DSPE-PEG2000 and lecithin to self-assemble ALP-(MIs)n through a single-step nanoprecipitation method. The ALP-(MIs)n encapsulate doxorubicin (DOX) (ALP-(MIs)n/DOX) and provoke the release of DOX under hypoxic conditions for glioma chemo- and radiotherapy. In vivo glioma targeting was tested in an orthotopic glioma using live animal fluorescence/bioluminescence imaging. The effect on sensitization to RT of ALP-(MIs)n and the combination of chemotherapy and RT of ALP-(MIs)n/DOX for glioma treatment were also investigated both in vitro and in vivo. Results: ALP-(MIs)n/DOX effectively accumulated in gliomas and could reach the hypoxic glioma site after systemic in vivo administration. These ALP-(MIs)n showed a significant radiosensitizing effect on gliomas and realized combination chemotherapy and RT for glioma treatment both in vitro and in vivo. Conclusions: In summary, we constructed a lipid-poly-(hypoxic radiosensitized polyprodrug) nanoparticles for enhancing the RT sensitivity of gliomas and achieving the combination of radiation and chemotherapy for gliomas.

Design of Tumor Microenvironment-Responsive Drug-Drug Micelle for Cancer Radiochemotherapy.

Concomitant radiochemotherapy is a major therapeutic strategy for treating malignant tumors. However, the greatest challenge is how to improve the therapeutic effect of radiochemotherapy to achieve the proper synergetic chemo-/radiotherapy for the tumor. In this study, ferrocenium (antitumor effect) and nitroimidazole (hypoxic cell radiosensitization) conjugates were synthesized to form amphiphilic ferrocenium-hexane-nitroimidazole (Fe-NI), which can self-assemble in aqueous solution. The Fe-NI micelles successfully encapsulate the hydrophobic chemotherapy drug doxorubicin (DOX) and are modified with hyaluronic acid (HA) by electrostatic interactions to form HA-Fe-NIs-DOX micelles. HA-Fe-NIs-DOX micelles rapidly release DOX under tumor hypoxia and a high glutathione (GSH) environment and achieve a synergetic chemo-/radiotherapy for the tumor based on the properties of nitroimidazoles and ferrocenes. The biodistribution results obtained in vivo reveal an effective accumulation in the tumor. The HA-Fe-NIs-DOX micelles show a significant radiosensitizing effect on the tumors, and the combination of chemotherapy and radiotherapy is realized for the treatment of tumor in vitro and in vivo. These findings illustrate that HA-Fe-NIs micelles are a promising candidate, which enhances the antitumor effects as a DOX delivery system, owing to the synergistic mechanisms of antitumor agents and chemo-/radiotherapy.

Development of a hypoxia-triggered and hypoxic radiosensitized liposome as a doxorubicin carrier to promote synergetic chemo-/radio-therapy for glioma.

The treatment of malignant primary brain tumors is challenging. Concomitant radiochemotherapy has become the standard clinical treatment for malignant glioma, but there are two critical challenges to overcome in order to increase efficacy. First, glioma is known to have increased resistant to radiation due to its intra-tumoral hypoxia. In addition, the blood-brain barrier (BBB) restricts the distribution of the chemotherapeutic agent to the brain. Therefore, we developed a hypoxic radiosensitizer-prodrug liposome (MLP), in order to deliver DOX to the tumor and to overcome the above challenges, achieving a synergistic chemo-/radiotherapy treatment of malignant glioma. In this study, hypoxic radiosensitizer nitroimidazoles were conjugated with lipid molecules with a hydrolysable ester bond to form MDH. MDH was mixed together with DSPE-PEG2000 and cholesterol to make MLP liposomes, which were found to have strong radiosensitivity and to promote cargo release under hypoxic conditions, due to the properties of nitroimidazoles under hypoxic conditions. MLP/DOX was found to have distinct advantages, including precise and stealthy pharmacokinetics and efficient passive uptake by the tumor. Furthermore, the combination of MLP/DOX and radiotherapy (RT) significantly inhibited glioma growth as assessed by in vivo bioluminescence imaging. These findings suggest that MLP is a promising candidate as a DOX delivery system to enhance the antitumor treatment effects on glioma, owing to synergistic chemo-/radiotherapy.