A Rigid Nanoplatform for Precise and Responsive Treatment of Intracellular Multidrug-Resistant Bacteria

Antibiotic treatment failure against life-threatening bacterial pathogens is typically caused by the rapid emergence and dissemination of antibiotic resistance.The current lack of antibiotic discovery and development urgently calls for new strategies to combat multidrug-resistant(MDR)bacteria,especially those that survive in host cells.Functional nanoparticles are promising intracellular drug delivery systems whose advantages include their high biocompatibility and tunable surface modifications.Inspired by the fact that the rigidity of nanoparticles potentiates their cellular uptake,rigidity-functionalized nanoparticles(RFNs)coated with bacteria-responsive phospholipids were fabricated to boost endocytosis,resulting in the increased accumulation of intracellular antibiotics.Precise delivery and high antibacterial efficacy were demonstrated by the clearing of 99%of MDR bacteria in 4 h using methicillin-resistant Staphylococcus aureus(MRSA)and pathogenic Bacillus cereus as models.In addition,the subcellular distribution of the RFNs was modulated by altering the phospholipid composition on the surface,thereby adjusting the electrostatic effects and reprograming the intracellular behavior of the RFNs by causing them to accurately target lysosomes.Finally,the RFNs showed high efficacy against MRSA-associated infections in animal models of wound healing and bacteremia.These findings provide a controllable rigidity-regulated delivery platform with responsive properties for precisely reprograming the accumulation of cytosolic antibiotics,shedding light on precision antimicrobial therapeutics against intracellular bacterial pathogens in the future.

Long-Term Preservation of Electronic Record Based on Digital Continuity in Smart Cities

Under the co-promotion of the wave of urbanization and the rise of data science,smart cities have become the new concept and new practice of urban development.Smart cities are the combination of information technology represented by the Internet of Things,cloud computing,mobile networks and big data,and urbanization.How to effectively achieve the long-term preservation of massive,heterogeneous,and multi-source digital electronic records in smart cities is a key issue thatmust be solved.Digital continuity can ensure the accessibility,integrity and availability of information.The quality management of electronic record,like the quality management of product,will run through every phase of the urban lifecycle.Based on data quality management,this paper constructs digital continuity of smart city electronic records.Furthermore,thework in this paper ensures the authenticity,integrity,availability and timeliness of electronic documents by quality management of electronic record.This paper elaborates on the overall technical architecture of electronic record,as well as the various technical means needed to protect its four characteristics.

Equisetin is an anti-obesity candidate through targeting 11β-HSD1

Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin(EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate.We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1’s substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess11β-HSD1 products, EQST’s anti-obesity effects disappeared. Furthermore, EQST directly bond to11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.