Pulmonary delivery of mucus-traversing PF127-modified silk fibroin nanoparticles loading with quercetin for lung cancer therapy

The mucosal barrier remains a major barrier in the pulmonary drug delivery system,as mucociliary clearance in the airway accelerates the removal of inhaled nanoparticles(NPs).Herein,we designed and developed the inhalable Pluronic F127-modified silk fibroin NPs loading with quercetin(marked as QR-SF(PF127)NPs),aiming to solve the airway mucus barrier and improve the cancer therapeutic effect of QR.The PF127 coating on the SF NPs could attenuate the interaction between NPs and mucin proteins,thus facilitating the diffusion of SF(PF127)NPs in the mucus layer.The QR-SF(PF127)NPs had particle sizes of approximately 200 nm with negatively charged surfaces and showed constant drug release properties.Fluorescence recovery after photobleaching(FRAP)assay and transepithelial transport test showed that QR-SF(PF127)NPs exhibited superior mucus-penetrating ability in artificial mucus and monolayer Calu-3 cell model.Notably,a large amount of QR-SF(PF127)NPs distributed uniformly in the mice airway section,indicating the good retention of NPs in the respiratory tract.Themicemelanoma lungmetastasismodel was established,and the therapeutic effect of QR-SF(PF127)NPs was significantly improved in vivo.PF127-modified SF NPs may be a promising strategy to attenuate the interaction with mucin proteins and enhancemucus penetration efficiency in the pulmonary drug delivery system.

Gas-propelled nanomotors alleviate colitis through the regulation of intestinal immunoenvironment-hematopexis-microbiota circuits

The progression of ulcerative colitis(UC)is associated with immunologic derangement,intestinal hemorrhage,and microbiota imbalance.While traditional medications mainly focus on mitigating inflammation,it remains challenging to address multiple symptoms.Here,a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO_(2) nanospheres with Cu_(2)O nanoblocks.The resulting CaO_(2)–Cu_(2)O possessed a desirable diameter(291.3 nm)and a uniform size distribution.It could be efficiently internalized by colonic epithelial cells and macrophages,scavenge intracellular reactive oxygen/nitrogen species,and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 phenotype.This nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen bubbles.Rectal administration of CaO_(2)–Cu_(2)O could stanch the bleeding,repair the disrupted colonic epithelial layer,and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation,anti-oxidation,wound healing,and anti-inflammation.Impressively,it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria(e.g.,Odoribacter and Bifidobacterium)and decreasing the abundances of harmful bacteria(e.g.,Prevotellaceae and Helicobacter).Our gas-driven CaO_(2)–Cu_(2)O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation

Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer,their inefficient therapeutic outcomes,serious adverse effects,and high cost of mass production remain crucial challenges.Herein,we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers(TFENs).These nanovehicles had desirable particle sizes(131 nm),exosome-like morphology,and negative zeta potentials.Furthermore,TFENs were found to contain large amounts of polyphenols,flavonoids,functional proteins,and lipids.Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species(ROS)amplification.The increased intracellular ROS amounts could not only trigger mitochondrial damage,but also arrest cell cycle,resulting in the in vitro anti-proliferation,anti-migration,and anti-invasion activities against breast cancer cells.Further mice investigations demonstrated that TFENs after intravenous(i.v.)injection or oral administration could accumulate in breast tumors and lung metastatic sites,inhibit the growth and metastasis of breast cancer,and modulate gut microbiota.This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v.and oral routes.

Agro-climatic adaptation of cropping systems under climate change in Shanghai

Climate change affects the heat and water resources required by agriculture, thus shifting cropping rotation and intensity. Shanghai is located in the Taihu Lake basin, a transition zone for various cropping systems. In the basin, moderate climate changes can cause major shifts in cropping intensity and rotation. In the present study, we integrated observational climate data, one regional climate model, land use maps, and agricultural statistics to analyze the relationship between heat resources and multi-cropping potential in Shanghai. The results of agro-climatic assessment showed that climate change over the past 50 years has significantly enhanced regional agro- climatic resources, rendering a shift from double cropping to triple cropping possible. However, a downward trend is evident in the actual multi-cropping index, caused principally by the increasing costs of farming and limitations in the supply of labor. We argue that improving the utilization rate of the enhanced agro-climatic resources is possible by introducing new combinations of cultivars, adopting more laborsaving technologies, and providing incentives to farmers.

How silicon fertilizer improves nitrogen and phosphorus nutrient availability in paddy soil?

In order to reveal the mechanism of silicon(Si)fertilizer in improving nitrogen(N)and phosphorus(P)nutrient availability in paddy soil,we designed a series of soil culture experiments by combining application of varying Si fertilizer concentrations with fixed N and P fertilizer concentrations.Following the recommendations of fertilizer manufacturers and local farmers,we applied Si in concentrations of 0,5.2,10.4,15.6,and 20.8μg/kg.At each concentration of added Si,the availability of soil N and P nutrients,soil microbial activity,numbers of ammonia-oxidizing bacteria and P-decomposing bacteria which means that the organic P is decomposed into inorganic nutrients which can be absorbed and utilized by plants,and urease and phosphatase activity first increased,and then decreased,as Si was added to the soil.These indicators reached their highest levels with a Si application rate of 15.6μg/kg,showing values respectively 19.78%,105.09%,8.34%,73.12%,130.36%,28.12%,and 20.15%higher than those of the controls.Appropriate Si application(10.4 to 15.6µg/kg)could significantly increase the richness of the soil microbial community involved in cycling of N and P nutrients in the soil.When the Si application rate was 15.6μg/kg,parameters for characterizing microbial abundance such as sequence numbers,operational taxonomic unit(OTU)number,and correlation indices of microbial community richness such as Chao1 index,the adaptive coherence estimator(ACE)index,Shannon index,and Simpson index all reached maximum values,with amounts increased by 14.46%,10.01%,23.80%,30.54%,0.18%,and 2.64%,respectively,compared with the control group.There is also a good correlation between N and P mineralization and addition of Si fertilizer.The correlation coefficients between the ratio of available P/total P(AP/TP)and the number of ammonia-oxidizing bacteria,AP/TP and acid phosphatase activity(AcPA),AP/TP and the Shannon index,the ratio of available N/total amount of N(AN/TN)and the number of ammoniated bacteria,and AN/TN and AcPA were 0.9290,0.9508,0.9202,0.9140,and 0.9366,respectively.In summary,these results revealed that enhancement of soil microbial community structure diversity and soil microbial activity by appropriate application of Si is the key ecological mechanism by which application of Si fertilizer improves N and P nutrient availability.