Low-Energy Driven Ring-Opening Behavior of Benzocyclobutene Derivatives

It's urgent to develop benzocyclobutene(BCB)-based polymers with low curing temperature for temperature-sensitive applications such as liquid crystal displays(LCDs)and flexible electronics.Herein,the effect of substituents on the ring-opening behavior of BCB derivatives was investigated.The ring-opening activation energy barriers(ΔGA)of BCB derivatives with one or two substituents on the four-membered alkyl ring were systematically calculated using the B3LYP function.Both mono-and di-substituted BCBs adopted the conrotatory ring-opening process,obeying the Woodward-Hoffmann's Rules upon heating.The mono-/di-substituted BCBs exhibited 8.2%—69%lowerΔGA compared with BCB,attributed to the electronic effects of the substituents.Disubstituted BCBs with both electron-donating and electron-withdrawing groups,e.g.,1-NH_(2)-8-NO_(2)-BCB,demonstrated the lowestΔGA.In addition,BCB derivatives with amide/ester/acyloxy group modified on C1 position were synthesized as model molecules,and their ring-opening temperature can be decreased by 20℃ compared to the unsubstituted one,also consistent with our calculation results.This work combined theoretical calculation methods with experimental results to provide valuable insights into the design and synthesis of BCB derivatives and next-generation BCB functional packaging materials with low ring-opening temperature.

Targeted delivery of a STING agonist to brain tumors using bioengineered protein nanoparticles for enhanced immunotherapy

Immunotherapy is emerging as a powerful tool for combating many human diseases.However,the application of this life-saving treatment in serious brain diseases,including glioma,is greatly restricted.The major obstacle is the lack of effective technologies for transporting therapeutic agents across the blood-brain barrier(BBB)and achieving targeted delivery to specific cells once across the BBB.Ferritin,an iron storage protein,traverses the BBB via receptor-mediated transcytosis by binding to transferrin receptor 1(TfR1)overexpressed on BBB endothelial cells.Here,we developed bioengineered ferritin nanoparticles as drug delivery carriers that enable the targeted delivery of a small-molecule immunomodulator to achieve enhanced immunotherapeutic efficacy in an orthotopic glioma-bearing mouse model.We fused different glioma-targeting moieties on self-assembled ferritin nanoparticles via genetic engineering,and RGE fusion protein nanoparticles(RGE-HFn NPs)were identified as the best candidate.Furthermore,RGE-HFn NPs encapsulating a stimulator of interferon genes(STING)agonist(SR717@RGE-HFn NPs)maintained stable self-assembled structure and targeting properties even after traversing the BBB.In the glioma-bearing mouse model,SR717@RGE-HFn NPs elicited a potent local innate immune response in the tumor microenvironment,resulting in significant tumor growth inhibition and prolonged survival.Overall,this biomimetic brain delivery platform offers new opportunities to overcome the BBB and provides a promising approach for brain drug delivery and immunotherapy in patients with glioma.

Protein expression changes in cornea after collagen crosslinking

Riboflavin/UV-mediated corneal collagen cross-linking can increase the mechanical strength of the cornea and prevent or delay corneal expansion and keratoconus progression.We performed quantitative analysis of protein iTRAQ in rabbit eye white matter after cross-linking to explore the changes of protein expression in cornea at different times after cross-linking and to understand the process of corneal stroma remodeling after cross-linking.The screening conditions are fold Change
1.2 and P-value<0.05,we identified 713 and 38 differentially expressed proteins in cornea at 1 week and 1 month after cross-linking.There were 16 differentially expressed proteins at two time points after corneal cross-linking.By annotating the functions of these proteins,we identified some proteins that affect the mechanical properties of the cornea,and these proteins are involved in cell growth,oxidative stress response,and signal transduction in the cornea.It has a guiding role in studying the corneal stroma remodeling process after collagen crosslinking.