AIM:To determine whether paeonol(Pae),a naturally occurring phenolic compound,can serve as an effective pharmacological inhibitor of posterior capsular opacification(PCO).METHODS:A rat model of cataract surgery—induc...AIM:To determine whether paeonol(Pae),a naturally occurring phenolic compound,can serve as an effective pharmacological inhibitor of posterior capsular opacification(PCO).METHODS:A rat model of cataract surgery—induced PCO was established,and Pae was administered via anterior chamber injection to evaluate its preventive effect on capsular opacification and fibrotic remodeling.Histological and immunohistochemical analyses were performed to assess epithelial-mesenchymal transition(EMT)—related changes in lens epithelial cells(LECs).Ex vivo lens capsule cultures were employed to examine the expression of Vimentin and Zonula Occludens-1(ZO-1)by immunofluorescence and immunohistochemistry.In the human LEC line SRA01/04,EMT marker expression at both mRNA and protein levels was analyzed following transforming growth factor beta 2(TGF-β2)stimulation,with Pae treatment.Western blotting and immunofluorescence were used to investigate the effect of Pae on TGF-β/Smad signaling and AMP-activated protein kinase(AMPK)activation.Molecular docking was performed to predict Pae–AMPK binding,and rescue experiments with AMPK inhibition were conducted to validate the mechanistic pathway.RESULTS:Pae significantly reduced capsular opacification and fibrotic remodeling in the rat PCO model compared with controls.In LECs,Pae markedly suppressed TGF-β2–induced EMT,evidenced by decreased expression of mesenchymal markers,such as Vimentin,Fibronectin,Collagen 1A1,α-SMA and preserved epithelial junctional protein ZO-1.Mechanistically,Pae was predicted to directly interact with the catalytic pocket of AMPK,which was experimentally confirmed by enhanced AMPK phosphorylation and nuclear translocation(P<0.05).This activation disrupted canonical TGF-β/Smad signaling,leading to suppression of EMT.Rescue experiments using AMPK inhibition abrogated the anti-EMT effect of Pae,further validating the AMPK-dependent mechanism.CONCLUSION:Pae exerts a potent inhibitory effect on PCO formation by blocking EMT of LECs through direct activation of AMPK and subsequent disruption of TGF-β/Smad signaling.展开更多
Twisted multilayers of two-dimensional materials attract widespread research interest due to their intriguing electronic and optical properties related to their chiral symmetry breaking and moiréeffects.The two-d...Twisted multilayers of two-dimensional materials attract widespread research interest due to their intriguing electronic and optical properties related to their chiral symmetry breaking and moiréeffects.The two-dimensional transition metal dichalcogenide MoSe_(2) is a particularly promising material for twisted multilayers,capable of sustaining moiréexcitons.Here,we report on a rational bottomup synthesis approach for twisted MoSe_(2) flakes by chemical vapor transport(CVT).Screw dislocation-driven growth was forced by surface-fused SiO_(2)nanoparticles on the substrates that serve as potential nucleation points in low supersaturation condition.Thus,crystal growth by in-situ CVT under addition of MoCl_(5) leads to bulk 2H-MoSe_(2) in a temperature gradient from 900 to 820℃ with a dwell time of 96 h.Hexagonally shaped 2H-MoSe_(2) flakes were grown from 710 to 685℃ with a dwell time of 30 min on SiO_(2)@Al_(2)O_(3)(0001)substrates.Electron backscatter diffraction as well as electron microscopy reveals the screw dislocation-driven growth of triangular 3R-MoSe_(2) with individual step heights between 0.9 and 2.9 nm on SiO_(2)@Si(100)under the same conditions.Finally,twisted MoSe_(2) flakes exhibiting a twist angle of 19°with respect to the[010]zone axis could be synthesized.展开更多
基金Supported by the Projects of Medical and Health Technology Development Program in Shandong Province(No.202107021009)Shandong Provincial Traditional Chinese Medicine Science and Technology Project(No.M-2023118).
文摘AIM:To determine whether paeonol(Pae),a naturally occurring phenolic compound,can serve as an effective pharmacological inhibitor of posterior capsular opacification(PCO).METHODS:A rat model of cataract surgery—induced PCO was established,and Pae was administered via anterior chamber injection to evaluate its preventive effect on capsular opacification and fibrotic remodeling.Histological and immunohistochemical analyses were performed to assess epithelial-mesenchymal transition(EMT)—related changes in lens epithelial cells(LECs).Ex vivo lens capsule cultures were employed to examine the expression of Vimentin and Zonula Occludens-1(ZO-1)by immunofluorescence and immunohistochemistry.In the human LEC line SRA01/04,EMT marker expression at both mRNA and protein levels was analyzed following transforming growth factor beta 2(TGF-β2)stimulation,with Pae treatment.Western blotting and immunofluorescence were used to investigate the effect of Pae on TGF-β/Smad signaling and AMP-activated protein kinase(AMPK)activation.Molecular docking was performed to predict Pae–AMPK binding,and rescue experiments with AMPK inhibition were conducted to validate the mechanistic pathway.RESULTS:Pae significantly reduced capsular opacification and fibrotic remodeling in the rat PCO model compared with controls.In LECs,Pae markedly suppressed TGF-β2–induced EMT,evidenced by decreased expression of mesenchymal markers,such as Vimentin,Fibronectin,Collagen 1A1,α-SMA and preserved epithelial junctional protein ZO-1.Mechanistically,Pae was predicted to directly interact with the catalytic pocket of AMPK,which was experimentally confirmed by enhanced AMPK phosphorylation and nuclear translocation(P<0.05).This activation disrupted canonical TGF-β/Smad signaling,leading to suppression of EMT.Rescue experiments using AMPK inhibition abrogated the anti-EMT effect of Pae,further validating the AMPK-dependent mechanism.CONCLUSION:Pae exerts a potent inhibitory effect on PCO formation by blocking EMT of LECs through direct activation of AMPK and subsequent disruption of TGF-β/Smad signaling.
基金funding from SFB 1415 subproject B04(Deutsche Forschungsgemeinschaft,No.417590517)supported by the Deutsche Forschungsgemeinschaft through the Würzburg-Dresden Cluster of Excellence on Complexity and Topology in Quantum Matter-ct.qmat(EXC 2147,No.390858490)the support provided by the DRESDEN-concept alliance of research institutions.
文摘Twisted multilayers of two-dimensional materials attract widespread research interest due to their intriguing electronic and optical properties related to their chiral symmetry breaking and moiréeffects.The two-dimensional transition metal dichalcogenide MoSe_(2) is a particularly promising material for twisted multilayers,capable of sustaining moiréexcitons.Here,we report on a rational bottomup synthesis approach for twisted MoSe_(2) flakes by chemical vapor transport(CVT).Screw dislocation-driven growth was forced by surface-fused SiO_(2)nanoparticles on the substrates that serve as potential nucleation points in low supersaturation condition.Thus,crystal growth by in-situ CVT under addition of MoCl_(5) leads to bulk 2H-MoSe_(2) in a temperature gradient from 900 to 820℃ with a dwell time of 96 h.Hexagonally shaped 2H-MoSe_(2) flakes were grown from 710 to 685℃ with a dwell time of 30 min on SiO_(2)@Al_(2)O_(3)(0001)substrates.Electron backscatter diffraction as well as electron microscopy reveals the screw dislocation-driven growth of triangular 3R-MoSe_(2) with individual step heights between 0.9 and 2.9 nm on SiO_(2)@Si(100)under the same conditions.Finally,twisted MoSe_(2) flakes exhibiting a twist angle of 19°with respect to the[010]zone axis could be synthesized.
