Utilization of the body’s regenerative potential for tissue repair is known as in situ tissue regeneration.However,the use of exogenous growth factors requires delicate control of the dose and delivery strategies and...Utilization of the body’s regenerative potential for tissue repair is known as in situ tissue regeneration.However,the use of exogenous growth factors requires delicate control of the dose and delivery strategies and may be accompanied by safety,efficacy and cost concerns.In this study,we developed,for the first time,a biomaterial-based strategy to activate endogenous transforming growth factor beta 1(TGFβ1)under alkaline conditions for effective in situ tissue regeneration.We demonstrated that alkaline-activated TGFβ1 from blood serum,bone marrow fluids and soaking solutions of meniscus and tooth dentin was capable of increasing cell recruitment and early differentiation,implying its broad practicability.Furthermore,we engineered an injectable hydrogel(MS-Gel)consisting of gelatin microspheres for loading strong alkaline substances and a modified gelatin matrix for hydrogel click crosslinking.In vitro models showed that alkaline MS-Gel controllably and sustainably activated endogenous TGFβ1 from tooth dentin for robust bone marrow stem cell migration.More importantly,infusion of in vivo porcine prepared root canals with alkaline MS-Gel promoted significant pulp-dentin regeneration with neurovascular stroma and mineralized tissue by endogenous proliferative cells.Therefore,this work offers a new bench-to-beside translation strategy using biomaterial-activated endogenous biomolecules to achieve in situ tissue regeneration without the need for cell or protein delivery.展开更多
A new search for two-neutrino double-beta(2νββ)decay of^(136)Xe to the 0+1 excited state of 136Ba is performed with the full EXO-200 dataset.A deep learning-based convolutional neural network is used to discriminat...A new search for two-neutrino double-beta(2νββ)decay of^(136)Xe to the 0+1 excited state of 136Ba is performed with the full EXO-200 dataset.A deep learning-based convolutional neural network is used to discriminate signal from background events.Signal detection efficiency is increased relative to previous searches by EXO-200 by more than a factor of two.With the addition of the Phase II dataset taken with an upgraded detector,the median 90%confidence level half-life sensitivity of 2νββdecay to the 0+1 state of 136Ba is 2.9×10^(24)yr using a total^(136)Xe exposure of 234.1 kg yr.No statistically significant evidence for 2νββdecay to the 0^(+)_(1)state is observed,leading to a lower limit of T2ν1/2(0^(+)→0^(+)_(1))>1.4×10^(24)yr at 90%confidence level,improved by 70%relative to the current world's best constraint.展开更多
文摘Utilization of the body’s regenerative potential for tissue repair is known as in situ tissue regeneration.However,the use of exogenous growth factors requires delicate control of the dose and delivery strategies and may be accompanied by safety,efficacy and cost concerns.In this study,we developed,for the first time,a biomaterial-based strategy to activate endogenous transforming growth factor beta 1(TGFβ1)under alkaline conditions for effective in situ tissue regeneration.We demonstrated that alkaline-activated TGFβ1 from blood serum,bone marrow fluids and soaking solutions of meniscus and tooth dentin was capable of increasing cell recruitment and early differentiation,implying its broad practicability.Furthermore,we engineered an injectable hydrogel(MS-Gel)consisting of gelatin microspheres for loading strong alkaline substances and a modified gelatin matrix for hydrogel click crosslinking.In vitro models showed that alkaline MS-Gel controllably and sustainably activated endogenous TGFβ1 from tooth dentin for robust bone marrow stem cell migration.More importantly,infusion of in vivo porcine prepared root canals with alkaline MS-Gel promoted significant pulp-dentin regeneration with neurovascular stroma and mineralized tissue by endogenous proliferative cells.Therefore,this work offers a new bench-to-beside translation strategy using biomaterial-activated endogenous biomolecules to achieve in situ tissue regeneration without the need for cell or protein delivery.
文摘A new search for two-neutrino double-beta(2νββ)decay of^(136)Xe to the 0+1 excited state of 136Ba is performed with the full EXO-200 dataset.A deep learning-based convolutional neural network is used to discriminate signal from background events.Signal detection efficiency is increased relative to previous searches by EXO-200 by more than a factor of two.With the addition of the Phase II dataset taken with an upgraded detector,the median 90%confidence level half-life sensitivity of 2νββdecay to the 0+1 state of 136Ba is 2.9×10^(24)yr using a total^(136)Xe exposure of 234.1 kg yr.No statistically significant evidence for 2νββdecay to the 0^(+)_(1)state is observed,leading to a lower limit of T2ν1/2(0^(+)→0^(+)_(1))>1.4×10^(24)yr at 90%confidence level,improved by 70%relative to the current world's best constraint.
