Advanced fabric electronics for long-term personal physiological monitoring,with a self-sufficient energy source,high integrity,sensitivity,wearing comfort,and homogeneous components are urgently desired.Instead of as...Advanced fabric electronics for long-term personal physiological monitoring,with a self-sufficient energy source,high integrity,sensitivity,wearing comfort,and homogeneous components are urgently desired.Instead of assembling a self-powered biosensor,comprising a variety of materials with different levels of hardness,and supplementing with a booster or energy storage device,herein,an all-fiber integrated thermoelectrically powered physiological monitoring device(FPMD),is proposed and evaluated for production at an industrial scale.For the first time,an organic electrochemical transistor(OECT)biosensor is enabled by thermoelectric fabrics(TEFs)adaptively,sustainably and steadily without any additional accessories.Moreover,both the OECT and TEFs are constructed using a cotton/poly(3,4-ethylenedioxythiophene):poly(styrenesulfon ate)/dimethylsulfoxide/(3-glycidyloxypropyl)trimethoxysilane(PDG)yarn,which is lightweight,robust(90°bending for 1000 cycles)and sweat-resistant(ΔR/R0=1.9%).A small temperature gradient(ΔT=2.2 K)between the environment and the human body can drive the high-gain OECT(71.08 mS)with high fidelity,and a good signal to noise ratio.For practical applications,the on-body FPMD produced an enduring and steady output signal and demonstrated a linear monitoring region(sensitivity of 30.4 NCR(normalized current response)/dec,10 nM~50µM)for glucose in artificial sweat with reliable performance regarding anti-interference and reproducibility.This device can be expanded to the monitoring of various bio-markers and provides a new strategy for constructing wearable,comfortable,highly integrated and self-powered biosensors.展开更多
Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherap...Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N-Acetyl Pro–Gly–Pro(PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles(PGP-SLNs) to facilitate binding to neutrophils in vivo. Brain-targeted delivery to the basolateral amygdala(BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed in vitro and in vivo. The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized(OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell–nanoparticle delivery system for depression therapy.展开更多
Background and purpose Previous studies have reported about inflammation processes(IPs)that play important roles in aneurysm formation and rupture,which could be driven by blood flow.IPs can be identified using aneury...Background and purpose Previous studies have reported about inflammation processes(IPs)that play important roles in aneurysm formation and rupture,which could be driven by blood flow.IPs can be identified using aneurysmal wall enhancement(AWE)on high-resolution black-blood MRI(BB-MRI)and blood flow haemodynamics can be demonstrated by four-dimensional-flow MRI(4D-flow MRI).Thus,this study investigated the associations between AWE and haemodynamics in unruptured intracranial aneurysms(IA)by combining 4D-flow MRI and high-resolution BB-MRI.Materials and methods Between April 2014 and October 2017,48 patients with 49 unruptured IA who underwent both 4D-flow MRI and high-resolution BB-MRI were retrospectively included in this study.The haemodynamic parameters demonstrated using 4D-flow MRI were compared between different AWE patterns using the Kruskal-Wallis test and ordinal regression.Results The results of Kruskal-Wallis test showed that the average wall shear stress in the IA(WSSavg-IA),maximum through-plane velocity in the adjacent parent artery,inflow jet patterns and the average vorticity in IA(vorticityavg-IA)were significantly associated with the AWE patterns.Ordinal regression analysis identified WSSavg-IA(p=0.002)and vorticityavg-IA(p=0.033)as independent predictors of AWE patterns.Conclusion A low WSS and low average vorticity were independently associated with a high AWE grade for IAs larger than 4 mm.Therefore,WSS and average vorticity could predict AWE and circumferential AWE.展开更多
Two coumarins isolated from Aster praealtus were synthesized via a direct coupling of the corresponding cyclohexyl carbinol with a coumarin-derived aryl bromide or iodide, a very difficult etherification due to the ex...Two coumarins isolated from Aster praealtus were synthesized via a direct coupling of the corresponding cyclohexyl carbinol with a coumarin-derived aryl bromide or iodide, a very difficult etherification due to the excess steric congestion around the carbinol and the low reactivity of the aryl halide that frustrated many seemingly feasible protocols. Unequivocal ^1H and ^13C NMR data for these compounds were thus made available for the first time. Uncertainty and errors in ^1H and ^13C NMR data in previous reports are also eliminated and revealed, respectively.展开更多
A range of qinghaosu (artemisinin) analogues were synthesized from modified dihydroqinghao acid/aldehyde using dark singlet oxygen to trigger off the key step of the trioxane formation. The newly accessed 1,2,4-trio...A range of qinghaosu (artemisinin) analogues were synthesized from modified dihydroqinghao acid/aldehyde using dark singlet oxygen to trigger off the key step of the trioxane formation. The newly accessed 1,2,4-trioxanes featured a side chain extended from the carbon corresponding to the lactone carbonyl group of qinghaosu through a stable carbon-carbon single bond instead of an acetal oxygen-carbon bond in most similar analogues in the literature Biotin and various amines were also connected to the qinghaosu core, respectively, through such a linear tether in efforts to develop hybrids and potentially useful probes in search of the in vivo targets.展开更多
The asymmetric assembly and spontaneous resolution of chiral heterometal-organic frameworks from achiral precursors remain a great challenge. Herein, we report the formation and spontaneous resolution of three-dimensi...The asymmetric assembly and spontaneous resolution of chiral heterometal-organic frameworks from achiral precursors remain a great challenge. Herein, we report the formation and spontaneous resolution of three-dimensional(3 D) chiral 3 d-4 f heterometal-organic frameworks from achiral ligands in the presence of lactic acid enantiomers as chiral inducers. In the absence of a chiral inducer, the reactants randomly generated both enantiopure crystals in equal measure. However, enantiopure lactic acid induced asymmetric resolution to achieve single chiral crystallization. DFT theoretical calculations showed that the absolute chiral resolution of the enantiomers is due to the difference in the interactions between the two enantiomeric Λ/Δ-[Fe L_(3)]^(3-)units and the chiral inducer.展开更多
PRKCI,the gene for protein kinase Cι(PKCι),is frequently amplified in ovarian cancer and recent studies have shown that PKCιparticipates in ovary tumorigenesis.However,it is unknown whether PKCιis differentially i...PRKCI,the gene for protein kinase Cι(PKCι),is frequently amplified in ovarian cancer and recent studies have shown that PKCιparticipates in ovary tumorigenesis.However,it is unknown whether PKCιis differentially involved in the growth/survival between PRKCI-amplified and non-amplified ovarian cancer cells.In this study,we analyzed ovarian cancer patient dataset and revealed that PRKCI is the only PKC family member significantly amplified in ovarian cancer and PRKCI amplification is associated with higher PKCιexpression.Using a panel of ovarian cancer cell lines,we found that abundance of PKCιis generally associated with PRKCI amplification.Interestingly,silencing PKCιled to apoptosis in PRKCI-amplified ovarian cancer cells but not in those without PRKCI amplification,thus indicating an oncogenic addiction to PKCɩin PRKCI-amplified cells.Since small-molecule inhibitors characterized to selectively block atypical PKCs did not offer selectivity nor sensitivity in PRKCI-amplified ovarian cancer cells and were even cytotoxic to non-cancerous ovary surface or fallopian tube epithelial cells,we designed an EpCAM aptamer-PKCιsiRNA chimera(EpCAM-siPKCιaptamer).EpCAM-siPKCιaptamer not only effectively induced apoptosis of PRKCI-amplified ovarian cancer cells but also greatly deterred intraperitoneal tumor development in xenograft mouse model.This study has demonstrated a precision medicine-based strategy to target a subset of ovarian cancer that contains PRKCI amplification and shown that the EpCAM aptamerdelivered PKCιsiRNA may be used to suppress such tumors.展开更多
基金supported by the Natural Science Foundation of China(U20A20257)the National Key Research and Development Program(2022YFB3805803)+2 种基金Science and Technology Innovation Project of Hubei Province of China(2021BAA067)Outstanding Youth Project of Natural Science Foundation of Hubei Province of China(2021CFA068)Outstanding Young and Middleaged Innovation Team of Hubei Province of China(T2021007).
文摘Advanced fabric electronics for long-term personal physiological monitoring,with a self-sufficient energy source,high integrity,sensitivity,wearing comfort,and homogeneous components are urgently desired.Instead of assembling a self-powered biosensor,comprising a variety of materials with different levels of hardness,and supplementing with a booster or energy storage device,herein,an all-fiber integrated thermoelectrically powered physiological monitoring device(FPMD),is proposed and evaluated for production at an industrial scale.For the first time,an organic electrochemical transistor(OECT)biosensor is enabled by thermoelectric fabrics(TEFs)adaptively,sustainably and steadily without any additional accessories.Moreover,both the OECT and TEFs are constructed using a cotton/poly(3,4-ethylenedioxythiophene):poly(styrenesulfon ate)/dimethylsulfoxide/(3-glycidyloxypropyl)trimethoxysilane(PDG)yarn,which is lightweight,robust(90°bending for 1000 cycles)and sweat-resistant(ΔR/R0=1.9%).A small temperature gradient(ΔT=2.2 K)between the environment and the human body can drive the high-gain OECT(71.08 mS)with high fidelity,and a good signal to noise ratio.For practical applications,the on-body FPMD produced an enduring and steady output signal and demonstrated a linear monitoring region(sensitivity of 30.4 NCR(normalized current response)/dec,10 nM~50µM)for glucose in artificial sweat with reliable performance regarding anti-interference and reproducibility.This device can be expanded to the monitoring of various bio-markers and provides a new strategy for constructing wearable,comfortable,highly integrated and self-powered biosensors.
基金financial support from the National Natural Science Foundation of China (81673372, 81690263, 81361140344 and 81773911)the National Basic Research Program of China (2013CB 932502)+2 种基金the Opening Project of Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (Sichuan University, Chengdu, China)the Development Project of Shanghai Peak Disciplines–Integrated Medicine (No. 20150407)the Open Project Program of Key Lab of Smart Drug Delivery (Fudan University, Shanghai, China), Ministry of Education, China
文摘Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N-Acetyl Pro–Gly–Pro(PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles(PGP-SLNs) to facilitate binding to neutrophils in vivo. Brain-targeted delivery to the basolateral amygdala(BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed in vitro and in vivo. The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized(OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell–nanoparticle delivery system for depression therapy.
基金supported by the Natural Science Foundation of China(number 81971604)the Natural Science Foundation of China(number 81771233)+3 种基金the Natural Science Foundation of Beijing(number L192013)the Natural Science Foundation of China(number 81901197)Specific Research Projects for Capital Health Development(2018-2-2041)Beijing Science and Technology Planning Project:Beijing-Tianjin-Hebei Collaborative Innovation Promotion Project(Z181100009618035).
文摘Background and purpose Previous studies have reported about inflammation processes(IPs)that play important roles in aneurysm formation and rupture,which could be driven by blood flow.IPs can be identified using aneurysmal wall enhancement(AWE)on high-resolution black-blood MRI(BB-MRI)and blood flow haemodynamics can be demonstrated by four-dimensional-flow MRI(4D-flow MRI).Thus,this study investigated the associations between AWE and haemodynamics in unruptured intracranial aneurysms(IA)by combining 4D-flow MRI and high-resolution BB-MRI.Materials and methods Between April 2014 and October 2017,48 patients with 49 unruptured IA who underwent both 4D-flow MRI and high-resolution BB-MRI were retrospectively included in this study.The haemodynamic parameters demonstrated using 4D-flow MRI were compared between different AWE patterns using the Kruskal-Wallis test and ordinal regression.Results The results of Kruskal-Wallis test showed that the average wall shear stress in the IA(WSSavg-IA),maximum through-plane velocity in the adjacent parent artery,inflow jet patterns and the average vorticity in IA(vorticityavg-IA)were significantly associated with the AWE patterns.Ordinal regression analysis identified WSSavg-IA(p=0.002)and vorticityavg-IA(p=0.033)as independent predictors of AWE patterns.Conclusion A low WSS and low average vorticity were independently associated with a high AWE grade for IAs larger than 4 mm.Therefore,WSS and average vorticity could predict AWE and circumferential AWE.
基金This work was supported by the National Natural Science Foundation of China (Nos. 21172247, 21372248) and the Chinese Academy of Sciences.
文摘Two coumarins isolated from Aster praealtus were synthesized via a direct coupling of the corresponding cyclohexyl carbinol with a coumarin-derived aryl bromide or iodide, a very difficult etherification due to the excess steric congestion around the carbinol and the low reactivity of the aryl halide that frustrated many seemingly feasible protocols. Unequivocal ^1H and ^13C NMR data for these compounds were thus made available for the first time. Uncertainty and errors in ^1H and ^13C NMR data in previous reports are also eliminated and revealed, respectively.
基金This work was supported by the National Natural Science Foundation of China (21532002, 21672244, 21372248) and Chinese Academy of Sciences.
文摘A range of qinghaosu (artemisinin) analogues were synthesized from modified dihydroqinghao acid/aldehyde using dark singlet oxygen to trigger off the key step of the trioxane formation. The newly accessed 1,2,4-trioxanes featured a side chain extended from the carbon corresponding to the lactone carbonyl group of qinghaosu through a stable carbon-carbon single bond instead of an acetal oxygen-carbon bond in most similar analogues in the literature Biotin and various amines were also connected to the qinghaosu core, respectively, through such a linear tether in efforts to develop hybrids and potentially useful probes in search of the in vivo targets.
基金the National Natural Science Foundation of China (21871224, 21673184, 21721001)。
文摘The asymmetric assembly and spontaneous resolution of chiral heterometal-organic frameworks from achiral precursors remain a great challenge. Herein, we report the formation and spontaneous resolution of three-dimensional(3 D) chiral 3 d-4 f heterometal-organic frameworks from achiral ligands in the presence of lactic acid enantiomers as chiral inducers. In the absence of a chiral inducer, the reactants randomly generated both enantiopure crystals in equal measure. However, enantiopure lactic acid induced asymmetric resolution to achieve single chiral crystallization. DFT theoretical calculations showed that the absolute chiral resolution of the enantiomers is due to the difference in the interactions between the two enantiomeric Λ/Δ-[Fe L_(3)]^(3-)units and the chiral inducer.
文摘PRKCI,the gene for protein kinase Cι(PKCι),is frequently amplified in ovarian cancer and recent studies have shown that PKCιparticipates in ovary tumorigenesis.However,it is unknown whether PKCιis differentially involved in the growth/survival between PRKCI-amplified and non-amplified ovarian cancer cells.In this study,we analyzed ovarian cancer patient dataset and revealed that PRKCI is the only PKC family member significantly amplified in ovarian cancer and PRKCI amplification is associated with higher PKCιexpression.Using a panel of ovarian cancer cell lines,we found that abundance of PKCιis generally associated with PRKCI amplification.Interestingly,silencing PKCιled to apoptosis in PRKCI-amplified ovarian cancer cells but not in those without PRKCI amplification,thus indicating an oncogenic addiction to PKCɩin PRKCI-amplified cells.Since small-molecule inhibitors characterized to selectively block atypical PKCs did not offer selectivity nor sensitivity in PRKCI-amplified ovarian cancer cells and were even cytotoxic to non-cancerous ovary surface or fallopian tube epithelial cells,we designed an EpCAM aptamer-PKCιsiRNA chimera(EpCAM-siPKCιaptamer).EpCAM-siPKCιaptamer not only effectively induced apoptosis of PRKCI-amplified ovarian cancer cells but also greatly deterred intraperitoneal tumor development in xenograft mouse model.This study has demonstrated a precision medicine-based strategy to target a subset of ovarian cancer that contains PRKCI amplification and shown that the EpCAM aptamerdelivered PKCιsiRNA may be used to suppress such tumors.