Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit...Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.展开更多
Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism ...Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats.The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane,with histological score decreasing from 3.12±0.27 to 2.20±0.22 and anti-adhesion effectiveness increasing from 21.61%to 44.72%.Mechanistically,the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively;thus,the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited.Consequently,excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)is largely reduced.For biocompatibility evaluation,PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes.Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds,which further delays the fibrosis process.It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.展开更多
Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recogni...Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation.However,different clusters of macrophages have various functions and receive multiple regulation,which are both still unknown.In our current study,multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury.The transcriptomes of over 74000 human single cells were profiled.As results,we found that SPP1^(+)macrophages,RGCC^(+)endothelial cells,ACKR1^(+)endothelial cells and ADAM12^(+)fibroblasts participated in tendon adhesion formation.Interestingly,despite specific fibrotic clusters in tendon adhesion,FOLR2^(+)macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells.Furthermore,ACKR1 was verified to regulate FOLR2^(+)macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R^(tdTomato) mice to lethally irradiated Ackr1^(-/-)mice(Ackr1^(-/-)chimeras;deficient in ACKR1)and control mice(WT chimeras).Compared with WT chimeras,the decline of FOLR2^(+)macrophages was also observed,indicating that ACKR1 was specifically involved in FOLR2^(+)macrophages migration.Taken together,our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis,but also uncovered a novel antifibrotic cluster of macrophages and their origin.These results provide potential therapeutic targets against human tendon adhesion.展开更多
目的:构建基于Android平台的电子信息系统,探讨其在手术室仪器设备电子化动态管理中的应用价值。方法:采用Java开发语言、SQL Server 2008 R2数据库开发工具、浏览器与服务器(B/S)架构,设置Linux内核层、运行层、函数库、应用框架和应...目的:构建基于Android平台的电子信息系统,探讨其在手术室仪器设备电子化动态管理中的应用价值。方法:采用Java开发语言、SQL Server 2008 R2数据库开发工具、浏览器与服务器(B/S)架构,设置Linux内核层、运行层、函数库、应用框架和应用层构建基于Android平台的电子信息系统。选取2023年4-9月上海健康医学院附属崇明医院手术室在用的145件仪器设备,基于Android平台电子信息系统应用前采用人工手工登记,对比Android平台电子信息系统应用前后手术室仪器设备管理质量评分、运行质量和管理人员能力评分。结果:应用Android平台电子信息系统后仪器设备使用和归位速度、安全性能、维修速度和清洁质量评分分别为(39.01±1.38)分、(39.79±1.05)分、(38.85±1.22)分和(38.49±2.41)分,均明显高于应用前,其差异有统计学意义(t=3.313、19.407、26.957、8.010,P<0.05);应用Android平台电子信息系统后仪器设备开机率、成本效益增幅和社会效益增幅分别为(96.17±5.33)%、(7.93±1.15)%和(10.74±1.09)%,均高于应用前,仪器设备运转率为(9.21±1.35)%,低于应用前,其差异有统计学意义(t=9.386、59.769、47.946、27.078,P<0.05);应有Android平台电子信息系统后仪器设备管理人员的理论知识、操作能力和安全意识考核评分分别为(39.79±2.07)分、(39.11±2.18)分和(19.65±2.44)分,均明显高于应用前,其差异有统计学意义(t=9.261、7.645、7.253,P<0.05)。结论:基于Android平台的电子信息系统应用于手术室仪器设备管理,有助于实现仪器设备的电子化动态管理,提高仪器设备管理质量和管理水平。展开更多
Ultrasensitive nanomechanical instruments,e.g.atomic force microscopy(AFM),can be used to perform delicate biomechanical measurements and reveal the complex mechanical environment of biological processes.However,these...Ultrasensitive nanomechanical instruments,e.g.atomic force microscopy(AFM),can be used to perform delicate biomechanical measurements and reveal the complex mechanical environment of biological processes.However,these instruments are limited because of their size and complex feedback system.In this study,we demonstrate a miniature fiber optical nanomechanical probe(FONP)that can be used to detect the mechanical properties of single cells and in vivo tissue measurements.A FONP that can operate in air and in liquids was developed by programming a microcantilever probe on the end face of a single-mode fiber using femtosecond laser two-photon polymerization nanolithography.To realize stiffness matching of the FONP and sample,a strategy of customizing the microcantilever’s spring constant according to the sample was proposed based on structure-correlated mechanics.As a proof-of concept,three FONPs with spring constants varying from 0.421 N m^(−1)to 52.6 N m^(−1)by more than two orders of magnitude were prepared.The highest microforce sensitivity was 54.5 nmμN^(−1)and the detection limit was 2.1 nN.The Young’s modulus of heterogeneous soft materials,such as polydimethylsiloxane,muscle tissue of living mice,onion cells,and MCF-7 cells,were successfully measured,which validating the broad applicability of this method.Our strategy provides a universal protocol for directly programming fiber-optic AFMs.Moreover,this method has no special requirements for the size and shape of living biological samples,which is infeasible when using commercial AFMs.FONP has made substantial progress in realizing basic biological discoveries,which may create new biomedical applications that cannot be realized by current AFMs.展开更多
Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue,a process known as skeletal interoception,which is crucial for maintaining bone homeostasis.The hypothalamus...Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue,a process known as skeletal interoception,which is crucial for maintaining bone homeostasis.The hypothalamus,located in the central nervous system(CNS),plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system,neuropeptide release,and neuroendocrine mechanisms.These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts(OBs),the activation of osteoclasts(OCs),and the functional activities of bone cells.Sensory nerves extensively innervate skeletal tissues,facilitating the transmission of interoceptive signals to the CNS.This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions.The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.展开更多
PPeritendinous adhesion formation(PAF)can substantially limit the range of motion of digits.However,the origin of myofibroblasts in PAF tissues is still unclear.In this study,we found that the concentration of active ...PPeritendinous adhesion formation(PAF)can substantially limit the range of motion of digits.However,the origin of myofibroblasts in PAF tissues is still unclear.In this study,we found that the concentration of active TGF-β1 and the numbers of macrophages,mesenchymal stromal cells(MSCs),and myofibroblasts in human and mouse adhesion tissues were increased.Furthermore,knockout of TGF-β1 in macrophages or TGF-β1R2 in MSCs inhibited PAF by reducing MSC and myofibroblast infiltration and collagenⅠandⅢdeposition,respectively.Moreover,we found that MSCs differentiated into myofibroblasts to form adhesion tissues.Systemic injection of the TGF-β–neutralizing antibody 1D11 during the granulation formation stage of PAF significantly reduced the infiltration of MSCs and myofibroblasts and,subsequently,PAF.These results suggest that macrophage-derived TGF-β1 recruits MSCs to form myofibroblasts in peritendinous adhesions.An improved understanding of PAF mechanisms could help identify a potential therapeutic strategy.展开更多
In this study, 30 sediment samples were collected from the lower reaches of the Shichuanhe River in Xi’an, Shaanxi Province, China, to test the distribution of heavy metal elements in this area and for an analysis of...In this study, 30 sediment samples were collected from the lower reaches of the Shichuanhe River in Xi’an, Shaanxi Province, China, to test the distribution of heavy metal elements in this area and for an analysis of the pollution levels of this area, hope to provide guidance on agricultural production activities in this region. The results show that the heavy metal elements in this area are mainly concentrated at the Qinghe River and Shichuanhe River confluences. Furthermore, the element contents are higher than that of the background levels of the continental crust(UCC) and close to the background levels of the soil from Shaanxi Province;the two most enriched elements are Cd and As, with contents of 0.79 and 22.7 mg·kg-1, respectively, and their contents are 3.8 and 1.72 times higher than that of the background values. Herein, the heavy metal pollution assessment methods applied indicated that Cd and As are the two most abundant pollutant elements in the area’s soils. As has a peak geo-accumulation index value of 3, and the pollution level is high, while Cd exhibits high potential ecological risks due to its high toxicity(potential risk index of 143) and an active fraction of more than 64%.In addition, a principal component analysis and hierarchical cluster analysis study showed that there are two sources of the heavy metals in this area. The Zn, As, Ni, Cu, Pb,and Cr are mainly from natural sources, and the Cd likely comes from a discharge of untreated agricultural wastewater in the region. The Cd which poses a high potential risk and mainly results from human activities, needs to be further monitored.展开更多
To interpret the common symmetric peaks caused by the large-scale structure in the complex S(f)spectrum from the heterodyne Doppler reflectometry(DR)measurement in EAST,a 2D circular-shaped O-mode full-wave model base...To interpret the common symmetric peaks caused by the large-scale structure in the complex S(f)spectrum from the heterodyne Doppler reflectometry(DR)measurement in EAST,a 2D circular-shaped O-mode full-wave model based on the finite-difference time-domain method is built.The scattering characteristics and the influences on the DR signal from various scales are investigated.When the structure is located around the cutoff layer,a moving radial or poloidal large-scale structure k_(θ)k_(θ),match(k_(θ),match is the theoretic wavenumber of Bragg scattering)could both generate an oscillation phase term called‘phase modulation’,and symmetrical peaks in the complex S(f)spectrum.It was found that the image-rejection ratio A_(−1)/A_(+1)(A_(±1)represents the amplitudes of±1 order modulation peaks)could be a feasible indicator for experiment comparison.In the case when the structure is near the cutoff layer with the same arrangement as the experiment for the edge DR channel,the curve of A_(−1)/A_(+1)versus kθcan be divided into three regions,weak asymmetrical range with k_(θ)/k_(0)0.15(k_(0)is the vacuum wavenumber),harmonics range with 0.15k_(θ)/k_(0)0.4,and Bragg scattering range of 0.4k_(θ)/k_(0)0.7.In the case when the structure is located away from the cutoff layer,the final complex S(f)spectrum is the simple superimposing of modulation and Bragg scattering,and the modulation peaks have an amplitude response nearly proportional to the local density fluctuation,called the‘propagationroute effect’.Under the H-mode experiment arrangement for the core DR,a critical fluctuation amplitude Amp(n_(e,Mod.@route))/Amp(n_(e,Tur.@MSA)∼1.3–4.1(Amp(n_(e,Mod.@route))refers to the pedestal large-scale structure amplitude and Amp(ne,Tur.@MSA)refers to turbulence amplitude at the main scattering area)is needed for the structure in the pedestal to be observed by the core DR measurement.The simulations are well consistent with the experimental results.These effects need to be carefully considered during the DR signal analyses as the injecting beam passes through the plasma region with large-scale structures.展开更多
The Doppler reflectometer(DR),a powerful diagnostic for the plasma perpendicular velocity(u⊥)and turbulence measurement,has been widely used in various fusion devices.Many efforts have been put into extracting the Do...The Doppler reflectometer(DR),a powerful diagnostic for the plasma perpendicular velocity(u⊥)and turbulence measurement,has been widely used in various fusion devices.Many efforts have been put into extracting the Doppler shift from the DR signal.There are several commonly used methods for Doppler shift extraction,such as the phase derivative,the center of gravity,and symmetric fitting(SFIT).However,the strong zero-order reflection component around 0 kHz may interfere with the calculation of the Doppler shift.To avoid the influence of the zerofrequency peak,the asymmetric fitting(AFIT)method was designed to calculate the Doppler shift.Nevertheless,the AFIT method may lead to an unacceptable error when the Doppler shift is relatively small compared to the half width at half maximum(HWHM).Therefore,an improved method,which can remove the zero-frequency peak and fit the remaining Doppler peak with a Gaussian function,is devised to extract the Doppler shift.This method can still work reliably whether the HWHM is larger than the Doppler shift or not.展开更多
基金supported by the National Natural Science Foundation of China,No.82201460(to YH)Nanjing Medical University Science and Technology Development Fund,No.NMUB20210202(to YH).
文摘Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.
基金supported by the National Natural Science Foundation of China(No.82172408,81772314,and 81922045)the Original Exploration project(22ZR1480300)+5 种基金Outstanding Academic Leaders(Youth)project(21XD1422900)of Shanghai Science and Technology Innovation Action PlanPrinciple Investigator Innovation Team of Both Shanghai Sixth People’s Hospital and Shanghai Institute of Nutrition and Health,Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program(No.20191829)The Second Three-Year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals of Shanghai Shenkang(No.SHDC2020CR4032)Shanghai Excellent Academic Leader ProgramShanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration(No.20DZ2254100)China Postdoctoral Science Foundation(2023M742347).
文摘Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats.The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane,with histological score decreasing from 3.12±0.27 to 2.20±0.22 and anti-adhesion effectiveness increasing from 21.61%to 44.72%.Mechanistically,the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively;thus,the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited.Consequently,excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)is largely reduced.For biocompatibility evaluation,PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes.Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds,which further delays the fibrosis process.It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.
基金supported by the National Natural Science Foundation of China(No.82172408)Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program(No.20191829)+1 种基金The Second Three-Year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals of Shanghai Shenkang(No.SHDC2020CR4032)Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration(No.20DZ2254100).
文摘Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation.However,different clusters of macrophages have various functions and receive multiple regulation,which are both still unknown.In our current study,multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury.The transcriptomes of over 74000 human single cells were profiled.As results,we found that SPP1^(+)macrophages,RGCC^(+)endothelial cells,ACKR1^(+)endothelial cells and ADAM12^(+)fibroblasts participated in tendon adhesion formation.Interestingly,despite specific fibrotic clusters in tendon adhesion,FOLR2^(+)macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells.Furthermore,ACKR1 was verified to regulate FOLR2^(+)macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R^(tdTomato) mice to lethally irradiated Ackr1^(-/-)mice(Ackr1^(-/-)chimeras;deficient in ACKR1)and control mice(WT chimeras).Compared with WT chimeras,the decline of FOLR2^(+)macrophages was also observed,indicating that ACKR1 was specifically involved in FOLR2^(+)macrophages migration.Taken together,our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis,but also uncovered a novel antifibrotic cluster of macrophages and their origin.These results provide potential therapeutic targets against human tendon adhesion.
文摘目的:构建基于Android平台的电子信息系统,探讨其在手术室仪器设备电子化动态管理中的应用价值。方法:采用Java开发语言、SQL Server 2008 R2数据库开发工具、浏览器与服务器(B/S)架构,设置Linux内核层、运行层、函数库、应用框架和应用层构建基于Android平台的电子信息系统。选取2023年4-9月上海健康医学院附属崇明医院手术室在用的145件仪器设备,基于Android平台电子信息系统应用前采用人工手工登记,对比Android平台电子信息系统应用前后手术室仪器设备管理质量评分、运行质量和管理人员能力评分。结果:应用Android平台电子信息系统后仪器设备使用和归位速度、安全性能、维修速度和清洁质量评分分别为(39.01±1.38)分、(39.79±1.05)分、(38.85±1.22)分和(38.49±2.41)分,均明显高于应用前,其差异有统计学意义(t=3.313、19.407、26.957、8.010,P<0.05);应用Android平台电子信息系统后仪器设备开机率、成本效益增幅和社会效益增幅分别为(96.17±5.33)%、(7.93±1.15)%和(10.74±1.09)%,均高于应用前,仪器设备运转率为(9.21±1.35)%,低于应用前,其差异有统计学意义(t=9.386、59.769、47.946、27.078,P<0.05);应有Android平台电子信息系统后仪器设备管理人员的理论知识、操作能力和安全意识考核评分分别为(39.79±2.07)分、(39.11±2.18)分和(19.65±2.44)分,均明显高于应用前,其差异有统计学意义(t=9.261、7.645、7.253,P<0.05)。结论:基于Android平台的电子信息系统应用于手术室仪器设备管理,有助于实现仪器设备的电子化动态管理,提高仪器设备管理质量和管理水平。
基金supported by the National Natural Science Foundation of China(NSFC)(62122057,62075136,62175165)Natural Science Foundation of Guangdong Province(2022B1515120061,2019B1515120042)Science and Technology Innovation Commission of Shenzhen(RCYX20200714114524139,JCYJ20200109114001806).
文摘Ultrasensitive nanomechanical instruments,e.g.atomic force microscopy(AFM),can be used to perform delicate biomechanical measurements and reveal the complex mechanical environment of biological processes.However,these instruments are limited because of their size and complex feedback system.In this study,we demonstrate a miniature fiber optical nanomechanical probe(FONP)that can be used to detect the mechanical properties of single cells and in vivo tissue measurements.A FONP that can operate in air and in liquids was developed by programming a microcantilever probe on the end face of a single-mode fiber using femtosecond laser two-photon polymerization nanolithography.To realize stiffness matching of the FONP and sample,a strategy of customizing the microcantilever’s spring constant according to the sample was proposed based on structure-correlated mechanics.As a proof-of concept,three FONPs with spring constants varying from 0.421 N m^(−1)to 52.6 N m^(−1)by more than two orders of magnitude were prepared.The highest microforce sensitivity was 54.5 nmμN^(−1)and the detection limit was 2.1 nN.The Young’s modulus of heterogeneous soft materials,such as polydimethylsiloxane,muscle tissue of living mice,onion cells,and MCF-7 cells,were successfully measured,which validating the broad applicability of this method.Our strategy provides a universal protocol for directly programming fiber-optic AFMs.Moreover,this method has no special requirements for the size and shape of living biological samples,which is infeasible when using commercial AFMs.FONP has made substantial progress in realizing basic biological discoveries,which may create new biomedical applications that cannot be realized by current AFMs.
基金supported by the National Natural Science Foundation of China (No.82172408,81902234,81772314,and 81922045)the Original Exploration project (22ZR1480300)+4 种基金Outstanding Academic Leaders (Youth)project (21XD1422900)of Shanghai Science and Technology Innovation Action PlanPrinciple Investigator Innovation Team of Both Shanghai Sixth People’s Hospital and Shanghai Institute of Nutrition and Health,Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program (No.20191829)The Second Three-Year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals of Shanghai Shenkang (No.SHDC2020CR4032)Shanghai Excellent Academic Leader ProgramShanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration (No.20DZ2254100)。
文摘Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue,a process known as skeletal interoception,which is crucial for maintaining bone homeostasis.The hypothalamus,located in the central nervous system(CNS),plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system,neuropeptide release,and neuroendocrine mechanisms.These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts(OBs),the activation of osteoclasts(OCs),and the functional activities of bone cells.Sensory nerves extensively innervate skeletal tissues,facilitating the transmission of interoceptive signals to the CNS.This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions.The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.
基金supported in part by Fox and Necrosis funds from the Department of Orthopedic Surgery。
文摘PPeritendinous adhesion formation(PAF)can substantially limit the range of motion of digits.However,the origin of myofibroblasts in PAF tissues is still unclear.In this study,we found that the concentration of active TGF-β1 and the numbers of macrophages,mesenchymal stromal cells(MSCs),and myofibroblasts in human and mouse adhesion tissues were increased.Furthermore,knockout of TGF-β1 in macrophages or TGF-β1R2 in MSCs inhibited PAF by reducing MSC and myofibroblast infiltration and collagenⅠandⅢdeposition,respectively.Moreover,we found that MSCs differentiated into myofibroblasts to form adhesion tissues.Systemic injection of the TGF-β–neutralizing antibody 1D11 during the granulation formation stage of PAF significantly reduced the infiltration of MSCs and myofibroblasts and,subsequently,PAF.These results suggest that macrophage-derived TGF-β1 recruits MSCs to form myofibroblasts in peritendinous adhesions.An improved understanding of PAF mechanisms could help identify a potential therapeutic strategy.
基金financially supported by the Key Project of Shaanxi Provincial Natural Science Basic Research Program(2023-JC-ZD-16).
文摘In this study, 30 sediment samples were collected from the lower reaches of the Shichuanhe River in Xi’an, Shaanxi Province, China, to test the distribution of heavy metal elements in this area and for an analysis of the pollution levels of this area, hope to provide guidance on agricultural production activities in this region. The results show that the heavy metal elements in this area are mainly concentrated at the Qinghe River and Shichuanhe River confluences. Furthermore, the element contents are higher than that of the background levels of the continental crust(UCC) and close to the background levels of the soil from Shaanxi Province;the two most enriched elements are Cd and As, with contents of 0.79 and 22.7 mg·kg-1, respectively, and their contents are 3.8 and 1.72 times higher than that of the background values. Herein, the heavy metal pollution assessment methods applied indicated that Cd and As are the two most abundant pollutant elements in the area’s soils. As has a peak geo-accumulation index value of 3, and the pollution level is high, while Cd exhibits high potential ecological risks due to its high toxicity(potential risk index of 143) and an active fraction of more than 64%.In addition, a principal component analysis and hierarchical cluster analysis study showed that there are two sources of the heavy metals in this area. The Zn, As, Ni, Cu, Pb,and Cr are mainly from natural sources, and the Cd likely comes from a discharge of untreated agricultural wastewater in the region. The Cd which poses a high potential risk and mainly results from human activities, needs to be further monitored.
基金supported by Shenzhen Clean Energy Research Institute,the National MCF Energy R&D Program of China(Nos.2018YFE0311200 and 2022YFE03070004)National Natural Science Foundation of China(Nos.U1967206 and 12075155)+1 种基金the China Postdoctoral Science Foundation(No.2021M702270)the Fundamental Research Funds for the Central Universities(No.WK3420000018)。
文摘To interpret the common symmetric peaks caused by the large-scale structure in the complex S(f)spectrum from the heterodyne Doppler reflectometry(DR)measurement in EAST,a 2D circular-shaped O-mode full-wave model based on the finite-difference time-domain method is built.The scattering characteristics and the influences on the DR signal from various scales are investigated.When the structure is located around the cutoff layer,a moving radial or poloidal large-scale structure k_(θ)k_(θ),match(k_(θ),match is the theoretic wavenumber of Bragg scattering)could both generate an oscillation phase term called‘phase modulation’,and symmetrical peaks in the complex S(f)spectrum.It was found that the image-rejection ratio A_(−1)/A_(+1)(A_(±1)represents the amplitudes of±1 order modulation peaks)could be a feasible indicator for experiment comparison.In the case when the structure is near the cutoff layer with the same arrangement as the experiment for the edge DR channel,the curve of A_(−1)/A_(+1)versus kθcan be divided into three regions,weak asymmetrical range with k_(θ)/k_(0)0.15(k_(0)is the vacuum wavenumber),harmonics range with 0.15k_(θ)/k_(0)0.4,and Bragg scattering range of 0.4k_(θ)/k_(0)0.7.In the case when the structure is located away from the cutoff layer,the final complex S(f)spectrum is the simple superimposing of modulation and Bragg scattering,and the modulation peaks have an amplitude response nearly proportional to the local density fluctuation,called the‘propagationroute effect’.Under the H-mode experiment arrangement for the core DR,a critical fluctuation amplitude Amp(n_(e,Mod.@route))/Amp(n_(e,Tur.@MSA)∼1.3–4.1(Amp(n_(e,Mod.@route))refers to the pedestal large-scale structure amplitude and Amp(ne,Tur.@MSA)refers to turbulence amplitude at the main scattering area)is needed for the structure in the pedestal to be observed by the core DR measurement.The simulations are well consistent with the experimental results.These effects need to be carefully considered during the DR signal analyses as the injecting beam passes through the plasma region with large-scale structures.
基金supported in part by the National MCF Energy R&D Program(Nos.2018YFE0311200 and 2017YFE0301204)National Natural Science Foundation of China(Nos.U1967206,11975231 and 11922513)supported by the Users with Excellence Program of Hefei Science Center CAS(No.2020HSC-UE009).
文摘The Doppler reflectometer(DR),a powerful diagnostic for the plasma perpendicular velocity(u⊥)and turbulence measurement,has been widely used in various fusion devices.Many efforts have been put into extracting the Doppler shift from the DR signal.There are several commonly used methods for Doppler shift extraction,such as the phase derivative,the center of gravity,and symmetric fitting(SFIT).However,the strong zero-order reflection component around 0 kHz may interfere with the calculation of the Doppler shift.To avoid the influence of the zerofrequency peak,the asymmetric fitting(AFIT)method was designed to calculate the Doppler shift.Nevertheless,the AFIT method may lead to an unacceptable error when the Doppler shift is relatively small compared to the half width at half maximum(HWHM).Therefore,an improved method,which can remove the zero-frequency peak and fit the remaining Doppler peak with a Gaussian function,is devised to extract the Doppler shift.This method can still work reliably whether the HWHM is larger than the Doppler shift or not.