To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and...To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of liposomes.The results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their liposomes.The pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in vivo.The C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 cells.According to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting capabilities.The results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.展开更多
Steel structures are widely used in railway infrastructures.Their stress state is the most important determinant of the safety of these structures.The elasto-magnetic (EM) sensor is the most promising for stress monit...Steel structures are widely used in railway infrastructures.Their stress state is the most important determinant of the safety of these structures.The elasto-magnetic (EM) sensor is the most promising for stress monitoring of in-service steel structures.Nevertheless,the necessity of magnetic excitation to saturation due to the use of a secondary coil for signal detection,keeps from its engineering application.In this paper,a smart elasto-magneto-electric (EME) sensor using magneto-electric (ME) sensing units to take the place of the secondary coil has been exploited for the first time.The ME sensing unit is made of ME laminated composites,which has an ultrahigh ME voltage coefficient and can measure the magnetic induction simply and precisely.Theoretical analysis and characterization experiments firstly conducted on the ME laminated composites showed that the ME sensing units can be applied in the EM sensor for improved performance in stress monitoring.A tension test of a steel bar was carried out to characterize our smart EME sensor and the results showed high accuracy and sensitivity.The present smart EME sensor is a promising tool for stress monitoring of steel structures in railway and other civil infrastructures.展开更多
An in vitro blood-brain barrier(BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous system.Though many models have been developed, their reproducib...An in vitro blood-brain barrier(BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous system.Though many models have been developed, their reproducibility and renewability remain a challenge. Furthermore, drug transport data from many of the models do not correlate well with the data for in vivo BBB drug transport.Induced-pluripotent stem cell(i PSC) technology provides reproducible cell resources for in vitro BBB modeling.Here, we generated a human in vitro BBB model by differentiating the human i PSC(hi PSC) line GM25256 into brain endothelial-type cells. The model displayed BBB characteristics including tight junction proteins(ZO-1,claudin-5, and occludin) and endothelial markers(von Willebrand factor and Ulex), as well as high transendothelial electrical resistance(TEER)(1560 X.cm2±230 X.cm2) and c-GTPase activity. Co-culture with primary rat astrocytes significantly increased the TEER of the model(2970 X.cm2 to 4185 X.cm2). RNAseq analysis confirmed the expression of key BBB-related genes in the hi PSC-derived endothelial cells in comparison with primary human brain microvascular endothelial cells,including P-glycoprotein(Pgp) and breast cancer resistant protein(BCRP). Drug transport assays for nine CNS compounds showed that the permeability of non-Pgp/BCRP and Pgp/BCRP substrates across the model was strongly correlated with rodent in situ brain perfusion data for these compounds(R2= 0.982 and R2= 0.9973,respectively), demonstrating the functionality of the drug transporters in the model. Thus, this model may be used to rapidly screen CNS compounds, to predict the in vivo BBB permeability of these compounds and to study the biology of the BBB.展开更多
The complex mechanical and damage mechanisms of rocks are intricately tied to their diverse mineral compositions and the formation of pores and cracks under external loads.Numerous rock tests reveal a complex interpla...The complex mechanical and damage mechanisms of rocks are intricately tied to their diverse mineral compositions and the formation of pores and cracks under external loads.Numerous rock tests reveal a complex interplay between the closure of porous defects and the propagation of induced cracks,presenting challenges in accurately representing their mechanical properties,especially under true triaxial stress conditions.This paper proposes a conceptualization of rock at the mesoscopic level as a two-phase composite,consisting of a bonded medium matrix and frictional medium inclusions.The bonded medium is characterized as a mesoscopic elastic material,encompassing various minerals surrounding porous defects.Its mechanical properties are determined using the mixed multi-inclusion method.Transformation of the bonded medium into the frictional medium occurs through crack extension,with its elastoplastic properties defined by the DruckerePrager yield criterion,accounting for hardening,softening,and extension.MorieTanaka and Eshelby’s equivalent inclusion methods are applied to the bonded and frictional media,respectively.The macroscopic mechanical properties of the rock are derived from these mesoscopic media.Consequently,a True Triaxial Macro-Mesoscopic(TTMM)constitutive model is developed.This model effectively captures the competitive effect and accurately describes the stress-deformation characteristics of granite.Utilizing the TTMM model,the strains resulting from porous defect closure and induced crack extension are differentiated,enabling quantitative determination of the associated damage evolution.展开更多
We consider that a low-frequency, sinusoidal rhythm detected by Electronic Fetal Monitoring (EFM) is a typical manifestation of a placental abruption. We present the case of a 26-year-old woman who was gestational 36 ...We consider that a low-frequency, sinusoidal rhythm detected by Electronic Fetal Monitoring (EFM) is a typical manifestation of a placental abruption. We present the case of a 26-year-old woman who was gestational 36 weeks. She had irregular contractions. The EFM showed a low-frequency, sinusoidal rhythm. The cycle of the sine curve increased in time from 90 seconds to 160 seconds gradually. A severely asphyxiated newborn was successfully resuscitated after an emergency Cesarean Section. The mother and child were discharged from our hospital in a good general condition seven days later. Upon examination it was proven that this was a case of a placental abruption. This is an original case study report about how to diagnose a placental abruption according to an EFM reading. We propose a definition of a low-frequency, sinusoidal rhythm having: 1) a stable baseline FHR (fetal heart rate) of 120 - 160 bpm;2) a possible variation of 20 - 30 bpm;3) a frequency of 90 - 160 seconds per cycle;4) fixed or flat short-term variability;5) oscillation of the sinusoidal wave from above and below a baseline;6) no areas of normal FHR variability or reactivity. What is more, the lengths of the fluctuation cycle and the greater the amplitude has a close relationship with the prognosis of both mother and child. This pre-partum, low-frequency, sinusoidal rhythm is an ominous sign of fetal jeopardy needing immediate intervention. The medical literature has never reported such an association. Therefore, our case study report is possibly the first to mention this observation.展开更多
Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potentia...Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potential,unfortunately,they have a low stability that hinders their clinical usage.Our earlier work revealed that Panax notoginseng derived exosome like nanoparticles,namely PDNs have potential to bypass BBB and reduce the cerebral ischemia/reperfusion(CI/R)damage.In this study,we employed microRNA-124 as a model therapeutic gene,utilizing its engineered variant Agomir-124(Ago124)to optimize loading efficiency.The therapeutic effects of Ago124@R-PDN were further assessed in several sets of experiments.Pharmacokinetic study showed that erythrocyte membrane extended the half-life of PDNs from 7 min to 11.3 h,and the loading efficiency of Ago124 reached 40%.In an in vitro oxygen-glucose deprivation/reperfusion(OGD/R)model,Ago124@R-PDN enhanced IL-10 production in microglia by 67%(vs 11.7%with free Ago124),and promoted Tuj1+neuronal differentiation by 2.23-fold compared with vehicle.Also,Ago124@R-PDN brought gene cargo into the brain,alleviated infarct volume,and improved functional behaviors in model mice.At last,we demonstrated that surface glycosyl of PDN facilitated its brain-entering ability by being recognized by sodium-glucose linked transporter-1 protein.In conclusion,our erythrocyte fused PDNs offer a promising strategy for delivering biomacromolecule to treat brain diseases.展开更多
Safe operation of underground reservoirs in coal mines is crucial for the coordinated exploitation of coal and water resources in western China.Mine water infiltration significantly influences the stability of the coa...Safe operation of underground reservoirs in coal mines is crucial for the coordinated exploitation of coal and water resources in western China.Mine water infiltration significantly influences the stability of the coal pillar.Therefore,laboratory tests were systematically carried out on coal from the Daliuta Coal Mine in Northwest China.Samples were taken in the vertical and parallel bedding directions and soaked for 0 d,2 d,4 d,or 16 d.In this study,atomic absorption spectroscopy(AAS),X-ray diffraction(XRD),and scanning electron microscopy(SEM)were used to analyze the variations in the water absorption characteristics and corresponding internal structure of the coal.Uniaxial compression tests and synchronous acoustic emission(AE)monitoring revealed the sample failure process and mechanical properties of the samples.Finally,the time-and frequency-domain characteristics of the AE signal were comprehensively analyzed using fractal dimension,fast Fourier transform,and cluster analysis.The strength and elastic modulus demonstrate significant anisotropy with different bedding planes and reveal the existence of the optimum water content.Specifically,the sample strength increases after 2 d of immersion,with increments of 23.3% and 0.6% for the vertical and parallel bedding samples,and decreases after 16 d of immersion,with decreases of 29% and 45% for the vertical and parallel samples,respectively.Additionally,shear cracks account for over 60% during the damage development of the samples.The proportion of tensile cracks is higher for samples with longer immersion times and parallel bedding planes.This research provides a theoretical basis for stability evaluation and protection of coal pillars in underground reservoirs using the AE technique.展开更多
The deep underground engineering will face high-temperature and ultrahigh-pressure(HTUP)condition.Indoor triaxial testing is an important means to investigate this challenge in rock mechanics and rock engineering.Heat...The deep underground engineering will face high-temperature and ultrahigh-pressure(HTUP)condition.Indoor triaxial testing is an important means to investigate this challenge in rock mechanics and rock engineering.Heat-shrinkable tubing,as a seal on the rock surface,is crucial for reconstructing deep rock in situ conditions(ensuring the accuracy and effectiveness of confining pressure and pore pressure).However,there are few reports on testing such material under HTUP condition.Thus,the mechanical and sealing performances of existing heat-shrinkable tubing under HTUP condition is still immature.The motivation of this study is to advance deep rock mechanics and engineering by developing a polymer heat-shrinkable tubing(pressure larger than 140 MPa and temperature greater than 150℃).Experiments using the deep rock in situ thermal insulation coring test system were conducted and compared with conventional heat-shrinkable tubing.The sealing performance of the polymer heat-shrinkable tubing was investigated.The results indicated that deep rock ultrahigh-pressure condition and natural damage to the rock surface are the main causes of conventional heat-shrinkable tubing failure.In contrast,the damage rate of the proposed polymer heat-shrinkable tubing is extremely low,indicating that incorporating base material with high-performances can significantly enhance the pressure resistance of polymer heat-shrinkable tubing.Additionally,through the analysis of experimental results and the three-dimensional(3D)morphology of rock surfaces,the failure behavior of heat-shrinkable tubing under HTUP condition was revealed at the meso-structural level,and the proposed failure criteria,taking into account 3D morphology of rock surfaces and applicable to HTUP condition,have been advanced.The findings offer possibilities for triaxial rock mechanics testing in HTUP condition,providing theoretical and technical support for experiments and engineering applications in deep rock mechanics.展开更多
Deep rocks encountered in underground engineering are frequently in complex in situ environments and experience both excavation disturbance during construction and cyclic loading throughout the long-term operation. Un...Deep rocks encountered in underground engineering are frequently in complex in situ environments and experience both excavation disturbance during construction and cyclic loading throughout the long-term operation. Understanding the fatigue behavior of excavation-disturbed rocks in complex stress environments is critical for assessing the long-term stability of deep rock structures. Hence, an experimental method has been developed to capture the fatigue damage process of rocks while considering the in situ environment and excavation disturbance. Using this method, a series of triaxial fatigue damage experiments were conducted on Jinping deep marble samples from various in situ environments of 100 m, 1000 m, 1800 m, and 2400 m to better understand the variation in fatigue characteristics at different depths. With increasing depth, the samples experienced more cycles and greater fatigue deformation before failure. Further insights were gained into the fatigue damage behavior in terms of stiffness degradation, energy dissipation and irreversible strain accumulation. A decrease in the elastic modulus and an increase in the dissipated energy and irreversible strain exhibit an evolution pattern of initial→stabilization→acceleration, reflecting the nonlinear fatigue process that occurs inside marble. With increasing depth, marble samples have longer fatigue lives but exhibit more significant stiffness loss, energy dissipation and irrecoverable deformation accumulation;thus, evaluating the instability of deep rock structures solely using fatigue life alone is inadequate. Moreover, the previously reported inverted S-shaped evolution of fatigue damage was observed, and it was found that an increase in depth leads to an earlier onset of the accelerated fatigue damage stage with greater dominance of fatigue failure. Based on the nonlinear strain, loading cycle variable and fatigue life, a highly accurate nonlinear fatigue model was developed to describe the complete inverted S-shaped evolution pattern of fatigue damage, which demonstrated excellent practical implications for the theoretical characterization of anisotropic fatigue damage in disturbed Jinping marble.展开更多
This special issue of Deep Underground Science and Engineering(DUSE)showcases pioneering research on the transformative role of machine learning(ML)and Big Data in deep underground engineering.Edited by vip editors ...This special issue of Deep Underground Science and Engineering(DUSE)showcases pioneering research on the transformative role of machine learning(ML)and Big Data in deep underground engineering.Edited by vip editors Prof.Asoke Nandi(Brunel University of London,UK),Prof.Ru Zhang(Sichuan University,China),Prof.Tao Zhao(Chinese Academy of Sciences,China),and Prof.Tao Lei(Shaanxi University of Science and Technology,China),this issue highlights the innovative applications of ML technique in reshaping structural safety,tunneling operations,and geotechnical investigations.展开更多
Radix Astragali has been an important traditional Chinese herbal medicine for over 2000 years. It is derived from two plant species, namely, Astragalus mongholicus [Astragalus membranaceus (Fisch.) Bge. var. mongholic...Radix Astragali has been an important traditional Chinese herbal medicine for over 2000 years. It is derived from two plant species, namely, Astragalus mongholicus [Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao] and Astragalus membranaceus [Astragalus membranaceus (Fisch.) Bge.] (Leguminosae ), according to the Pharmacopoeia of the People’s Republic of China. In this study, the genetic diversity and genetic relationships of Radix Astragali in China were analyzed by Inter-Simple Sequence Repeat (ISSR) markers. A total of 25 highly polymorphic ISSR primers were selected to amplify 95 Radix Astragali samples. Among 273 DNA bands amplified, 213 are polymorphic (percentage of polymorphic bands: 78%). The average value of the amplified bands was 10.9 for each primer, and the number varied from 4 to 20. The genetic diversity of the 95 Radix Astragali samples was analyzed by using POPGENE 1.32 software. The Nei’s genetic diversity index (h) and Shannon’s information index (I ) were 0.3590 and 0.5308, respectively, which indicated the abundant genetic diversity of Radix Astragali . The level of genetic diversity in A. membranaceus (h: 0.3109, I : 0.4657) was slightly lower than that in A. mongholicus (h: 0.3364, I : 0.4969). Considering the average genetic similarity coefficient by NTSYS analysis to cluster the A. membranaceus of nine habitats and A. mongholicus of five habitats, Radix Astragali samples were clustered into two groups according to place of origin. This clustering is different from traditional clustering, which divides groups according to species. Results obtained from this study will provide a theoretical basis for the molecular study on germplasm resources of Radix Astragali .展开更多
Heavy metals have been viewed as hazardous environmental pollutants, and anthropogenic activities due to their high toxicity and persistent nature in the environment. Anthropogenic activities such as artisanal mining,...Heavy metals have been viewed as hazardous environmental pollutants, and anthropogenic activities due to their high toxicity and persistent nature in the environment. Anthropogenic activities such as artisanal mining, industrial activities, improper usage of fertilizers and pesticides, and indiscriminate open waste disposal bring about an increase in the presence of heavy metals in the environment. In the Keffi Metropolis, different elements lead to land contamination which debilitates soil quality, plant survival, human well-being, and the environment as a result of extensive dispersion or quantity of heavy metals in the soil and water. In recent years, biochar has emerged as a promising soil amendment for mitigating heavy metal pollution due to its unique physicochemical properties. This paper provides the effects of softwood pellet biochar on the retention of heavy metals in contaminated soils. A microcosm experiment was carried out to investigate the effects of biochar on the retention of heavy metals in contaminated soils. This research aimed to give an overview of the effects of softwood biochar at different temperatures (550˚C and 700˚C) on the retention of heavy metals and metalloids released from the soil during water inundation. The results show that the addition of organic matter (grass chippings) minimizes heavy metal mobilization. Also, biochar at high temperatures is more effective than those at low temperatures. The expected outcome of the research analysis includes providing insights into the role of biochar in retaining heavy metal contamination and further understanding the use of biochar as a sorbent for the management of contaminated soil.展开更多
基金supported by the National Natural Science Foundation of China (No. 82074277 and 81773911)the Development Project of Shanghai Peak Disciplines-Integrated Medicine (No. 20180101)
文摘To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of liposomes.The results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their liposomes.The pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in vivo.The C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 cells.According to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting capabilities.The results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.
基金Project supported by the National Natural Science Foundation of China(Nos.50908202,51178426,90915008,and 60801011)the Zhejiang Provincial Natural Science Foundation,China(No.Y1090382)+1 种基金the Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China(No.122012)the Key Science and Technology Innovation Team Program of Zhejiang Province,China(No.2010R50034)
文摘Steel structures are widely used in railway infrastructures.Their stress state is the most important determinant of the safety of these structures.The elasto-magnetic (EM) sensor is the most promising for stress monitoring of in-service steel structures.Nevertheless,the necessity of magnetic excitation to saturation due to the use of a secondary coil for signal detection,keeps from its engineering application.In this paper,a smart elasto-magneto-electric (EME) sensor using magneto-electric (ME) sensing units to take the place of the secondary coil has been exploited for the first time.The ME sensing unit is made of ME laminated composites,which has an ultrahigh ME voltage coefficient and can measure the magnetic induction simply and precisely.Theoretical analysis and characterization experiments firstly conducted on the ME laminated composites showed that the ME sensing units can be applied in the EM sensor for improved performance in stress monitoring.A tension test of a steel bar was carried out to characterize our smart EME sensor and the results showed high accuracy and sensitivity.The present smart EME sensor is a promising tool for stress monitoring of steel structures in railway and other civil infrastructures.
文摘An in vitro blood-brain barrier(BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous system.Though many models have been developed, their reproducibility and renewability remain a challenge. Furthermore, drug transport data from many of the models do not correlate well with the data for in vivo BBB drug transport.Induced-pluripotent stem cell(i PSC) technology provides reproducible cell resources for in vitro BBB modeling.Here, we generated a human in vitro BBB model by differentiating the human i PSC(hi PSC) line GM25256 into brain endothelial-type cells. The model displayed BBB characteristics including tight junction proteins(ZO-1,claudin-5, and occludin) and endothelial markers(von Willebrand factor and Ulex), as well as high transendothelial electrical resistance(TEER)(1560 X.cm2±230 X.cm2) and c-GTPase activity. Co-culture with primary rat astrocytes significantly increased the TEER of the model(2970 X.cm2 to 4185 X.cm2). RNAseq analysis confirmed the expression of key BBB-related genes in the hi PSC-derived endothelial cells in comparison with primary human brain microvascular endothelial cells,including P-glycoprotein(Pgp) and breast cancer resistant protein(BCRP). Drug transport assays for nine CNS compounds showed that the permeability of non-Pgp/BCRP and Pgp/BCRP substrates across the model was strongly correlated with rodent in situ brain perfusion data for these compounds(R2= 0.982 and R2= 0.9973,respectively), demonstrating the functionality of the drug transporters in the model. Thus, this model may be used to rapidly screen CNS compounds, to predict the in vivo BBB permeability of these compounds and to study the biology of the BBB.
基金funding support from the National Natural Science Foundation of China(Grant No.U1965203)“Dynamic analysis method of complex rock underground engineering in the Hengduan Mountains”project(Grant No.P43419)the Sichuan University Postdoctoral Research Fund(Grant No.2023SCU12123).
文摘The complex mechanical and damage mechanisms of rocks are intricately tied to their diverse mineral compositions and the formation of pores and cracks under external loads.Numerous rock tests reveal a complex interplay between the closure of porous defects and the propagation of induced cracks,presenting challenges in accurately representing their mechanical properties,especially under true triaxial stress conditions.This paper proposes a conceptualization of rock at the mesoscopic level as a two-phase composite,consisting of a bonded medium matrix and frictional medium inclusions.The bonded medium is characterized as a mesoscopic elastic material,encompassing various minerals surrounding porous defects.Its mechanical properties are determined using the mixed multi-inclusion method.Transformation of the bonded medium into the frictional medium occurs through crack extension,with its elastoplastic properties defined by the DruckerePrager yield criterion,accounting for hardening,softening,and extension.MorieTanaka and Eshelby’s equivalent inclusion methods are applied to the bonded and frictional media,respectively.The macroscopic mechanical properties of the rock are derived from these mesoscopic media.Consequently,a True Triaxial Macro-Mesoscopic(TTMM)constitutive model is developed.This model effectively captures the competitive effect and accurately describes the stress-deformation characteristics of granite.Utilizing the TTMM model,the strains resulting from porous defect closure and induced crack extension are differentiated,enabling quantitative determination of the associated damage evolution.
文摘We consider that a low-frequency, sinusoidal rhythm detected by Electronic Fetal Monitoring (EFM) is a typical manifestation of a placental abruption. We present the case of a 26-year-old woman who was gestational 36 weeks. She had irregular contractions. The EFM showed a low-frequency, sinusoidal rhythm. The cycle of the sine curve increased in time from 90 seconds to 160 seconds gradually. A severely asphyxiated newborn was successfully resuscitated after an emergency Cesarean Section. The mother and child were discharged from our hospital in a good general condition seven days later. Upon examination it was proven that this was a case of a placental abruption. This is an original case study report about how to diagnose a placental abruption according to an EFM reading. We propose a definition of a low-frequency, sinusoidal rhythm having: 1) a stable baseline FHR (fetal heart rate) of 120 - 160 bpm;2) a possible variation of 20 - 30 bpm;3) a frequency of 90 - 160 seconds per cycle;4) fixed or flat short-term variability;5) oscillation of the sinusoidal wave from above and below a baseline;6) no areas of normal FHR variability or reactivity. What is more, the lengths of the fluctuation cycle and the greater the amplitude has a close relationship with the prognosis of both mother and child. This pre-partum, low-frequency, sinusoidal rhythm is an ominous sign of fetal jeopardy needing immediate intervention. The medical literature has never reported such an association. Therefore, our case study report is possibly the first to mention this observation.
基金supported by National Natural Science Foundation of China(82374296,82271965,62331021)Development Project of Shanghai Peak Disciplines-Integrated Medicine(201801)+1 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)Shanghai Municipal Science and Technology Explorer Project(23TS1400500).
文摘Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potential,unfortunately,they have a low stability that hinders their clinical usage.Our earlier work revealed that Panax notoginseng derived exosome like nanoparticles,namely PDNs have potential to bypass BBB and reduce the cerebral ischemia/reperfusion(CI/R)damage.In this study,we employed microRNA-124 as a model therapeutic gene,utilizing its engineered variant Agomir-124(Ago124)to optimize loading efficiency.The therapeutic effects of Ago124@R-PDN were further assessed in several sets of experiments.Pharmacokinetic study showed that erythrocyte membrane extended the half-life of PDNs from 7 min to 11.3 h,and the loading efficiency of Ago124 reached 40%.In an in vitro oxygen-glucose deprivation/reperfusion(OGD/R)model,Ago124@R-PDN enhanced IL-10 production in microglia by 67%(vs 11.7%with free Ago124),and promoted Tuj1+neuronal differentiation by 2.23-fold compared with vehicle.Also,Ago124@R-PDN brought gene cargo into the brain,alleviated infarct volume,and improved functional behaviors in model mice.At last,we demonstrated that surface glycosyl of PDN facilitated its brain-entering ability by being recognized by sodium-glucose linked transporter-1 protein.In conclusion,our erythrocyte fused PDNs offer a promising strategy for delivering biomacromolecule to treat brain diseases.
基金supported by the National Natural Science Foundation of China(Grant Nos.52174084 and U23B20146)the Open Fund for State Key Laboratory of Water Resource Protection and Utilization in Coal Mining(Grant No.WPUKFJJ2022-07)。
文摘Safe operation of underground reservoirs in coal mines is crucial for the coordinated exploitation of coal and water resources in western China.Mine water infiltration significantly influences the stability of the coal pillar.Therefore,laboratory tests were systematically carried out on coal from the Daliuta Coal Mine in Northwest China.Samples were taken in the vertical and parallel bedding directions and soaked for 0 d,2 d,4 d,or 16 d.In this study,atomic absorption spectroscopy(AAS),X-ray diffraction(XRD),and scanning electron microscopy(SEM)were used to analyze the variations in the water absorption characteristics and corresponding internal structure of the coal.Uniaxial compression tests and synchronous acoustic emission(AE)monitoring revealed the sample failure process and mechanical properties of the samples.Finally,the time-and frequency-domain characteristics of the AE signal were comprehensively analyzed using fractal dimension,fast Fourier transform,and cluster analysis.The strength and elastic modulus demonstrate significant anisotropy with different bedding planes and reveal the existence of the optimum water content.Specifically,the sample strength increases after 2 d of immersion,with increments of 23.3% and 0.6% for the vertical and parallel bedding samples,and decreases after 16 d of immersion,with decreases of 29% and 45% for the vertical and parallel samples,respectively.Additionally,shear cracks account for over 60% during the damage development of the samples.The proportion of tensile cracks is higher for samples with longer immersion times and parallel bedding planes.This research provides a theoretical basis for stability evaluation and protection of coal pillars in underground reservoirs using the AE technique.
基金funding provided by the National Natural Science Foundation of China(Grant Nos.51827901 and 52174084)the Natural Science Foundation of Sichuan Provence,China(Grant No.2022NSFSC0005).
文摘The deep underground engineering will face high-temperature and ultrahigh-pressure(HTUP)condition.Indoor triaxial testing is an important means to investigate this challenge in rock mechanics and rock engineering.Heat-shrinkable tubing,as a seal on the rock surface,is crucial for reconstructing deep rock in situ conditions(ensuring the accuracy and effectiveness of confining pressure and pore pressure).However,there are few reports on testing such material under HTUP condition.Thus,the mechanical and sealing performances of existing heat-shrinkable tubing under HTUP condition is still immature.The motivation of this study is to advance deep rock mechanics and engineering by developing a polymer heat-shrinkable tubing(pressure larger than 140 MPa and temperature greater than 150℃).Experiments using the deep rock in situ thermal insulation coring test system were conducted and compared with conventional heat-shrinkable tubing.The sealing performance of the polymer heat-shrinkable tubing was investigated.The results indicated that deep rock ultrahigh-pressure condition and natural damage to the rock surface are the main causes of conventional heat-shrinkable tubing failure.In contrast,the damage rate of the proposed polymer heat-shrinkable tubing is extremely low,indicating that incorporating base material with high-performances can significantly enhance the pressure resistance of polymer heat-shrinkable tubing.Additionally,through the analysis of experimental results and the three-dimensional(3D)morphology of rock surfaces,the failure behavior of heat-shrinkable tubing under HTUP condition was revealed at the meso-structural level,and the proposed failure criteria,taking into account 3D morphology of rock surfaces and applicable to HTUP condition,have been advanced.The findings offer possibilities for triaxial rock mechanics testing in HTUP condition,providing theoretical and technical support for experiments and engineering applications in deep rock mechanics.
基金funded by the National Natural Science Foundation of China(Grant No.U23B20146)the Natural Science Foundation of Sichuan Province,China(Grant Nos.2024NSFSC0825 and 2022NSFSC0406)We are also grateful for the support provided by the China Scholarship Council(CSC).
文摘Deep rocks encountered in underground engineering are frequently in complex in situ environments and experience both excavation disturbance during construction and cyclic loading throughout the long-term operation. Understanding the fatigue behavior of excavation-disturbed rocks in complex stress environments is critical for assessing the long-term stability of deep rock structures. Hence, an experimental method has been developed to capture the fatigue damage process of rocks while considering the in situ environment and excavation disturbance. Using this method, a series of triaxial fatigue damage experiments were conducted on Jinping deep marble samples from various in situ environments of 100 m, 1000 m, 1800 m, and 2400 m to better understand the variation in fatigue characteristics at different depths. With increasing depth, the samples experienced more cycles and greater fatigue deformation before failure. Further insights were gained into the fatigue damage behavior in terms of stiffness degradation, energy dissipation and irreversible strain accumulation. A decrease in the elastic modulus and an increase in the dissipated energy and irreversible strain exhibit an evolution pattern of initial→stabilization→acceleration, reflecting the nonlinear fatigue process that occurs inside marble. With increasing depth, marble samples have longer fatigue lives but exhibit more significant stiffness loss, energy dissipation and irrecoverable deformation accumulation;thus, evaluating the instability of deep rock structures solely using fatigue life alone is inadequate. Moreover, the previously reported inverted S-shaped evolution of fatigue damage was observed, and it was found that an increase in depth leads to an earlier onset of the accelerated fatigue damage stage with greater dominance of fatigue failure. Based on the nonlinear strain, loading cycle variable and fatigue life, a highly accurate nonlinear fatigue model was developed to describe the complete inverted S-shaped evolution pattern of fatigue damage, which demonstrated excellent practical implications for the theoretical characterization of anisotropic fatigue damage in disturbed Jinping marble.
文摘This special issue of Deep Underground Science and Engineering(DUSE)showcases pioneering research on the transformative role of machine learning(ML)and Big Data in deep underground engineering.Edited by vip editors Prof.Asoke Nandi(Brunel University of London,UK),Prof.Ru Zhang(Sichuan University,China),Prof.Tao Zhao(Chinese Academy of Sciences,China),and Prof.Tao Lei(Shaanxi University of Science and Technology,China),this issue highlights the innovative applications of ML technique in reshaping structural safety,tunneling operations,and geotechnical investigations.
文摘Radix Astragali has been an important traditional Chinese herbal medicine for over 2000 years. It is derived from two plant species, namely, Astragalus mongholicus [Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao] and Astragalus membranaceus [Astragalus membranaceus (Fisch.) Bge.] (Leguminosae ), according to the Pharmacopoeia of the People’s Republic of China. In this study, the genetic diversity and genetic relationships of Radix Astragali in China were analyzed by Inter-Simple Sequence Repeat (ISSR) markers. A total of 25 highly polymorphic ISSR primers were selected to amplify 95 Radix Astragali samples. Among 273 DNA bands amplified, 213 are polymorphic (percentage of polymorphic bands: 78%). The average value of the amplified bands was 10.9 for each primer, and the number varied from 4 to 20. The genetic diversity of the 95 Radix Astragali samples was analyzed by using POPGENE 1.32 software. The Nei’s genetic diversity index (h) and Shannon’s information index (I ) were 0.3590 and 0.5308, respectively, which indicated the abundant genetic diversity of Radix Astragali . The level of genetic diversity in A. membranaceus (h: 0.3109, I : 0.4657) was slightly lower than that in A. mongholicus (h: 0.3364, I : 0.4969). Considering the average genetic similarity coefficient by NTSYS analysis to cluster the A. membranaceus of nine habitats and A. mongholicus of five habitats, Radix Astragali samples were clustered into two groups according to place of origin. This clustering is different from traditional clustering, which divides groups according to species. Results obtained from this study will provide a theoretical basis for the molecular study on germplasm resources of Radix Astragali .
文摘Heavy metals have been viewed as hazardous environmental pollutants, and anthropogenic activities due to their high toxicity and persistent nature in the environment. Anthropogenic activities such as artisanal mining, industrial activities, improper usage of fertilizers and pesticides, and indiscriminate open waste disposal bring about an increase in the presence of heavy metals in the environment. In the Keffi Metropolis, different elements lead to land contamination which debilitates soil quality, plant survival, human well-being, and the environment as a result of extensive dispersion or quantity of heavy metals in the soil and water. In recent years, biochar has emerged as a promising soil amendment for mitigating heavy metal pollution due to its unique physicochemical properties. This paper provides the effects of softwood pellet biochar on the retention of heavy metals in contaminated soils. A microcosm experiment was carried out to investigate the effects of biochar on the retention of heavy metals in contaminated soils. This research aimed to give an overview of the effects of softwood biochar at different temperatures (550˚C and 700˚C) on the retention of heavy metals and metalloids released from the soil during water inundation. The results show that the addition of organic matter (grass chippings) minimizes heavy metal mobilization. Also, biochar at high temperatures is more effective than those at low temperatures. The expected outcome of the research analysis includes providing insights into the role of biochar in retaining heavy metal contamination and further understanding the use of biochar as a sorbent for the management of contaminated soil.