Rehmannia glutinosa root is one of the most commonly used herbs in traditional Chinese medicine. It has a long history in East and Southeast Asian countries for relieving heat and cooling the blood, nourishing yin and...Rehmannia glutinosa root is one of the most commonly used herbs in traditional Chinese medicine. It has a long history in East and Southeast Asian countries for relieving heat and cooling the blood, nourishing yin and body fluid.展开更多
The 27th Session of United Nations Commission on Science and Technology for Development(CSTD)was held on April 15-19.The side event“Shaping the Future of AI”on April 16 was hosted by the World Digital Technology Aca...The 27th Session of United Nations Commission on Science and Technology for Development(CSTD)was held on April 15-19.The side event“Shaping the Future of AI”on April 16 was hosted by the World Digital Technology Academy(WDTA),an NGO that promotes digital technologies and global cooperation,where breakthrough results including two standards were released.展开更多
Recent progress in calculating gas bubble sizes in a plume, based on phenomenological approaches using the release conditions is a significant improvement to make the gas plume models self-reliant. Such calculations r...Recent progress in calculating gas bubble sizes in a plume, based on phenomenological approaches using the release conditions is a significant improvement to make the gas plume models self-reliant. Such calculations require details of conditions Near the Source of Plume (NSP); (i.e. the plume/jet velocity and radius near the source), which inspired the present work. Determining NSP conditions for gas plumes are far more complex than that for oil plumes due to the substantial density difference between gas and water. To calculate NSP conditions, modeling the early stage of the plume is important. A novel method of modeling the early stage of an underwater gas release is presented here. Major impact of the present work is to define the correct NSP conditions for underwater gas releases, which is not possible with available methods as those techniques are not based on the physics of flow region near the source of the plume/jet. We introduce super Gaussian profiles to model the density and velocity variations of the early stages of plume, coupled with the laws of fluid mechanics to define profile parameters. This new approach, models the velocity profile variation from near uniform, across the section at the release point to Gaussian some distance away. The comparisons show that experimental data agrees well with the computations.展开更多
Oil droplet size distribution (ODSD) plays a critical role in the rising velocity and transport of oil droplets in subsurface oil releases. In this paper, subsurface oil release experiments were conducted to study O...Oil droplet size distribution (ODSD) plays a critical role in the rising velocity and transport of oil droplets in subsurface oil releases. In this paper, subsurface oil release experiments were conducted to study ODSD under different experimental conditions in a laboratory water tank observed by two high-speed cameras in March and April 2017. The correlation formulas Oh=lO.2Re-~ and Oh=39.2Re-1 (Re represents Reynolds number and Oh represents Ohnesorge number) were established to distinguish the boundaries of the three instability regimes in dimensionless space based on the experimental results. The oil droplet sizes from the experimental data showed an excellent match to the Rosin-Rammler distribution function with determination coefficients ranging from 0.86 to 1.00 for Lvda 10-1 oil. This paper also explored the influence factors on and change rules ofoil droplet size. The volume median diameter d50 decreased steadily with increasing jet velocity, and a sharp decrease occurred in the laminar-breakup regime. At Weber numbers (We) 〈100, the orifice diameter and oil viscosity appeared to have a large influence on the mean droplet diameter. At 100〈We〈1 000, the oil viscosity appeared to have a larger influence on the relative mean droplet diameter.展开更多
"Being responsible is not only the right thins to do-it also makes perfect business sense."H&M Hennes & Mauritz AB has published"Style & Substance",its sustainability report for 2009.
Gerber Technology, a business unit of Gerber Scientific, Inc. (NYSE: GRB) and the world leader in automated CAD/CAM and PLM solutions for the apparel and flexible materials industry, introduced two new software offeri...Gerber Technology, a business unit of Gerber Scientific, Inc. (NYSE: GRB) and the world leader in automated CAD/CAM and PLM solutions for the apparel and flexible materials industry, introduced two new software offerings –展开更多
Color trend insights extremely benefit textile and fashion industries What is the next big Trend? This is not just the question to get dressed in trend. But trends information is highly essential for designers
The paper presents a brief summary of the introduction of the term “practical elimination” as prevention of the conditions that could lead to early or large radioactive releases. The concept of “practical eliminat...The paper presents a brief summary of the introduction of the term “practical elimination” as prevention of the conditions that could lead to early or large radioactive releases. The concept of “practical elimination” is defined as part of the Defence in Depth (DiD) of Nuclear Power Plant (NPP) in the International Atomic Energy Agency (IAEA) document INSAG-12 in 1999. But, the special attention to it was paid after the accident in Fukushima NPP in 2011. The mechanisms of the containment failure of reactor WWER-1000/V320 are presented. As an example, the summarized design features and preventing and mitigation measures already implemented at Kozloduy NPP to extend the design basis and beyond design basis envelop are presented. Issues related to external steam explosion are underlined for further study.展开更多
The Mediterranean fruit fly (Medfly), Ceratitis capitata (Wiedemann) is one of the major pests of fruit crops in Argentina and it is a phytosanitary barrier to the export of fresh fruits. In the Province of San Juan, ...The Mediterranean fruit fly (Medfly), Ceratitis capitata (Wiedemann) is one of the major pests of fruit crops in Argentina and it is a phytosanitary barrier to the export of fresh fruits. In the Province of San Juan, located in the central-eastern region of Argentina known as Cuyo, control strategies against Medfly in fruit-producing irrigated-valleys have been implemented by the National Fruit Fly Control and Eradication Program (ProCEM) jointly with the provincial government and the producers. This program uses an area-wide integrated pest management approach that includes the use of environment-friendly strategies to suppress or eradicate Medfly, such as the use of the sterile insect technique and the application of new-generation bait sprays, and more recently the release of the Indo-Pacific parasitoid Diachasmimorpha longicaudata (Ashmead). This exotic larval-prepupal endoparasitoid is being mass-reared on larvae of Vienna 8 TSL C. capitata strain at the BioPlanta San Juan facility. In this respect, the objective of this study was to assess the effectiveness of laboratory-reared D. longicaudata females in order to find and successfully parasitize Medfly larvae in different host fruit species once released under semi-arid environmental conditions in ecologically isolated fruit-growing valleys of San Juan. Ground releases were used to disperse parasitoids in 6 fruit-producing valleys. In total, 40,000 adult parasitoids were released at places with various Medfly host plants bearing fruits and in which no insecticides were regularly applied, such as backyards and small orchards. 119 D. longicaudata adults were recovered from 6 Medfly-infested fruit species that were collected in 5 release sites (Pocito, Zonda, Santa Lucía, Caucete, and Rivadavia). The highest number of parasitoids was recovered from fig, followed by grape, rose, orange, tangerine, and persimmon. Data provided from this study open up the possibility of implementing a parasitoid mass-release program in San Juan.展开更多
Since the outbreak of COVID-19,CIIS has been closely following the development of the pandemic and the responses from China and the rest of the world,and released a series of nine reports collaboratively completed by ...Since the outbreak of COVID-19,CIIS has been closely following the development of the pandemic and the responses from China and the rest of the world,and released a series of nine reports collaboratively completed by CIIS researchers across departments so far.展开更多
On March 2,2022,the World Tourism Cities Federation(WTCF)and the Tourism Research Centre,Chinese Academy of Social Sciences(TRC-CASS)jointly released the World Tourism Economy Trends Report(2022)(hereinafter referred ...On March 2,2022,the World Tourism Cities Federation(WTCF)and the Tourism Research Centre,Chinese Academy of Social Sciences(TRC-CASS)jointly released the World Tourism Economy Trends Report(2022)(hereinafter referred to as the Report)in Beijing.展开更多
The Carbon Peak Carbon Neutral Forum 2022 and the Shenzhen International Low Carbon City Forum was held on December 13,which gathered renowned global experts and representatives of institutes,leading enterprises and i...The Carbon Peak Carbon Neutral Forum 2022 and the Shenzhen International Low Carbon City Forum was held on December 13,which gathered renowned global experts and representatives of institutes,leading enterprises and international organizations.展开更多
China has released an updated national species database,known as the Catalogue of Life China 2022 Annual Checklist,according to the Chinese Academy of Sciences(CAS)on May 22.The checklist of this year added 10,343 spe...China has released an updated national species database,known as the Catalogue of Life China 2022 Annual Checklist,according to the Chinese Academy of Sciences(CAS)on May 22.The checklist of this year added 10,343 species compared with the 2021 checklist,bringing the total number of species to 138,293,including 68,172 animal species,46,725 plant species,and 17,173 fungi species,among others.The species checklist provides data basis that is beneficial for biodiversity research,conservation and policy-making,said an official with Biodiversity Committee under the CAS,adding that China is the only country that publishes the biological species checklist every year.展开更多
The problem investigated in this research is about the potential risk of technological hazards, which poses a perilous threat to humankind and the environment. Rapid urbanization has been increasing the population den...The problem investigated in this research is about the potential risk of technological hazards, which poses a perilous threat to humankind and the environment. Rapid urbanization has been increasing the population density in an area, elevating the risk of exposure to technological disasters. Therefore, it is necessary to detect the areas with higher chemical risk to spread awareness about the potential risk zones and reduce actual damage and casualties resulting from the hazardous substance events. The basic design of the study utilizes geospatial analysis to map the TRI (Toxics Release Inventory) facilities in the communities of Texas to establish a relationship between potential </span><span style="font-family:Verdana;">hazardous material release zones and the human population at risk. The</span><span style="font-family:Verdana;"> study identified the vulnerable counties as well as investigated how those risk areas are related to race/ethnicity, income and education. The research would contribute to the policymakers acting on the hazard situation and keep them better prepared for</span><span style="color:red;"> </span><span style="font-family:Verdana;">chemical hazards. In addition, it would help the residents and emergency managers to better understand the circumstance to mitigate the consequences as well as increase their awareness to be ready for the uncertainties in the hotspots involved in high risk of the hazards.展开更多
General Aviation Manufacturers Association released the 2023 General Aviation Aircraft Shipments and Billings Report during its annual State of the Industry Press Conference.Overall,when compared to 2022,all aircraft ...General Aviation Manufacturers Association released the 2023 General Aviation Aircraft Shipments and Billings Report during its annual State of the Industry Press Conference.Overall,when compared to 2022,all aircraft segments saw increases in shipments and preliminary aircraft deliveries were valued at$27.8 billion,an increase of 3.6%.展开更多
China's State Council on December 7 released a plan on highlevel institutional opening-up in the Shanghai Free Trade Zone,proposing to build Shanghai into a demonstration area for national institutional opening-up...China's State Council on December 7 released a plan on highlevel institutional opening-up in the Shanghai Free Trade Zone,proposing to build Shanghai into a demonstration area for national institutional opening-up and deepened reforms.展开更多
As an effective means to actively modify the ionosphere, chemical release can produce artificial ionospheric holes as a consequence of ionization depletion, which can greatly impact on radio wave propagation. In this ...As an effective means to actively modify the ionosphere, chemical release can produce artificial ionospheric holes as a consequence of ionization depletion, which can greatly impact on radio wave propagation. In this paper, on the basis of the pre-study results on ionospheric disturbances produced by some representative chemical releases, the radio waves propagation effects of ionospheric holes that are produced by two different release species, water (H2O) and sulfur hexafluoride (SF6), had been investigated and simulated by the three-dimensional (3-D) numerical ray tracing. The results show that 1 the appearance of various artificial ionospheric holes can lead to certain decrease of critical frequency in the ionosphere, and 2 when the wave frequency exceeds the critical frequency, the rays should be multiple reflections or penetrate through the ionospheric hole and focus afterwards with the focus altitude elevated for higher frequencies. This work may provide the necessary theoretical support for chemical release experiments and the evaluation of radio wave propagation effects.展开更多
Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv...Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.展开更多
During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their el...During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination(the weakest in acetylcholine release and those that have already become silent).The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development.Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases.展开更多
文摘Rehmannia glutinosa root is one of the most commonly used herbs in traditional Chinese medicine. It has a long history in East and Southeast Asian countries for relieving heat and cooling the blood, nourishing yin and body fluid.
文摘The 27th Session of United Nations Commission on Science and Technology for Development(CSTD)was held on April 15-19.The side event“Shaping the Future of AI”on April 16 was hosted by the World Digital Technology Academy(WDTA),an NGO that promotes digital technologies and global cooperation,where breakthrough results including two standards were released.
文摘Recent progress in calculating gas bubble sizes in a plume, based on phenomenological approaches using the release conditions is a significant improvement to make the gas plume models self-reliant. Such calculations require details of conditions Near the Source of Plume (NSP); (i.e. the plume/jet velocity and radius near the source), which inspired the present work. Determining NSP conditions for gas plumes are far more complex than that for oil plumes due to the substantial density difference between gas and water. To calculate NSP conditions, modeling the early stage of the plume is important. A novel method of modeling the early stage of an underwater gas release is presented here. Major impact of the present work is to define the correct NSP conditions for underwater gas releases, which is not possible with available methods as those techniques are not based on the physics of flow region near the source of the plume/jet. We introduce super Gaussian profiles to model the density and velocity variations of the early stages of plume, coupled with the laws of fluid mechanics to define profile parameters. This new approach, models the velocity profile variation from near uniform, across the section at the release point to Gaussian some distance away. The comparisons show that experimental data agrees well with the computations.
基金The National Key Research and Development Program of China under contract No.2016YFC1402303
文摘Oil droplet size distribution (ODSD) plays a critical role in the rising velocity and transport of oil droplets in subsurface oil releases. In this paper, subsurface oil release experiments were conducted to study ODSD under different experimental conditions in a laboratory water tank observed by two high-speed cameras in March and April 2017. The correlation formulas Oh=lO.2Re-~ and Oh=39.2Re-1 (Re represents Reynolds number and Oh represents Ohnesorge number) were established to distinguish the boundaries of the three instability regimes in dimensionless space based on the experimental results. The oil droplet sizes from the experimental data showed an excellent match to the Rosin-Rammler distribution function with determination coefficients ranging from 0.86 to 1.00 for Lvda 10-1 oil. This paper also explored the influence factors on and change rules ofoil droplet size. The volume median diameter d50 decreased steadily with increasing jet velocity, and a sharp decrease occurred in the laminar-breakup regime. At Weber numbers (We) 〈100, the orifice diameter and oil viscosity appeared to have a large influence on the mean droplet diameter. At 100〈We〈1 000, the oil viscosity appeared to have a larger influence on the relative mean droplet diameter.
文摘"Being responsible is not only the right thins to do-it also makes perfect business sense."H&M Hennes & Mauritz AB has published"Style & Substance",its sustainability report for 2009.
文摘Gerber Technology, a business unit of Gerber Scientific, Inc. (NYSE: GRB) and the world leader in automated CAD/CAM and PLM solutions for the apparel and flexible materials industry, introduced two new software offerings –
文摘Color trend insights extremely benefit textile and fashion industries What is the next big Trend? This is not just the question to get dressed in trend. But trends information is highly essential for designers
文摘The paper presents a brief summary of the introduction of the term “practical elimination” as prevention of the conditions that could lead to early or large radioactive releases. The concept of “practical elimination” is defined as part of the Defence in Depth (DiD) of Nuclear Power Plant (NPP) in the International Atomic Energy Agency (IAEA) document INSAG-12 in 1999. But, the special attention to it was paid after the accident in Fukushima NPP in 2011. The mechanisms of the containment failure of reactor WWER-1000/V320 are presented. As an example, the summarized design features and preventing and mitigation measures already implemented at Kozloduy NPP to extend the design basis and beyond design basis envelop are presented. Issues related to external steam explosion are underlined for further study.
文摘The Mediterranean fruit fly (Medfly), Ceratitis capitata (Wiedemann) is one of the major pests of fruit crops in Argentina and it is a phytosanitary barrier to the export of fresh fruits. In the Province of San Juan, located in the central-eastern region of Argentina known as Cuyo, control strategies against Medfly in fruit-producing irrigated-valleys have been implemented by the National Fruit Fly Control and Eradication Program (ProCEM) jointly with the provincial government and the producers. This program uses an area-wide integrated pest management approach that includes the use of environment-friendly strategies to suppress or eradicate Medfly, such as the use of the sterile insect technique and the application of new-generation bait sprays, and more recently the release of the Indo-Pacific parasitoid Diachasmimorpha longicaudata (Ashmead). This exotic larval-prepupal endoparasitoid is being mass-reared on larvae of Vienna 8 TSL C. capitata strain at the BioPlanta San Juan facility. In this respect, the objective of this study was to assess the effectiveness of laboratory-reared D. longicaudata females in order to find and successfully parasitize Medfly larvae in different host fruit species once released under semi-arid environmental conditions in ecologically isolated fruit-growing valleys of San Juan. Ground releases were used to disperse parasitoids in 6 fruit-producing valleys. In total, 40,000 adult parasitoids were released at places with various Medfly host plants bearing fruits and in which no insecticides were regularly applied, such as backyards and small orchards. 119 D. longicaudata adults were recovered from 6 Medfly-infested fruit species that were collected in 5 release sites (Pocito, Zonda, Santa Lucía, Caucete, and Rivadavia). The highest number of parasitoids was recovered from fig, followed by grape, rose, orange, tangerine, and persimmon. Data provided from this study open up the possibility of implementing a parasitoid mass-release program in San Juan.
文摘Since the outbreak of COVID-19,CIIS has been closely following the development of the pandemic and the responses from China and the rest of the world,and released a series of nine reports collaboratively completed by CIIS researchers across departments so far.
文摘On March 2,2022,the World Tourism Cities Federation(WTCF)and the Tourism Research Centre,Chinese Academy of Social Sciences(TRC-CASS)jointly released the World Tourism Economy Trends Report(2022)(hereinafter referred to as the Report)in Beijing.
文摘The Carbon Peak Carbon Neutral Forum 2022 and the Shenzhen International Low Carbon City Forum was held on December 13,which gathered renowned global experts and representatives of institutes,leading enterprises and international organizations.
文摘China has released an updated national species database,known as the Catalogue of Life China 2022 Annual Checklist,according to the Chinese Academy of Sciences(CAS)on May 22.The checklist of this year added 10,343 species compared with the 2021 checklist,bringing the total number of species to 138,293,including 68,172 animal species,46,725 plant species,and 17,173 fungi species,among others.The species checklist provides data basis that is beneficial for biodiversity research,conservation and policy-making,said an official with Biodiversity Committee under the CAS,adding that China is the only country that publishes the biological species checklist every year.
文摘The problem investigated in this research is about the potential risk of technological hazards, which poses a perilous threat to humankind and the environment. Rapid urbanization has been increasing the population density in an area, elevating the risk of exposure to technological disasters. Therefore, it is necessary to detect the areas with higher chemical risk to spread awareness about the potential risk zones and reduce actual damage and casualties resulting from the hazardous substance events. The basic design of the study utilizes geospatial analysis to map the TRI (Toxics Release Inventory) facilities in the communities of Texas to establish a relationship between potential </span><span style="font-family:Verdana;">hazardous material release zones and the human population at risk. The</span><span style="font-family:Verdana;"> study identified the vulnerable counties as well as investigated how those risk areas are related to race/ethnicity, income and education. The research would contribute to the policymakers acting on the hazard situation and keep them better prepared for</span><span style="color:red;"> </span><span style="font-family:Verdana;">chemical hazards. In addition, it would help the residents and emergency managers to better understand the circumstance to mitigate the consequences as well as increase their awareness to be ready for the uncertainties in the hotspots involved in high risk of the hazards.
文摘General Aviation Manufacturers Association released the 2023 General Aviation Aircraft Shipments and Billings Report during its annual State of the Industry Press Conference.Overall,when compared to 2022,all aircraft segments saw increases in shipments and preliminary aircraft deliveries were valued at$27.8 billion,an increase of 3.6%.
文摘China's State Council on December 7 released a plan on highlevel institutional opening-up in the Shanghai Free Trade Zone,proposing to build Shanghai into a demonstration area for national institutional opening-up and deepened reforms.
基金Supported by the National Natural Science Foundation of China (60701020)the China Post-Doctoral Science Foundation (20080430988,200801321)the Fundamental Research Funds for the Central Universities (3103001)
文摘As an effective means to actively modify the ionosphere, chemical release can produce artificial ionospheric holes as a consequence of ionization depletion, which can greatly impact on radio wave propagation. In this paper, on the basis of the pre-study results on ionospheric disturbances produced by some representative chemical releases, the radio waves propagation effects of ionospheric holes that are produced by two different release species, water (H2O) and sulfur hexafluoride (SF6), had been investigated and simulated by the three-dimensional (3-D) numerical ray tracing. The results show that 1 the appearance of various artificial ionospheric holes can lead to certain decrease of critical frequency in the ionosphere, and 2 when the wave frequency exceeds the critical frequency, the rays should be multiple reflections or penetrate through the ionospheric hole and focus afterwards with the focus altitude elevated for higher frequencies. This work may provide the necessary theoretical support for chemical release experiments and the evaluation of radio wave propagation effects.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168the National Natural Science Foundation of China,No.31670989the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).
文摘Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
基金supported by Catalan Government,Nos.2014SGR344(to JT),2017SGR704(to JT),2021SGR01214(to MAL)MCIN/AEI/10.13039/501100011033/by“ERDF A way of making Europe,”Nos.SAF2015-67143(to JT),PID2019-106332GB-I00(to JT and MAL)and PID2022-141252NB-I00(to MAL).
文摘During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination(the weakest in acetylcholine release and those that have already become silent).The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development.Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases.