Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understan...Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.展开更多
1.Introduction.The Ti6Al4V alloy is extensively utilized across various indus-trial sectors due to its favorable characteristics,such as lightweight design,high strength,and resistance to corrosion[1].In effort s to f...1.Introduction.The Ti6Al4V alloy is extensively utilized across various indus-trial sectors due to its favorable characteristics,such as lightweight design,high strength,and resistance to corrosion[1].In effort s to further reduce weight,functional elements like electric actuators can be substituted with intelligent materials like shape memory alloys(SMAs)[2,3].Among SMAs,NiTi alloy stands out for its sens-ing and actuation capabilities,significantly enhancing the safety and reliability of engineering structures[4,5].Integrating Ti6Al4V and NiTi alloys within a single component holds the potential to provide precise feedback on mechanical,thermal,or environmen-tal conditions[6,7].展开更多
The lamellar layer of intermetallic compounds(IMCs)was adversely affected the performance of welding-brazing joints in Al/steel dissimilar metals.In this study,a short fiber-like surface morphology was fabricated on t...The lamellar layer of intermetallic compounds(IMCs)was adversely affected the performance of welding-brazing joints in Al/steel dissimilar metals.In this study,a short fiber-like surface morphology was fabricated on the butt surface of Q235 steel via laser.The interaction behavior between the short fibers and the molten pool was captured using a high-speed camera.Laser-arc hybrid welding-brazing was then employed to join Al(6061-T6)to the steel.This process successfully created a short fiber-like interface structure at the joint.The relationship between microstructure and mechanical properties was investigated,compared with Al/bare steel(ABS)joint.The research results indicated that the IMCs layer consisted of FeAl_(3)and Fe_(2)Al_(5).The interface strength of the Al/short fiber-like surface structural steel(ASFSSS)joint reached 153.2 MPa,an 82.2%increase compared to the ABS joint,which reached 84.1 MPa.When the ASFSSS joints without the reinforcement were bent to 58.2°and 25.2°in the longitudinal and transverse direction,respectively,they remained intact.However,cracks were discovered when the bending angle of the ABS reached 39.1°and 0°in the two directions.Numerical simulation revealed that the short fiber-like interface structure significantly reduced residual stress and improved the stress distribution in the weld,thereby enhancing the strength and toughness of Al/steel dissimilar joints.The crack propagation path in the ASFSSS joint was deflected into the weld when it encountered short fibers,and the fracture morphology presented the characteristic of ductile-brittle mixed fracture.展开更多
基金funded by NIH-NIA R01AG061708 (to PHO)Patrick Grange Memorial Foundation (to PHO)+1 种基金A Long Swim (to PHO)CureSPG4 Foundation (to PHO)。
文摘Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.
基金supported by the National Natural Science Foundation of China(Grant No.52235006)the National Key Research and Development Program of China(Grant No.2022YFB4600500)+3 种基金the National Natural Science Foundation of China(Grant Nos.52025053 and 52105303)the Natural Science Foundation of Jilin Province(Grant No.20220101209JC)the Postdoctoral Fellow-ship Program of CPSF(Grant GZC20240587 and GZC20230944)the Graduate Innovation Fund of Jilin University(2024CX063).
文摘1.Introduction.The Ti6Al4V alloy is extensively utilized across various indus-trial sectors due to its favorable characteristics,such as lightweight design,high strength,and resistance to corrosion[1].In effort s to further reduce weight,functional elements like electric actuators can be substituted with intelligent materials like shape memory alloys(SMAs)[2,3].Among SMAs,NiTi alloy stands out for its sens-ing and actuation capabilities,significantly enhancing the safety and reliability of engineering structures[4,5].Integrating Ti6Al4V and NiTi alloys within a single component holds the potential to provide precise feedback on mechanical,thermal,or environmen-tal conditions[6,7].
基金supported by the National Natural Science Foundation of China(No.52275306)the Beijing Municipal Natural Science Foundation(No.3232021).
文摘The lamellar layer of intermetallic compounds(IMCs)was adversely affected the performance of welding-brazing joints in Al/steel dissimilar metals.In this study,a short fiber-like surface morphology was fabricated on the butt surface of Q235 steel via laser.The interaction behavior between the short fibers and the molten pool was captured using a high-speed camera.Laser-arc hybrid welding-brazing was then employed to join Al(6061-T6)to the steel.This process successfully created a short fiber-like interface structure at the joint.The relationship between microstructure and mechanical properties was investigated,compared with Al/bare steel(ABS)joint.The research results indicated that the IMCs layer consisted of FeAl_(3)and Fe_(2)Al_(5).The interface strength of the Al/short fiber-like surface structural steel(ASFSSS)joint reached 153.2 MPa,an 82.2%increase compared to the ABS joint,which reached 84.1 MPa.When the ASFSSS joints without the reinforcement were bent to 58.2°and 25.2°in the longitudinal and transverse direction,respectively,they remained intact.However,cracks were discovered when the bending angle of the ABS reached 39.1°and 0°in the two directions.Numerical simulation revealed that the short fiber-like interface structure significantly reduced residual stress and improved the stress distribution in the weld,thereby enhancing the strength and toughness of Al/steel dissimilar joints.The crack propagation path in the ASFSSS joint was deflected into the weld when it encountered short fibers,and the fracture morphology presented the characteristic of ductile-brittle mixed fracture.
