BACKGROUND Bedside needle arthroscopy of the ankle under local anesthesia has been proposed for intra-articular delivery of injectable agents.Accuracy and tolerability of this approach in the clinical setting–includi...BACKGROUND Bedside needle arthroscopy of the ankle under local anesthesia has been proposed for intra-articular delivery of injectable agents.Accuracy and tolerability of this approach in the clinical setting–including patients with end-stage ankle pathology and/or a history of prior surgery–is not known.AIM To assess clinical accuracy and tolerability of bedside needle arthroscopy as a delivery system for injectable agents into the tibiotalar joint.METHODS This was a prospective study that included adult patients who were scheduled for an injection with hyaluronic acid to the tibiotalar joint.In our center,these injections are used as a last resort prior to extensive surgery.The primary outcome was injection accuracy,which was defined as injecting through the arthroscopic cannula with intra-articular positioning confirmed by a clear arthroscopic view of the joint space.Secondary outcome measures included a patientreported numeric rating scale(NRS,0-10)of pain during the procedure and willingness of patients to return for the same procedure.NRS of ankle pain at rest and during walking was collected at baseline and at 2-wk follow-up.Complications were monitored from inclusion up to a 2-wk control visit.RESULTS We performed 24 inspection-injections.Eleven(46%)participants were male,and mean age was 46.8±14.5 years.Osteoarthritis was the indication for injection in 20(83%)cases,of which 8(33%)patients suffered from osteoarthritis Kellgren-Lawrence grade IV,and 10(42%)patients from Kellgren-Lawrence grade III.An osteochondral defect was the indication for injection in 4(17%)cases.A history of ankle surgery was present in 14(58%)participants and a history of multiple ankle surgeries in 11(46%)participants.It was possible to confirm accuracy in 21(88%)procedures.The 3(12%)participants where needle arthroscopy did not reach a clear view of the joint space all suffered from Kellgren-Lawrence grade IV osteoarthritis.Pain during the procedure was reported with a median of 1[interquartile ranges(IQR):0–2].Willingness to return was 100%.Pain in rest decreased from a median NRS of 4(IQR:2–7)at baseline to a median of 3(IQR:1–5)at follow-up(P<0.01).Pain during walking decreased from a median NRS of 8(IQR:6–9)to a median of 7(IQR:4–8)(P<0.01).Infections or other complications were not encountered.CONCLUSION Clinical accuracy and tolerability of bedside needle arthroscopy of the ankle as a delivery system for injectable agents are excellent.Accuracy was 100%in patients without total ventral joint obliteration.展开更多
Intermediate filaments, in addition to microtubules and actin microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that in most cel...Intermediate filaments, in addition to microtubules and actin microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that in most cells, intermediate filament proteins play key roles to reinforce cells subjected to large-deformation, and that they participate in signal transduction, and it was proposed that their nanome- chanical properties are critical to perform those functions. However, it is still poorly understood how the nanoscopic structure, as well as the combination of chemical composition, molecular structure and interfacial properties of these protein molecules contribute to the biomechanical properties of filaments and filament networks. Here we review recent progress in computational and theoretical studies of the intermediate filaments network at various levels in the protein＇s structure. A multiple scale method is discussed, used to couple molecular modeling with atomistic detail to larger-scale material properties of the networked material. It is shown that a finer-trains-coarser method- ology as discussed here provides a useful tool in understanding the biomechanical property and disease mechanism of intermediate filaments, coupling experiment and simulation. It further allows us to improve the understanding of associated disease mechanisms and lays the foundation for engineering the mechanical properties of biomaterials.展开更多
Optimized macroscopic tribological behavior can be anticipated in metallic glasses(MGs)by cryogenic cycling treatment(CCT),which is attributed to enhanced plasticity.However,the intrinsic friction mechanisms of MGs in...Optimized macroscopic tribological behavior can be anticipated in metallic glasses(MGs)by cryogenic cycling treatment(CCT),which is attributed to enhanced plasticity.However,the intrinsic friction mechanisms of MGs induced by cryogenic rejuvenation are still poorly understood.In the present study,nanoscopic wear tests were conducted on the Zr-based MGs surface with different CCT cycles using atomic force microscopy(AFM).After CCT treatment with 100 cycles,the MG displays the highest adhesion and ploughing frictions,but significantly improved anti-wear properties.Adhesion tests and molecular dynamics simulations disclose that the increased adhesion is attributed to the dominance of liquid-like regions in the CCT-treated MGs,and the impact of reduced hardness and weak elastic recovery results in the deteriorated ploughing friction.The enhanced plasticity effectively dissipates the strain from the AFM tip through multiple shear bands and weakens the adhesion during deformation,giving rise to excellent wear resistance.This study elucidates the promoting effect of CCT on the outstanding antiwear performance of MGs,and is helpful for the development of novel alloys.展开更多
The progression of Alzheimer’s disease(AD)is characterized with the deposition and aggregation ofβ-amyloid(Aβ).Visualizing Aβaggregates at high spatial resolution is beneficial for AD diagnosis and treatment.Herei...The progression of Alzheimer’s disease(AD)is characterized with the deposition and aggregation ofβ-amyloid(Aβ).Visualizing Aβaggregates at high spatial resolution is beneficial for AD diagnosis and treatment.Herein,we designed a new molecule by conjugating corannulene(Cor)with rhodamine B isothiocyanate(Rhb),namely Cor-Rhb,for the nanoscopic imaging and modulating Aβpeptide fibrillation.The low duty cycle,high photon output and sufficient switching cycles enable Cor-Rhb suitable for localization-based nanoscopic fluorescence imaging.We find that Cor-Rhb can inhibit Aβpeptides fibrillization and interact directly with mature fibrils,triggering their disaggregation under light illumination.Noticeably reduced Aβ-mediated cytotoxicity after the addition of Cor-Rhb is also confirmed.These explorations suggest that Cor-Rhb displays great potential as a multifunctional therapeutic agent against amyloid-related diseases,and may largely facilitate a variety of super-resolution based biological applications.展开更多
Mitophagy is a complicated process of cell metabolism that exhibits dynamic spatiotemporal coordination between multiple organelles.Despite its relevance to nucleoli,visualizing the distribution of nucleolar RNA in th...Mitophagy is a complicated process of cell metabolism that exhibits dynamic spatiotemporal coordination between multiple organelles.Despite its relevance to nucleoli,visualizing the distribution of nucleolar RNA in the process of mitophagy remains a great challenge because of the difficulty in specifically labeling RNA.展开更多
文摘BACKGROUND Bedside needle arthroscopy of the ankle under local anesthesia has been proposed for intra-articular delivery of injectable agents.Accuracy and tolerability of this approach in the clinical setting–including patients with end-stage ankle pathology and/or a history of prior surgery–is not known.AIM To assess clinical accuracy and tolerability of bedside needle arthroscopy as a delivery system for injectable agents into the tibiotalar joint.METHODS This was a prospective study that included adult patients who were scheduled for an injection with hyaluronic acid to the tibiotalar joint.In our center,these injections are used as a last resort prior to extensive surgery.The primary outcome was injection accuracy,which was defined as injecting through the arthroscopic cannula with intra-articular positioning confirmed by a clear arthroscopic view of the joint space.Secondary outcome measures included a patientreported numeric rating scale(NRS,0-10)of pain during the procedure and willingness of patients to return for the same procedure.NRS of ankle pain at rest and during walking was collected at baseline and at 2-wk follow-up.Complications were monitored from inclusion up to a 2-wk control visit.RESULTS We performed 24 inspection-injections.Eleven(46%)participants were male,and mean age was 46.8±14.5 years.Osteoarthritis was the indication for injection in 20(83%)cases,of which 8(33%)patients suffered from osteoarthritis Kellgren-Lawrence grade IV,and 10(42%)patients from Kellgren-Lawrence grade III.An osteochondral defect was the indication for injection in 4(17%)cases.A history of ankle surgery was present in 14(58%)participants and a history of multiple ankle surgeries in 11(46%)participants.It was possible to confirm accuracy in 21(88%)procedures.The 3(12%)participants where needle arthroscopy did not reach a clear view of the joint space all suffered from Kellgren-Lawrence grade IV osteoarthritis.Pain during the procedure was reported with a median of 1[interquartile ranges(IQR):0–2].Willingness to return was 100%.Pain in rest decreased from a median NRS of 4(IQR:2–7)at baseline to a median of 3(IQR:1–5)at follow-up(P<0.01).Pain during walking decreased from a median NRS of 8(IQR:6–9)to a median of 7(IQR:4–8)(P<0.01).Infections or other complications were not encountered.CONCLUSION Clinical accuracy and tolerability of bedside needle arthroscopy of the ankle as a delivery system for injectable agents are excellent.Accuracy was 100%in patients without total ventral joint obliteration.
文摘Intermediate filaments, in addition to microtubules and actin microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that in most cells, intermediate filament proteins play key roles to reinforce cells subjected to large-deformation, and that they participate in signal transduction, and it was proposed that their nanome- chanical properties are critical to perform those functions. However, it is still poorly understood how the nanoscopic structure, as well as the combination of chemical composition, molecular structure and interfacial properties of these protein molecules contribute to the biomechanical properties of filaments and filament networks. Here we review recent progress in computational and theoretical studies of the intermediate filaments network at various levels in the protein＇s structure. A multiple scale method is discussed, used to couple molecular modeling with atomistic detail to larger-scale material properties of the networked material. It is shown that a finer-trains-coarser method- ology as discussed here provides a useful tool in understanding the biomechanical property and disease mechanism of intermediate filaments, coupling experiment and simulation. It further allows us to improve the understanding of associated disease mechanisms and lays the foundation for engineering the mechanical properties of biomaterials.
基金supported by the National Natural Science Foundation of China(Grant Nos.52175188,and 52201087)the Key Research and Development Program of Shaanxi Province(Grant No.2023-YBGY-434)+3 种基金the Natural Science Foundation of Shaanxi Province(Grant No.2022JM-253)the Open Fund of Liaoning Provincial Key Laboratory of Aero-engine Materials Tribology(Grant No.LKLAMTF202301)the Science and Technology on Reactor System Design Technology Laboratorythe Fundamental Research Funds for the Central Universities。
文摘Optimized macroscopic tribological behavior can be anticipated in metallic glasses(MGs)by cryogenic cycling treatment(CCT),which is attributed to enhanced plasticity.However,the intrinsic friction mechanisms of MGs induced by cryogenic rejuvenation are still poorly understood.In the present study,nanoscopic wear tests were conducted on the Zr-based MGs surface with different CCT cycles using atomic force microscopy(AFM).After CCT treatment with 100 cycles,the MG displays the highest adhesion and ploughing frictions,but significantly improved anti-wear properties.Adhesion tests and molecular dynamics simulations disclose that the increased adhesion is attributed to the dominance of liquid-like regions in the CCT-treated MGs,and the impact of reduced hardness and weak elastic recovery results in the deteriorated ploughing friction.The enhanced plasticity effectively dissipates the strain from the AFM tip through multiple shear bands and weakens the adhesion during deformation,giving rise to excellent wear resistance.This study elucidates the promoting effect of CCT on the outstanding antiwear performance of MGs,and is helpful for the development of novel alloys.
基金This work was supported by the National Natural Science Foundation of China(Nos.22174079 and 21974073).
文摘The progression of Alzheimer’s disease(AD)is characterized with the deposition and aggregation ofβ-amyloid(Aβ).Visualizing Aβaggregates at high spatial resolution is beneficial for AD diagnosis and treatment.Herein,we designed a new molecule by conjugating corannulene(Cor)with rhodamine B isothiocyanate(Rhb),namely Cor-Rhb,for the nanoscopic imaging and modulating Aβpeptide fibrillation.The low duty cycle,high photon output and sufficient switching cycles enable Cor-Rhb suitable for localization-based nanoscopic fluorescence imaging.We find that Cor-Rhb can inhibit Aβpeptides fibrillization and interact directly with mature fibrils,triggering their disaggregation under light illumination.Noticeably reduced Aβ-mediated cytotoxicity after the addition of Cor-Rhb is also confirmed.These explorations suggest that Cor-Rhb displays great potential as a multifunctional therapeutic agent against amyloid-related diseases,and may largely facilitate a variety of super-resolution based biological applications.
基金from the National Natural Science Foundation of China(NSFC,Project No.22174079,21974073).
文摘Mitophagy is a complicated process of cell metabolism that exhibits dynamic spatiotemporal coordination between multiple organelles.Despite its relevance to nucleoli,visualizing the distribution of nucleolar RNA in the process of mitophagy remains a great challenge because of the difficulty in specifically labeling RNA.
