Extracellular vesicles(EVs)have been identified as promising biomarkers for the noninvasive diagnosis of various diseases.However,challenges in separating EVs from soluble proteins have resulted in variable EV recover...Extracellular vesicles(EVs)have been identified as promising biomarkers for the noninvasive diagnosis of various diseases.However,challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low purities.Here,we report a high-yield(>90%)and rapid(<10 min)EV isolation method called FLocculation via Orbital Acoustic Trapping(FLOAT).The FLOAT approach utilizes an acoustofluidic droplet centrifuge to rotate and controllably heat liquid droplets.By adding a thermoresponsive polymer flocculant,nanoparticles as small as 20 nm can be rapidly and selectively concentrated at the center of the droplet.We demonstrate the ability of FLOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein,addressing a significant obstacle in the development of EV-based liquid biopsies.Due to its high-yield nature,FLOAT reduces biofluid starting volume requirements by a factor of 100(from 20 mL to 200µL),demonstrating its promising potential in point-of-care diagnostics.展开更多
With the rapid development of space science projects,large deployable mechanisms have been widely used.However,due to the effects of mechanical friction and gravitational acceleration,on-orbit mechanisms cannot be alw...With the rapid development of space science projects,large deployable mechanisms have been widely used.However,due to the effects of mechanical friction and gravitational acceleration,on-orbit mechanisms cannot be always deployed to the expected pose.For some precision optical mechanisms,even a minor deviation can result in significant error,so it needs to be measured and corrected.In this paper,the deployment process was modeled and simplified as rotation under single-rotation-axis constraint and translation under single-direction constraint.To solve the problem,a method based on cross-ratio invariability was proposed.The proposed method does not rely on camera calibration techniques,as well as artificial marking points,both of which are necessary in PnP.Instead,only three calibration images before launch and a measurement image on orbit were required.Simulations and experiments demonstrated that the proposed method is more accurate than PnP.In addition,experiments also proved that the feasibility of the proposed method under dark conditions with the aid of a light source and some reflective marking points.展开更多
Nanocarrier and exosome encapsulation has been found to significantly increase the efficacy of targeted drug delivery while also minimizing unwanted side effects.However,the development of exosome-encapsulated drug na...Nanocarrier and exosome encapsulation has been found to significantly increase the efficacy of targeted drug delivery while also minimizing unwanted side effects.However,the development of exosome-encapsulated drug nanocarriers is limited by low drug loading efficiencies and/or complex,time-consuming drug loading processes.Herein,we have developed an acoustofluidic device that simultaneously performs both drug loading and exosome encapsulation.By synergistically leveraging the acoustic radiation force,acoustic microstreaming,and shear stresses in a rotating droplet,the concentration,and fusion of exosomes,drugs,and porous silica nanoparticles is achieved.The final product consists of drug-loaded silica nanocarriers that are encased within an exosomal membrane.The drug loading efficiency is significantly improved,with nearly 30%of the free drug(e.g.,doxorubicin)molecules loaded into the nanocarriers.Furthermore,this acoustofluidic drug loading system circumvents the need for complex chemical modification,allowing drug loading and encapsulation to be completed within a matter of minutes.These exosome-encapsulated nanocarriers exhibit excellent efficiency in intracellular transport and are capable of significantly inhibiting tumor cell proliferation.By utilizing physical forces to rapidly generate hybrid nanocarriers,this acoustofluidic drug loading platform wields the potential to significantly impact innovation in both drug delivery research and applications.展开更多
Inflammatory leukocytes infiltration is orchestrated by mechanisms involving chemokines,selectins,addressins and other adhesion molecules derived from endothelial cells(ECs),but how they respond to inflammatory cues a...Inflammatory leukocytes infiltration is orchestrated by mechanisms involving chemokines,selectins,addressins and other adhesion molecules derived from endothelial cells(ECs),but how they respond to inflammatory cues and coordinate leukocyte transmigration remain elusive.In this study,using hepatic ischemia/reperfusion injury(HIRI)as a model,we identified that endothelial Notch activation was rapidly and dynamically induced in liver sinusoidal endothelial cells(LSECs)in acute inflammation.In mice with EC-specific Notch activation(NICeCA),HIRI induced exacerbated liver damage.Consistently,endothelial Notch activation enhanced neutrophil infiltration and tumor necrosis factor(TNF)-αexpression in HIRI.Transcriptome analysis and further qRT-PCR as well as immunofluorescence indicated that endomucin(EMCN),a negative regulator of leukocyte adhesion,was downregulated in LSECs from NICeCA mice.EMCN was downregulated during HIRI in wild-type mice and in vitro cultured ECs insulted by hypoxia/re-oxygenation injury.Notch activation in ECs led to increased neutrophil adhesion and transendothelial migration,which was abrogated by EMCN overexpression in vitro.In mice deficient of RBPj,the integrative transcription factor of canonical Notch signaling,although overwhelming sinusoidal malformation aggravated HIRI,the expression of EMCN was upregulated;and pharmaceutical Notch blockade in vitro also upregulated EMCN and inhibited transendothelial migration of neutrophils.The Notch activation-exaggerated HIRI was compromised by blocking LFA-1,which mediated leukocyte adherence by associating with EMCN.Therefore,endothelial Notch signaling controls neutrophil transmigration via EMCN to modulate acute inflammation in HIRI.展开更多
We report the discovery of a new noncentrosymmetric superconductor CaPtAs.It crystallizes in a tetragonal structure(space group I41md,No.109),featuring three dimensional honeycomb networks of Pt-As and a much elongate...We report the discovery of a new noncentrosymmetric superconductor CaPtAs.It crystallizes in a tetragonal structure(space group I41md,No.109),featuring three dimensional honeycomb networks of Pt-As and a much elongated c-axis(a=b=4.18?,and c=43.70?).The superconductivity of CaPtAs with Tc=1.47 K was characterized by means of electrical resistivity,specific heat,and ac magnetic susceptibility.The electronic specific heat Ce(T)/T shows evidence for a deviation from the behavior of a conventional BCS superconductor,and can be reasonably fitted by a p-wave model.The upper critical fieldμ0Hc2 of CaPtAs exhibits a moderate anisotropy,with an in-plane value of around 204 mT and an out-of-plane value of 148 mT.Density functional theory calculations indicate that the Pt-5 d and As-4 p orbitals mainly contribute to the density of states near the Fermi level,showing that the Pt-As honeycomb networks may significantly influence the superconducting properties.展开更多
基金supported by the National Institutes of Health(R01HD103727,UH3TR002978,U18TR003778,R01GM141055,R01GM132603,R01GM145960,R01GM144417,and R01GM135486)the National Science Foundation(CMMI-2104295)the National Science Foundation Graduate Research Fellowship(2139754).
文摘Extracellular vesicles(EVs)have been identified as promising biomarkers for the noninvasive diagnosis of various diseases.However,challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low purities.Here,we report a high-yield(>90%)and rapid(<10 min)EV isolation method called FLocculation via Orbital Acoustic Trapping(FLOAT).The FLOAT approach utilizes an acoustofluidic droplet centrifuge to rotate and controllably heat liquid droplets.By adding a thermoresponsive polymer flocculant,nanoparticles as small as 20 nm can be rapidly and selectively concentrated at the center of the droplet.We demonstrate the ability of FLOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein,addressing a significant obstacle in the development of EV-based liquid biopsies.Due to its high-yield nature,FLOAT reduces biofluid starting volume requirements by a factor of 100(from 20 mL to 200µL),demonstrating its promising potential in point-of-care diagnostics.
基金Supported in part by the National Natural Science Foundation of China(No.62271148).
文摘With the rapid development of space science projects,large deployable mechanisms have been widely used.However,due to the effects of mechanical friction and gravitational acceleration,on-orbit mechanisms cannot be always deployed to the expected pose.For some precision optical mechanisms,even a minor deviation can result in significant error,so it needs to be measured and corrected.In this paper,the deployment process was modeled and simplified as rotation under single-rotation-axis constraint and translation under single-direction constraint.To solve the problem,a method based on cross-ratio invariability was proposed.The proposed method does not rely on camera calibration techniques,as well as artificial marking points,both of which are necessary in PnP.Instead,only three calibration images before launch and a measurement image on orbit were required.Simulations and experiments demonstrated that the proposed method is more accurate than PnP.In addition,experiments also proved that the feasibility of the proposed method under dark conditions with the aid of a light source and some reflective marking points.
基金support from the National Institutes of Health(Grant Nos.R01HD103727,UH3TR002978,U18TR003778,R01GM132603,R01GM143439,R01GM135486,R21HD102790,R44HL140800,and R44AG063543)the National Science Foundation(Grant Nos.ECCS-1807601 and CMM1-2104295)supported by the National Science Foundation Graduate Research Fellowship under Grant No.1644868.
文摘Nanocarrier and exosome encapsulation has been found to significantly increase the efficacy of targeted drug delivery while also minimizing unwanted side effects.However,the development of exosome-encapsulated drug nanocarriers is limited by low drug loading efficiencies and/or complex,time-consuming drug loading processes.Herein,we have developed an acoustofluidic device that simultaneously performs both drug loading and exosome encapsulation.By synergistically leveraging the acoustic radiation force,acoustic microstreaming,and shear stresses in a rotating droplet,the concentration,and fusion of exosomes,drugs,and porous silica nanoparticles is achieved.The final product consists of drug-loaded silica nanocarriers that are encased within an exosomal membrane.The drug loading efficiency is significantly improved,with nearly 30%of the free drug(e.g.,doxorubicin)molecules loaded into the nanocarriers.Furthermore,this acoustofluidic drug loading system circumvents the need for complex chemical modification,allowing drug loading and encapsulation to be completed within a matter of minutes.These exosome-encapsulated nanocarriers exhibit excellent efficiency in intracellular transport and are capable of significantly inhibiting tumor cell proliferation.By utilizing physical forces to rapidly generate hybrid nanocarriers,this acoustofluidic drug loading platform wields the potential to significantly impact innovation in both drug delivery research and applications.
基金This work was supported by grants from the National Natural Science Foundation of China(31730041,31671523,and 81470416).
文摘Inflammatory leukocytes infiltration is orchestrated by mechanisms involving chemokines,selectins,addressins and other adhesion molecules derived from endothelial cells(ECs),but how they respond to inflammatory cues and coordinate leukocyte transmigration remain elusive.In this study,using hepatic ischemia/reperfusion injury(HIRI)as a model,we identified that endothelial Notch activation was rapidly and dynamically induced in liver sinusoidal endothelial cells(LSECs)in acute inflammation.In mice with EC-specific Notch activation(NICeCA),HIRI induced exacerbated liver damage.Consistently,endothelial Notch activation enhanced neutrophil infiltration and tumor necrosis factor(TNF)-αexpression in HIRI.Transcriptome analysis and further qRT-PCR as well as immunofluorescence indicated that endomucin(EMCN),a negative regulator of leukocyte adhesion,was downregulated in LSECs from NICeCA mice.EMCN was downregulated during HIRI in wild-type mice and in vitro cultured ECs insulted by hypoxia/re-oxygenation injury.Notch activation in ECs led to increased neutrophil adhesion and transendothelial migration,which was abrogated by EMCN overexpression in vitro.In mice deficient of RBPj,the integrative transcription factor of canonical Notch signaling,although overwhelming sinusoidal malformation aggravated HIRI,the expression of EMCN was upregulated;and pharmaceutical Notch blockade in vitro also upregulated EMCN and inhibited transendothelial migration of neutrophils.The Notch activation-exaggerated HIRI was compromised by blocking LFA-1,which mediated leukocyte adherence by associating with EMCN.Therefore,endothelial Notch signaling controls neutrophil transmigration via EMCN to modulate acute inflammation in HIRI.
基金the National Key R&D Program of China(Grant Nos.2016YFA0300202,and 2017YFA0303100)the National Natural Science Foundation of China(Grant Nos.U1632275,and 11874320)+1 种基金the Science Challenge Project of China(Grant No.TZ2016004)the Fundamental Research Funds for the Central Universities.
文摘We report the discovery of a new noncentrosymmetric superconductor CaPtAs.It crystallizes in a tetragonal structure(space group I41md,No.109),featuring three dimensional honeycomb networks of Pt-As and a much elongated c-axis(a=b=4.18?,and c=43.70?).The superconductivity of CaPtAs with Tc=1.47 K was characterized by means of electrical resistivity,specific heat,and ac magnetic susceptibility.The electronic specific heat Ce(T)/T shows evidence for a deviation from the behavior of a conventional BCS superconductor,and can be reasonably fitted by a p-wave model.The upper critical fieldμ0Hc2 of CaPtAs exhibits a moderate anisotropy,with an in-plane value of around 204 mT and an out-of-plane value of 148 mT.Density functional theory calculations indicate that the Pt-5 d and As-4 p orbitals mainly contribute to the density of states near the Fermi level,showing that the Pt-As honeycomb networks may significantly influence the superconducting properties.