Cryptococcosis,a serious systemic fungal infection caused by Cryptococcus neoformans(C.neoformans)and its variants,poses a significant clinical challenge due to its poor prognosis and severe health implications.The tr...Cryptococcosis,a serious systemic fungal infection caused by Cryptococcus neoformans(C.neoformans)and its variants,poses a significant clinical challenge due to its poor prognosis and severe health implications.The treatment of cryptococcal infections is complicated by several unique factors,stemming from both the pathogenic characteristics of the fungi and the biological barriers they exploit.These include the fungi’s protective capsule,their ability to reside within host macrophages—thereby evading pharmacological intervention—and their involvement in multi-organ infections such as the lung and brain,in particular their strategic positioning within the brain,protected by the blood-brain barrier(BBB).To overcome these obstacles,precise active targeting emerges as a pivotal strategy.Identifying common targets is imperative to enhance therapeutic efficacy while ensuring the druggability of delivery systems.However,research on the methodology for selecting such shared targets remains sparse.In our investigation,we have pioneered the use of secreted proteins as shared target to trace the pathogens and their infection pathways.We identified the mannoprotein Cig1,prominently expressed on the surfaces of infected macrophages,lungs,and brains,as a viable shared target.On this basis,we utilized Hemin,a ligand for Cig1,to design liposomes(Hemin Lip)tailored for addressing complex fungal infections.By leveraging the interaction with the secreted protein Cig1,Hemin Lip specifically identifies and binds to organs and macrophages harboring cryptococcal infections,thereby facilitating targeted and efficacious clearance of both intracellular and extracellular fungus.Moreover,we have extended this targeting mechanism to other nanomedicinal platforms,including albumin nanoparticles.This study proposes an innovative drug delivery model that targets extracellular secretory proteins within the infection microenvironment,offering a streamlined formulation with the potential for effective therapy against complex infections.展开更多
Applications of in-situ and ex-situ spectroscopic ellipsometry （SE） are presented for the development of parametric expressions that define the real and imaginary parts （ε1, ε2） of the complex dielectric functio...Applications of in-situ and ex-situ spectroscopic ellipsometry （SE） are presented for the development of parametric expressions that define the real and imaginary parts （ε1, ε2） of the complex dielectric function spectra of thin film solar cell components. These spectra can then be utilized to analyze the structure of complete thin film solar cells. Optical and structural/compositional models of complete solar cells developed through least squares regression analysis of the SE data acquired for the complete cells enable simulations of external quantum efficiency （EQE） without the need for variable parameters. Such simulations can be compared directly with EQE measurements. From these comparisons, it becomes possible to understand in detail the origins of optical and electronic gains and losses in thin film photovoltaics （PC） technologies and, as a result, the underlying performance limitations. In fact, optical losses that occur when above-bandgap photons are not absorbed in the active layers can be distinguished from electronic losses when electron-hole pairs generated in the active layers are not collected. This overall methodology has been applied to copper indium-gallium diselenide （Culn1-xGaxSe2; CIGS） solar cells, a key commercialized thin film PV technology. CIGS solar cells with both standard thickness （〉2 μm） and thin （〈1 μm） absorber layers are studied by applying SE to obtain inputs for EQE simulations and enabling comparisons of simulated and measured EQE spectra. SE data analysis is challenging for CIGS material components and solar cells because of the need to develop an appropriate （ε1, ε2） database for the CIGS alloys and to extract absorber layer Ga profiles for accurate structural/compositional models. For cells with standard thickness absorbers, excellent agreement is found between the simulated and measured EQE, the latter under the assumption of 100% collection from the active layers, which include the CIGS bulk and CIGS/CdS heterojunction interface layers. For cells with thin absorbers, however, an observed difference between the simulated and measured EQE can be attributed to losses via carrier recombination within a- 0.15 μm thickness of CIGS adjacent to the Mo back contact. By introducing a carrier collection probability profile into the simulation, much closer agreement is obtained between the simulated and measured EQE. In addition to the single spot capability demonstrated in this study, ex-situ SE can be applied as well to generate high resolution maps of thin film multilayer structure, component layer properties and their profiles, as well as short-circuit current density predictions. Such mapping is possible due to the high measurement speed of 〈1 s per （ , 4） spectra achievable by the multichannel ellipsometer.展开更多
基金supported by the National Natural Science Foundation of China(NSFC No.82073789)Chongqing’Special Funding for Postdoctoral Research Projects(2212013362060154)+1 种基金the Fundamental Research Funds for the Central Universities(SWU120068)the Venture and Innovation Support Program for Chongqing Over-seas Returnees(cx2022025)。
文摘Cryptococcosis,a serious systemic fungal infection caused by Cryptococcus neoformans(C.neoformans)and its variants,poses a significant clinical challenge due to its poor prognosis and severe health implications.The treatment of cryptococcal infections is complicated by several unique factors,stemming from both the pathogenic characteristics of the fungi and the biological barriers they exploit.These include the fungi’s protective capsule,their ability to reside within host macrophages—thereby evading pharmacological intervention—and their involvement in multi-organ infections such as the lung and brain,in particular their strategic positioning within the brain,protected by the blood-brain barrier(BBB).To overcome these obstacles,precise active targeting emerges as a pivotal strategy.Identifying common targets is imperative to enhance therapeutic efficacy while ensuring the druggability of delivery systems.However,research on the methodology for selecting such shared targets remains sparse.In our investigation,we have pioneered the use of secreted proteins as shared target to trace the pathogens and their infection pathways.We identified the mannoprotein Cig1,prominently expressed on the surfaces of infected macrophages,lungs,and brains,as a viable shared target.On this basis,we utilized Hemin,a ligand for Cig1,to design liposomes(Hemin Lip)tailored for addressing complex fungal infections.By leveraging the interaction with the secreted protein Cig1,Hemin Lip specifically identifies and binds to organs and macrophages harboring cryptococcal infections,thereby facilitating targeted and efficacious clearance of both intracellular and extracellular fungus.Moreover,we have extended this targeting mechanism to other nanomedicinal platforms,including albumin nanoparticles.This study proposes an innovative drug delivery model that targets extracellular secretory proteins within the infection microenvironment,offering a streamlined formulation with the potential for effective therapy against complex infections.
基金supported by the Department of Energy and the National Science Foundation(NSF)under the F-PACE Program,Award Number DE-EE0005400supported by NSF Award EECS-1665172
文摘Applications of in-situ and ex-situ spectroscopic ellipsometry （SE） are presented for the development of parametric expressions that define the real and imaginary parts （ε1, ε2） of the complex dielectric function spectra of thin film solar cell components. These spectra can then be utilized to analyze the structure of complete thin film solar cells. Optical and structural/compositional models of complete solar cells developed through least squares regression analysis of the SE data acquired for the complete cells enable simulations of external quantum efficiency （EQE） without the need for variable parameters. Such simulations can be compared directly with EQE measurements. From these comparisons, it becomes possible to understand in detail the origins of optical and electronic gains and losses in thin film photovoltaics （PC） technologies and, as a result, the underlying performance limitations. In fact, optical losses that occur when above-bandgap photons are not absorbed in the active layers can be distinguished from electronic losses when electron-hole pairs generated in the active layers are not collected. This overall methodology has been applied to copper indium-gallium diselenide （Culn1-xGaxSe2; CIGS） solar cells, a key commercialized thin film PV technology. CIGS solar cells with both standard thickness （〉2 μm） and thin （〈1 μm） absorber layers are studied by applying SE to obtain inputs for EQE simulations and enabling comparisons of simulated and measured EQE spectra. SE data analysis is challenging for CIGS material components and solar cells because of the need to develop an appropriate （ε1, ε2） database for the CIGS alloys and to extract absorber layer Ga profiles for accurate structural/compositional models. For cells with standard thickness absorbers, excellent agreement is found between the simulated and measured EQE, the latter under the assumption of 100% collection from the active layers, which include the CIGS bulk and CIGS/CdS heterojunction interface layers. For cells with thin absorbers, however, an observed difference between the simulated and measured EQE can be attributed to losses via carrier recombination within a- 0.15 μm thickness of CIGS adjacent to the Mo back contact. By introducing a carrier collection probability profile into the simulation, much closer agreement is obtained between the simulated and measured EQE. In addition to the single spot capability demonstrated in this study, ex-situ SE can be applied as well to generate high resolution maps of thin film multilayer structure, component layer properties and their profiles, as well as short-circuit current density predictions. Such mapping is possible due to the high measurement speed of 〈1 s per （ , 4） spectra achievable by the multichannel ellipsometer.
