2D nanomaterials have attracted broad interest in the field of biomedicine owing to their large surface area, high drug‐loading capacity, and excellent photothermal conversion. However, few studies ...report their “enzyme‐like” catalytic performance because it is difficult to prepare enzymatic nanosheets with small size and ultrathin thickness by current synthetic protocols. Herein, a novel one‐step wet‐chemical method is first proposed for protein‐directed synthesis of 2D MnO2 nanosheets (M‐NSs), in which the size and thickness can be easily adjusted by the protein dosage. Then, a unique sono‐chemical approach is introduced for surface functionalization of the M‐NSs with high dispersity/stability as well as metal‐cation‐chelating capacity, which can not only chelate 64Cu radionuclides for positron emission tomography (PET) imaging, but also capture the potentially released Mn2+ for enhanced biosafety. Interestingly, the resulting M‐NS exhibits excellent enzyme‐like activity to catalyze the oxidation of glucose, which represents an alternative paradigm of acute glucose oxidase for starving cancer cells and sensitizing them to thermal ablation. Featured with outstanding phototheranostic performance, the well‐designed M‐NS can achieve effective photoacoustic‐imaging‐guided synergistic starvation‐enhanced photothermal therapy. This study is expected to establish a new enzymatic phototheranostic paradigm based on small‐sized and ultrathin M‐NSs, which will broaden the application of 2D nanomaterials.
A 2D enzymatic MnO2 nanosheet, M‐NS, is developed by a novel one‐step wet‐chemical synthesis and followed by a unique sono‐chemical modification. The M‐NS, with a small and ultrathin morphology, exhibits intriguing glucose‐oxidase‐like catalytic activity and excellent phototheranostic performance. An effective photoacoustic‐imaging‐guided synergistic starvation‐enhanced photothermal therapy is successfully achieved, broadening the application of 2D nanomaterials in biomedicine.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
2D nanomaterials have attracted broad interest in the field of biomedicine owing to their large surface area, high drug-loading capacity, and excellent photothermal conversion. However, few studies ...report their "enzyme-like" catalytic performance because it is difficult to prepare enzymatic nanosheets with small size and ultrathin thickness by current synthetic protocols. Herein, a novel one-step wet-chemical method is first proposed for protein-directed synthesis of 2D MnO
nanosheets (M-NSs), in which the size and thickness can be easily adjusted by the protein dosage. Then, a unique sono-chemical approach is introduced for surface functionalization of the M-NSs with high dispersity/stability as well as metal-cation-chelating capacity, which can not only chelate
Cu radionuclides for positron emission tomography (PET) imaging, but also capture the potentially released Mn
for enhanced biosafety. Interestingly, the resulting M-NS exhibits excellent enzyme-like activity to catalyze the oxidation of glucose, which represents an alternative paradigm of acute glucose oxidase for starving cancer cells and sensitizing them to thermal ablation. Featured with outstanding phototheranostic performance, the well-designed M-NS can achieve effective photoacoustic-imaging-guided synergistic starvation-enhanced photothermal therapy. This study is expected to establish a new enzymatic phototheranostic paradigm based on small-sized and ultrathin M-NSs, which will broaden the application of 2D nanomaterials.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The maintenance of uric acid levels is crucial for the human body. In this study, the feasibility of using portable ultraviolet (UV) spectrophotometry to measure the uric acid of spot urine without ...the need to add reagents has been demonstrated for the first time. UV spectral analysis has been used to inspect the uric acid concentration in urine. It is found that the absorption spectrum of urine has a high correlation with the concentration of uric acid at a wavelength of around 290-300 nm. Uric acid levels measured with a spectral analyzer compared to uric acid concentrations measured with a traditional biochemical analysis showed good agreement. The portable prototype is label-free and capable of displaying the inspection result of each measurement within 10 s. In the long run, this device can assist people in checking uric acid levels of spot urine with higher frequency and can adjust diet or medication in real time for more efficient health management.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
4.
Emerging Roles of Air Gases in Lipid Bilayers Lee, Chia‐Wei; Chiang, Ya‐Ling; Liu, Ji‐Ting ...
Small (Weinheim an der Bergstrasse, Germany),
10/2018, Volume:
14, Issue:
40
Journal Article
Peer reviewed
Recent studies indicate that changing the physical properties of lipid bilayers may profoundly change the function of membrane proteins. Here, the effects of dissolved nitrogen and oxygen molecules ...on the mechanical properties and stability of lipid bilayers are investigated using differential confocal microscopy, atomic force microscopy, and molecular dynamics simulations. All experiments evidence the presence of dissolved air gas in lipid bilayers prepared without gas control. The lipid bilayers in degassed solutions are softer and less stable than those in ambient solutions. High concentrations of nitrogen increase the bending moduli and stability of the lipid bilayers and impede phase separation in ternary lipid bilayers. The effect of oxygen is less prominent. Molecular dynamics simulations indicate that higher nitrogen affinity accounts for increased rigidity. These findings have fundamental and wide implications for phenomena related to lipid bilayers and cell membranes, including the origin of life.
Air gas molecules are found to play essential roles in determining the mechanical properties and dynamics of lipid membranes by using molecular dynamics simulations, differential confocal microscopy, and atomic force microscopy. The lipid bilayers in degassed solutions are softer and less stable than those in ambient solutions. High concentrations of nitrogen increase the membrane bending moduli and stability.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Amyloid fibrils play a crucial role in many human diseases and are found to function in a range of physiological processes from bacteria to human. They have also been gaining importance in ...nanotechnology applications. Understanding the mechanisms behind amyloid formation can help develop strategies towards the prevention of fibrillation processes or create new technological applications. It is thus essential to observe the structures of amyloids and their self-assembly processes at the nanometer-scale resolution under physiological conditions. In this work, we used highly force-sensitive frequency-modulation atomic force microscopy (FM-AFM) to characterize the fibril structures formed by the N-terminal domain of a bacterial division protein MinE in solution. The approach enables us to investigate the fibril morphology and protofibril organization over time progression and in response to changes in ionic strength, molecular crowding, and upon association with different substrate surfaces. In addition to comparison of the fibril structure and behavior of MinE1-31 under varying conditions, the study also broadens our understanding of the versatile behavior of amyloid-substrate surface interactions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The pole-to-pole oscillation of the Min proteins in Escherichia coli results in the inhibition of aberrant polar division, thus facilitating placement of the division septum at the midcell. MinE of ...the Min system forms a ring-like structure that plays a critical role in triggering the oscillation cycle. However, the mechanism underlying the formation of the MinE ring remains unclear. This study demonstrates that MinE self-assembles into fibrillar structures on the supported lipid bilayer. The MinD-interacting domain of MinE shows amyloidogenic properties, providing a possible mechanism for self-assembly of MinE. Supporting the idea, mutations in residues Ile-24 and Ile-25 of the MinD-interacting domain affect fibril formation, membrane binding ability of MinE and MinD, and subcellular localization of three Min proteins. Additional mutations in residues Ile-72 and Ile-74 suggest a role of the C-terminal domain of MinE in regulating the folding propensity of the MinD-interacting domain for different molecular interactions. The study suggests a self-assembly mechanism that may underlie the ring-like structure formed by MinE-GFP observed in vivo.
Background: MinE of the Min system forms a ring-like structure that plays a critical role in triggering the oscillation cycle.
Results: MinE self-assembles into fibrillar structures on the membrane through the N-terminal domain.
Conclusion: A self-assembly mechanism may underlie the formation of the MinE ring.
Significance: This study suggests that self-assembly of MinE on the membrane is a fundamental property of the Min system.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hexanucleotide expansions, GGGGCC, in the non-coding regions of the C9orf72 gene were found in major frontotemporal lobar dementia and amyotrophic lateral sclerosis patients (C9FTD/ALS). In addition ...to possible RNA toxicity, several dipeptide repeats (DPRs) are translated through repeat-associated non-ATG-initiated translation. The DPRs, including poly(GA), poly(GR), poly(GP), poly(PR), and poly(PA), were found in the brains and spinal cords of C9FTD/ALS patients. Among the DPRs, poly(GA) is highly susceptible to form cytoplasmic inclusions, which is a characteristic of C9FTD/ALS. To elucidate DPR aggregation, we used synthetic (GA)15 DPR as a model system to examine the aggregation and structural properties in vitro. We found that (GA)15 with 15 repeats fibrillates rapidly and ultimately forms flat, ribbon-type fibrils evidenced by transmission electron microscopy and atomic force microscopy. The fibrils are capable of amyloid dye binding and contain a characteristic cross-β sheet structure, as revealed by x-ray scattering. Furthermore, using neuroblastoma cells, we demonstrated the neurotoxicity and cell-to-cell transmission property of (GA)15 DPR. Overall, our results show the structural and toxicity properties of GA DPR to facilitate future DPR-related therapeutic development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The onset or progression of numerous neurodegenerative diseases occurs due to aggregation of proteins that ultimately form fibrils. The assembly and morphology of fibrils are susceptible to ...environmental factors. In this work, we used atomic force microscopy (AFM) to investigate the effects of dissolved nitrogen and oxygen molecules on the morphology of fibrils formed by a hydrophobic amyloid peptide implicated in amyotrophic lateral sclerosis, 15 repeats of glycine-alanine, on a highly oriented pyrolytic graphite substrate. We started with preformed fibril solutions that were then diluted with buffers of different gas conditions, resulting in the aggregation of the fibrils into different morphologies that were revealed by AFM after adsorption on the substrate. Straight fibrils were observed in both degassed and ambient buffers, but a stronger lateral association was seen in degassed buffers. Smaller and softer fibrils were observed in O
-supersaturated buffers, and plaque-like fibril aggregates of considerably large size were evident in N
-supersaturated buffers. In overnight incubation experiments, we observed changes in both the morphology and height of the fibril aggregates, and their evolution varied with different gas conditions. These findings indicate that the gas type and concentration affect the aggregation of amyloid fibrils and may facilitate the development of biomaterial applications and treatments for amyloid-related diseases.
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IJS, KILJ, NUK, PNG, UL, UM
Utilizing the ultra sensitivity of surface plasmon resonance (SPR) biosensor to examine drug resistance of bacteria was studied in this research. Susceptible and resistant strains of Escherichia coli ...JM109 to ampicillin and those of Staphylococcus epidermidis to tetracycline, served as a blind test, were examined. The bacteria adhered on the Au thin film was treated by the injection of antibiotic flow. The optical property change of the bacteria responded to antibiotics were recorded through SPR mechanism. As a result, the susceptible strain of E. coli generally revealed more than three times of SPR angle shift when compared to the resistant one; the susceptible strain of S. epidermidis revealed irregular SPR angle shift while the resistant strain kept the SPR angle almost unchanged. The new SPR method took less than 2h of antibiotic treatment time to complete the antimicrobial susceptibility test. Different from conventional applications of SPR, specific antibodies is not required in this method. As compared to the conventional assays, Kirby-Bauer disk diffusion and variations of broth microdilution usually take 1 day to weeks to issue the report. Using this SPR assay can greatly reduce the waiting period for laboratory tests, and can therefore benefit patients who need proper antibiotic treatments to control bacterial infections. The sensitivity of the SPR biosensor built for the application is around 1.4×10−4 on the refractive index.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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