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1.
ChemistryOpen ; 13(7): e202300263, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38426687

RESUMO

Organophosphates (OPs) are a class of neurotoxic acetylcholinesterase inhibitors including widely used pesticides as well as nerve agents such as VX and VR. Current treatment of these toxins relies on reactivating acetylcholinesterase, which remains ineffective. Enzymatic scavengers are of interest for their ability to degrade OPs systemically before they reach their target. Here we describe a library of computationally designed variants of phosphotriesterase (PTE), an enzyme that is known to break down OPs. The mutations G208D, F104A, K77A, A80V, H254G, and I274N broadly improve catalytic efficiency of VX and VR hydrolysis without impacting the structure of the enzyme. The mutation I106 A improves catalysis of VR and L271E abolishes activity, likely due to disruptions of PTE's structure. This study elucidates the importance of these residues and contributes to the design of enzymatic OP scavengers with improved efficiency.


Assuntos
Hidrolases de Triester Fosfórico , Hidrolases de Triester Fosfórico/metabolismo , Hidrolases de Triester Fosfórico/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Compostos Organotiofosforados/química , Compostos Organotiofosforados/metabolismo , Mutação , Hidrólise , Modelos Moleculares
2.
Small ; : e2307750, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38431939

RESUMO

As an innovative technology, four-dimentional (4D) printing is built upon the principles of three-dimentional (3D) printing with an additional dimension: time. While traditional 3D printing creates static objects, 4D printing generates "responsive 3D printed structures", enabling them to transform or self-assemble in response to external stimuli. Due to the dynamic nature, 4D printing has demonstrated tremendous potential in a range of industries, encompassing aerospace, healthcare, and intelligent devices. Nanotechnology has gained considerable attention owing to the exceptional properties and functions of nanomaterials. Incorporating nanomaterials into an intelligent matrix enhances the physiochemical properties of 4D printed constructs, introducing novel functions. This review provides a comprehensive overview of current applications of nanomaterials in 4D printing, exploring their synergistic potential to create dynamic and responsive structures. Nanomaterials play diverse roles as rheology modifiers, mechanical enhancers, function introducers, and more. The overarching goal of this review is to inspire researchers to delve into the vast potential of nanomaterial-enabled 4D printing, propelling advancements in this rapidly evolving field.

3.
Nat Food ; 2(5): 339-347, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-37117728

RESUMO

Pollinators support the production of the leading food crops worldwide. Organophosphates are a heavily used group of insecticides that pollinators can be exposed to, especially during crop pollination. Exposure to lethal or sublethal doses can impair fitness of wild and managed bees, risking pollination quality and food security. Here we report a low-cost, scalable in vivo detoxification strategy for organophosphate insecticides involving encapsulation of phosphotriesterase (OPT) in pollen-inspired microparticles (PIMs). We developed uniform and consumable PIMs capable of loading OPT at 90% efficiency and protecting OPT from degradation in the pH of a bee gut. Microcolonies of Bombus impatiens fed malathion-contaminated pollen patties demonstrated 100% survival when fed OPT-PIMs but 0% survival with OPT alone, or with plain sucrose within five and four days, respectively. Thus, the detrimental effects of malathion were eliminated when bees consumed OPT-PIMs. This design presents a versatile treatment that can be integrated into supplemental feeds such as pollen patties or dietary syrup for managed pollinators to reduce risk of organophosphate insecticides.

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