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1.
J Colloid Interface Sci ; 678(Pt B): 313-324, 2025 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-39245021

RESUMO

The water pollution caused by the abuse of antibiotics has significant harmful effects on the environment and human health. The photo-Fenton process is currently the most effective method for removing antibiotics from water, but it encounters challenges such as inadequate response to visible light, low yield and utilization of photogenerated electrons, and slow electron transport. In this study, spin state regulation was introduced into the photo-Fenton process, and the spin state of Co3+ was regulated through Ce displacement doping. The intermediate-spin state Ce-LaCoO3 could degrade 91.6 % of tetracycline within 120 min in the photo-Fenton system, which is 15.2 % higher than that of low-spin state LaCoO3. The improved degradation effect is attributed to the reasons that Ce-LaCoO3 in the intermediate-spin state have lower band gap, better charge transfer ability, and stronger adsorption capacity of H2O2, which can accelerate the redox cycle of Co2+/Co3+ and promote the generation of ·OH. This study presents a unique strategy for synthesizing efficient photo-Fenton materials to treat antibiotic wastewater effectively.


Assuntos
Antibacterianos , Peróxido de Hidrogênio , Ferro , Tetraciclina , Tetraciclina/química , Peróxido de Hidrogênio/química , Ferro/química , Antibacterianos/química , Antibacterianos/farmacologia , Processos Fotoquímicos , Cobalto/química , Poluentes Químicos da Água/química , Luz , Elétrons , Óxidos/química , Estrutura Molecular , Propriedades de Superfície , Tamanho da Partícula
2.
J Chem Phys ; 161(14)2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39382131

RESUMO

Chiral-induced-spin-selectivity of electron transport and its interplay with DNA's mechanical motion are explored in a double stranded DNA helix with spin-orbit-coupling. The mechanical degree of freedom is treated as a stochastic classical variable experiencing fluctuations and dissipation induced by the environment as well as force exerted by nonequilibrium, current-carrying electrons. Electronic degrees of freedom are described quantum mechanically using nonequilibrium Green's functions. Nonequilibrium Green's functions are computed along the trajectory for the classical variable taking into account dynamical, velocity dependent corrections. This mixed quantum-classical approach enables calculations of time-dependent spin-resolved currents. We showed that the electronic force may significantly modify the classical potential, which, at sufficient voltage, creates a bistable potential with a considerable effect on electronic transport. The DNA's mechanical motion has a profound effect on spin transport; it results in chiral-induced spin selectivity, increasing spin polarization of the current by 9% and also resulting in temperature-dependent current voltage characteristics. We demonstrate that the current noise measurement provides an accessible experimental means to monitor the emergence of mechanical instability in DNA motion. The spin resolved current noise also provides important dynamical information about the interplay between vibrational and spin degrees of freedom in DNA.


Assuntos
DNA , DNA/química , Transporte de Elétrons , Teoria Quântica , Conformação de Ácido Nucleico , Elétrons , Movimento (Física)
3.
Inorg Chem ; 63(41): 19063-19073, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39350518

RESUMO

A combination of X-ray absorption and low-temperature electronic absorption spectroscopies has been used to probe the geometric and electronic structures of the human mitochondrial amidoxime reducing component enzyme (hmARC1) in the oxidized Mo(VI) and reduced Mo(IV) forms. Extended X-ray absorption fine structure analysis revealed that oxidized enzyme possesses a 5-coordinate [MoO2(SCys)(PDT)]- (PDT = pyranopterin dithiolene) active site with a cysteine coordinated to Mo. A 5-coordinate geometry is retained in the reduced state, with the equatorial oxo being protonated. Low-temperature electronic absorption spectroscopy of hmARC1 reveals a spectrum for the oxidized enzyme that is significantly different from what has been reported for sulfite oxidase family enzymes. Time-dependent density functional theory computations on oxidized and reduced hmARC1, and a small molecule analogue for hmARC1ox, have been used to assist us in making detailed band assignments and developing a greater understanding of enzyme electronic structure contributions to reactivity. Our understanding of the hmARCred HOMO and the LUMO of the benzamidoxime substrate reveal a potential π-bonding interaction between these redox orbitals, with two-electron occupation of the substrate LUMO along the reaction coordinate activating the O-N bond for cleavage and promoting oxygen atom transfer to the Mo site.


Assuntos
Teoria da Densidade Funcional , Sulfito Oxidase , Humanos , Sulfito Oxidase/química , Sulfito Oxidase/metabolismo , Oxirredução , Elétrons , Oxirredutases/química , Oxirredutases/metabolismo , Estrutura Molecular , Molibdênio/química , Proteínas Mitocondriais/química , Proteínas Mitocondriais/metabolismo , Modelos Moleculares
4.
Luminescence ; 39(10): e4931, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39400988

RESUMO

Each of the static properties such as refractive index (n0), cation ( ∑ α i $$ \sum {\alpha}_i $$ ), and anion ( α O 2 - $$ {\alpha}_O^{2-} $$ ) oxide polarizabilities for the ternary 30Ag2O⋅xB2O3⋅(70 - x)TeO2 (30AgBTe) glasses has been predicted theoretically from those of the binary 30Ag2O-70B2O3 and 30Ag2O-70TeO2 glasses. This can be done based on two assumptions: that each of these static properties (n0, ∑ α i $$ \sum {\upalpha}_i $$ , and α O 2 - $$ {\upalpha}_{\mathrm{O}}^{2-} $$ ) can be considered as an additive property and that ternary 30AgBTe glasses can be treated as a mixture of two binary 30Ag2O-70B2O3 and 30Ag2O-70TeO2 glasses. In addition, n0 values for the ternary 30AgBTe glasses can be predicted in terms of α O 2 - $$ {\upalpha}_{\mathrm{O}}^{2-} $$ and ∑ α i $$ \sum {\upalpha}_i $$ values for the ternary 30AgBTe glasses, and these later properties can be predicted from that of two binaries like as n0 at first stage. The n0 values obtained by using two methods are exactly the same for the corresponding compositions in the studied glasses, confirming the validity of the two assumptions and the procedure described in the present work. This conclusion is valid for the ternary glasses with a fixed content of either basic former/or modifier oxides for all compositions such as xPbO⋅(40 - x)Sb2O3⋅60B2O3 and 30Ag2O⋅xB2O3⋅(70 - x)TeO2 glasses, respectively.


Assuntos
Vidro , Óxidos , Refratometria , Compostos de Prata , Vidro/química , Óxidos/química , Compostos de Prata/química , Compostos de Boro/química , Elétrons
5.
J Pak Med Assoc ; 74(10 (Supple-8)): S76-S80, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39434277

RESUMO

OBJECTIVE: To assess the electron beam dose verification, and to investigate the dependability and stability of the Startrack two-dimensional array. METHODS: The is cross-secional study was conducted from January to April 2021 at the Baghdad Centre for Radiotherapy and Nuclear Medicine, Baghdad Medical City, Baghdad, Iraq. Quality assurance measurements were made using a StarTrack two-dimensional detector on an electron beam with an energy of 12MeV at 1.5cm depth for field sizes 6cm×6cm and 14cm×14cm. The detector was positioned 100cm from the source to the surface of the linear accelerator infinity. Testing was done using the International Electrotechnical Commissioning protocol. RESULTS: There was a significant difference between field sizes 6cmx6cm and 14cmx14cm (-4.97±0.83, -2.01±0.68, respectively) (p<0.05). The beam profile measurements of penumbra, flatness and symmetry were within limits ±2 cm, and ±2 cm, 2%, respectively. The percentage of output dose curve against distance showed instability in crossline for 6cm x 6cm and 14cm x 14cm field size. CONCLUSIONS: The output dose was found to be above the tolerance level, and should be corrected before patient treatment for 12MeV energy electron beam therapy.


Assuntos
Elétrons , Elétrons/uso terapêutico , Humanos , Dosagem Radioterapêutica , Aceleradores de Partículas , Radiometria/métodos
6.
Environ Microbiol ; 26(10): e16683, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39350431

RESUMO

Sulphate-reducing microorganisms, or SRMs, are crucial to organic decomposition, the sulphur cycle, and the formation of pyrite. Despite their low energy-yielding metabolism and intense competition with other microorganisms, their ability to thrive in natural habitats often lacking sufficient substrates remains an enigma. This study delves into how Desulfovibrio desulfuricans G20, a representative SRM, utilizes photoelectrons from extracellular sphalerite (ZnS), a semiconducting mineral that often coexists with SRMs, for its metabolism and energy production. Batch experiments with sphalerite reveal that the initial rate and extent of sulphate reduction by G20 increased by 3.6 and 3.2 times respectively under light conditions compared to darkness, when lactate was not added. Analyses of microbial photoelectrochemical, transcriptomic, and metabolomic data suggest that in the absence of lactate, G20 extracts photoelectrons from extracellular sphalerite through cytochromes, nanowires, and electron shuttles. Genes encoding movement and biofilm formation are upregulated, suggesting that G20 might sense redox potential gradients and migrate towards sphalerite to acquire photoelectrons. This process enhances the intracellular electron transfer activity, sulphur metabolism, and ATP production of G20, which becomes dominant under conditions of carbon starvation and extends cell viability in such environments. This mechanism could be a vital strategy for SRMs to survive in energy-limited environments and contribute to sulphur cycling.


Assuntos
Desulfovibrio desulfuricans , Oxirredução , Sulfatos , Sulfetos , Sulfatos/metabolismo , Sulfetos/metabolismo , Desulfovibrio desulfuricans/metabolismo , Desulfovibrio desulfuricans/genética , Biofilmes/crescimento & desenvolvimento , Elétrons , Enxofre/metabolismo , Transporte de Elétrons , Compostos de Zinco
7.
J Phys Chem B ; 128(42): 10417-10426, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39392916

RESUMO

Recent efforts have sought to develop paramagnetic molecular quantum bits (qubits) as a means to store and manipulate quantum information. Emerging structure-property relationships have shed light on electron spin decoherence mechanisms. While insights within molecular quantum information science have derived from synthetic systems, biomolecular platforms would allow for the study of decoherence phenomena in more complex chemical environments and further leverage molecular biology and protein engineering approaches. Here we have employed the exchange-coupled ST = 1/2 Fe2S2 active site of putidaredoxin, an electron transfer metalloprotein, as a platform for fundamental mechanistic studies of electron spin decoherence toward spin-based biological quantum sensing. At low temperatures, decoherence rates were anisotropic, reflecting a hyperfine-dominated decoherence mechanism, standing in contrast to the anisotropy of molecular systems observed previously. This mechanism provided a pathway for probing spatial effects on decoherence, such as protein vs solvent contributions. Furthermore, we demonstrated spatial sensitivity to single point mutations via site-directed mutagenesis and temporal sensitivity for monitoring solvent isotope exchange. Thus, this study demonstrates a step toward the design and construction of biomolecular quantum sensors.


Assuntos
Metaloproteínas , Metaloproteínas/química , Metaloproteínas/metabolismo , Teoria Quântica , Elétrons , Transporte de Elétrons , Ferredoxinas/química , Ferredoxinas/metabolismo
8.
Biomed Phys Eng Express ; 10(6)2024 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-39419072

RESUMO

Purpose. Bolus is often required for targets close to or on skin surface, however, standard bolus on complex surfaces can result in air gaps that compromise dosimetry. Brass mesh boluses (RPD, Inc., Albertville, MN) are designed to conform to the patient's surface and reduce air gaps. While they have been well characterized for their use with photons, minimal characterization exists in literature for their use with electrons.Methods and materials.Dosimetric characteristics of brass mesh bolus was investigated for use with 6, 9 and 12 MeV electrons using a 10 × 10 cm2applicator on standard multi-energy LINAC. Measurements for bolus equivalence and percentage depth doses (PDDs) under brass mesh, as well as surface dose measurements were performed on solid water and a 3D printed resin breast phantom (Anycubic Photon MonoX, Shenzhen, China) using Markus®parallel-plate ionization chamber (Model 34045, PTW Freiburg, Germany), thermoluminescent detectors (TLD) and EBRT film. After obtaining surface dose measurements, these were compared to dose calculated on the Pinnacle3 treatment planning system (TPS, 16.2, Koninklijke Philips N.V.).Results. Measurements of surface dose under brass mesh showed consistently higher dose than without bolus, confirming that brass mesh can increase the PDD at surface up to ∼ 94% of dose at dmax, depending on incident electron energy. This increase is equivalent to using ∼ 7.2 mm water equivalent bolus for 6 MeV, ∼ 3.6 mm for 9 MeV and ∼ 2.2 mm bolus for 12 MeV electrons. TPS results showed close agreement within-vivomeasurements, confirming the potential for brass mesh as bolus for electron irradiation, provided blousing effect is correctly modelled.Conclusions. To increase electron surface dose, a brass mesh can be used with equivalent effect of water-density bolus varying with electron energy. Proper implementation could allow for ease of treatment, as well as increase bolus conformality in electron-only plans.


Assuntos
Cobre , Elétrons , Imagens de Fantasmas , Dosagem Radioterapêutica , Zinco , Elétrons/uso terapêutico , Humanos , Zinco/química , Cobre/química , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Aceleradores de Partículas/instrumentação , Feminino , Método de Monte Carlo , Neoplasias da Mama/radioterapia
9.
PLoS One ; 19(10): e0310222, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39446715

RESUMO

The effective elimination of nitrogen and phosphorus in urban sewage treatment was always hindered by the deficiency of organic carbon in the low C/N ratio wastewater. To overcome this organic-dependent barrier and investigate community changes after sulfur electron addition. In this study, we conducted a simulated urban wastewater treatment plant (WWTP) bioreactor by using sodium sulfate as an electron acceptor to explore the removal efficiency of characteristic pollutants before and after the addition of sulfur electron acceptor. In the actual operation of 90 days, the removal rate of sulfur electrons' chemical oxygen demand (COD), ammonia nitrogen, and total phosphorus (TP) with sulfur electrons increased to 94.0%, 92.1% and 74%, respectively, compared with before the addition of sulfur electron acceptor. Compared with no added sulfur(phase I), the reactor after adding sulfur electron acceptor(phase II) was demonstrated more robust in nitrogen removal in the case of low C/N influent. the effluent ammonia nitrogen concentration of the aerobic reactor in Pahse II was kept lower than 1.844 mg N / L after day 40 and the overall concentration of total phosphorus in phase II (0.35 mg P/L) was lower than that of phase I(0.76 mg P/L). The microbial community analysis indicates that Rhodanobacter, Bacteroidetes, and Thiobacillus, which were the predominant bacteria in the reactor, may play a crucial role in inorganic nitrogen removal, complex organic degradation, and autotrophic denitrification under the stress of low carbon and nitrogen ratios. This leads to the formation of a distinctive microbial community structure influenced by the sulfur electron receptor and its composition. This study contributes to further development of urban low-carbon-nitrogen ratio wastewater efficient and low-cost wastewater treatment technology.


Assuntos
Reatores Biológicos , Carbono , Nitrogênio , Enxofre , Águas Residuárias , Nitrogênio/metabolismo , Nitrogênio/isolamento & purificação , Águas Residuárias/química , Enxofre/metabolismo , Carbono/metabolismo , Carbono/análise , Fósforo/metabolismo , Elétrons , Purificação da Água/métodos , Poluentes Químicos da Água/análise , Eliminação de Resíduos Líquidos/métodos , Análise da Demanda Biológica de Oxigênio
10.
Compr Rev Food Sci Food Saf ; 23(5): e70009, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39289807

RESUMO

Electron beam irradiation (EBI), as a typical "green" emerging technology, can effectively alter the functional properties of starch by influencing its microstructure. This alteration enables starch to meet the current demands of consumers and the market for "health food." This paper reviews studies on modifying various starches using EBI and describes the changes in microstructure, physicochemical properties, and functional properties induced by this method. Additionally, the effects of EBI on starch-containing food products are discussed, along with issues to be addressed and research gaps in the synergistic treatment of modified starch. It is noted that the source, irradiation dose, and irradiation time all influence the effectiveness of starch modification. Given the characteristics of EBI technology, integrating physical, chemical, and biological modification methods can optimize the modification process and enhance efficiency. This technology can potentially diversify modified starch varieties and expand their applications. Furthermore, there remains significant research potential in producing modified starch using EBI technology and applying it to the food industry.


Assuntos
Elétrons , Irradiação de Alimentos , Amido , Amido/química , Amido/efeitos da radiação , Irradiação de Alimentos/métodos
11.
J Chem Phys ; 161(12)2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39319660

RESUMO

As a precursor to various reactive nitrogen species formed in biological systems, nitric oxide (•NO) participates in numerous processes, including enhancing DNA radiosensitivity in ionizing radiation-based radiotherapy. Forming guanine radical cations is another common DNA lesion resulting from ionization and oxidation damage. As such, the interaction of •NO with guanine radical cations (G•+) may contribute to the radiosensitization of •NO. An intriguing aspect of this process is the participation of multiple spin configurations in the reaction, including open-shell singlet 1,OS[G•+(↑)⋯(↓)•NO], closed-shell singlet 1,CS[G(↑↓)⋯NO+], and triplet 3[G•+(↑)⋯(↑)•NO]. In this study, the reactions of •NO with both unsubstituted guanine radical cations (in the 9HG•+ conformation) and 9-methylguanine radical cations (9MG•+, a guanosine-mimicking model compound) were investigated in the absence and presence of monohydration of radical cations. Kinetic-energy dependent reaction product ions and cross sections were measured using an electrospray ionization guided-ion beam tandem mass spectrometer. The reaction mechanisms, kinetics, and dynamics were comprehended by interpreting the reaction potential energy surface using spin-projected density functional theory, coupled cluster theory, and multiconfiguration complete active space second-order perturbation theory, followed by RRKM kinetics modeling. The combined experimental and computational findings revealed closed-shell singlet 1,CS[7-NO-9MG]+ as the major, exothermic product and triplet 3[8-NO-9MG]+ as the minor, endothermic product. Singlet biradical products were not detected due to high reaction endothermicities, activation barriers, and inherent instability.


Assuntos
Cátions , Elétrons , Guanina , Óxido Nítrico , Guanina/química , Guanina/análogos & derivados , Óxido Nítrico/química , Cinética , Radicais Livres/química , Cátions/química , Teoria da Densidade Funcional
12.
Int J Mol Sci ; 25(18)2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39337283

RESUMO

Photosystem I is a key component of primary energy conversion in oxygenic photosynthesis. Electron transfer reactions in Photosystem I take place across two parallel electron transfer chains that converge after a few electron transfer steps, sharing both the terminal electron acceptors, which are a series of three iron-sulphur (Fe-S) clusters known as FX, FA, and FB, and the terminal donor, P700. The two electron transfer chains show kinetic differences which are, due to their close geometrical symmetry, mainly attributable to the tuning of the physicochemical reactivity of the bound cofactors, exerted by the protein surroundings. The factors controlling the rate of electron transfer between the terminal Fe-S clusters are still not fully understood due to the difficulties of monitoring these events directly. Here we present a discussion concerning the driving forces associated with electron transfer between FX and FA as well as between FA and FB, employing a tunnelling-based description of the reaction rates coupled with the kinetic modelling of forward and recombination reactions. It is concluded that the reorganisation energy for FX- oxidation shall be lower than 1 eV. Moreover, it is suggested that the analysis of mutants with altered FA redox properties can also provide useful information concerning the upstream phylloquinone cofactor energetics.


Assuntos
Complexo de Proteína do Fotossistema I , Termodinâmica , Complexo de Proteína do Fotossistema I/metabolismo , Complexo de Proteína do Fotossistema I/química , Transporte de Elétrons , Cinética , Oxirredução , Modelos Moleculares , Elétrons , Proteínas Ferro-Enxofre/metabolismo , Proteínas Ferro-Enxofre/química
13.
Bioresour Technol ; 413: 131411, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39277052

RESUMO

A membrane-aerated conductive biofilm reactor (MA-CBR) was constructed for carbon-limited wastewater treatment and to reduce the stress of the electric field on nitrous oxide reductase (NosZ). Counter-diffusion with an embedded aerobic layer declined the effect of current on NosZ (K00376) for N2O reduction. Other coding genes for denitrification in cathodic membrane aerated biofilms, including K02568, K00368, K15864, K02305, and K04561, were also positively affected by the electric field and significantly accumulate in Thauera. NH4+-N oxidation can occur at the anode and cathode (membrane aeration biofilm). This cathodic synergistic NH4+-N oxidation provided more electrons to be directly utilized by the denitrifying bacteria at the cathode. Compared to the MABR, the total nitrogen removal efficiency of MA-CBR increased by 5.68 mg/L, 11.02 mg/L, and 15.63 mg/L at voltages of 0.25 V, 0.50 V, and 0.75 V, respectively.


Assuntos
Biofilmes , Reatores Biológicos , Elétrons , Membranas Artificiais , Nitrogênio , Águas Residuárias , Purificação da Água , Águas Residuárias/química , Águas Residuárias/microbiologia , Purificação da Água/métodos , Eletrodos , Desnitrificação , Oxirredutases/metabolismo , Oxirredução , Condutividade Elétrica , Thauera/metabolismo
14.
Bioresour Technol ; 413: 131539, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39332696

RESUMO

Combining the light-harvesting capabilities of photosensitizers with microbial catalysis shows great potential in solar-driven biomanufacturing. However, little information is available about the effects of photosensitizers on the photoelectron transport during the dissimilatory nitrate reduction to ammonium (DNRA) process. Herein, redox carbon dots (CDs-500) were prepared from sludge via the pyrolysis-Fenton reaction and then used to construct a photosynthetic system with Shewanella oneidensis MR-1. The MR-1/CDs-500 photosynthetic system showed a 5.9-fold increase in ammonia production (4.9 mmol(NH3)·g-1(protein)·h-1) with a high selectivity of 94.0 %. The photoelectrons were found to be stored in CDs-500 and transferred into the cells. During the inward electron transport, the intracellular CDs-500 could be used as the direct photoelectron transfer stations between outer membrane cytochrome c and DNRA-related enzymes without the involvement of CymA and MtrA. This work provides a new method for converting waste into functional catalysts and increases solar-driven NH3 production to a greater extent.


Assuntos
Amônia , Carbono , Oxirredução , Esgotos , Shewanella , Shewanella/metabolismo , Amônia/metabolismo , Carbono/farmacologia , Carbono/metabolismo , Esgotos/microbiologia , Pontos Quânticos/química , Elétrons , Fotossíntese , Fármacos Fotossensibilizantes/metabolismo
15.
J Appl Clin Med Phys ; 25(10): e14488, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39226472

RESUMO

PURPOSE: The aim of this study is to determine the effect of forcing and filling the electron density (ED) to 1.0 of the planning target volume (PTV) overdose distribution in lung SBRT treatment leading to shortening patient treatment time and increasing patient comfort by reducing MU/fraction due to ED manipulation effect. METHODS: In this study, 36 lung SBRT plans of 12 suitable patients who prescribed a total dose of 50 Gy in five fractions were generated with Monaco v.5.10 TPS using the Monte Carlo (MC) algorithm and volumetric modulated arc therapy (VMAT) technique by PTV ED values forcing as well as filling to 1.0 and comparatively assessed. The first group of plans was created by using the patient's original ED, second and third groups of plans were reoptimized by forcing and filling the ED of PTV to 1.0, respectively, therefore acquiring a new dose distribution which lead to comparatively assessment the effects of changes in ED on PTV and OAR doses. RESULTS: Assessment of treatment plans revealed that mean MU/fx numbers were decreased by 76% and 75.25% between Groups 1 and 2, Groups 1 and 3, respectively. The number of segments was also reduced in Group 1 by up to 15% compared with Groups 2 and 3. Maximum HI and CI differences for PTV between Groups 1 and 2 were less than 1% and Groups 1 and 3 were 1.5% which indicates all 3 group plans were comparable in terms of dose distribution within PTV. CONCLUSIONS: Forcing and filling the ED of PTV to 1.0 strategy has provided reduced a number of segments and MU/fx without a significant change in PTV mean and maximum doses, thereby decreasing treatment time and patient discomfort during treatment. This process should be considered in line of a potential number of patients as well as prescribed dose and MU/fx numbers.


Assuntos
Algoritmos , Neoplasias Pulmonares , Método de Monte Carlo , Órgãos em Risco , Radiocirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Radioterapia de Intensidade Modulada/métodos , Radiocirurgia/métodos , Órgãos em Risco/efeitos da radiação , Elétrons/uso terapêutico
16.
J Control Release ; 375: 614-626, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39316925

RESUMO

Controlled manufacturing and long-term stability are key challenges in the development and translation of nanomedicines. This is exemplified by the mRNA-nanoparticle vaccines against COVID-19, which require (ultra-)cold temperatures for storage and shipment. Various cryogenic protocols have been explored to prolong nanomedicine shelf-life. However, freezing typically induces high mechanical stress on nanoparticles, resulting in aggregation or destabilization, thereby limiting their performance and application. Hence, evaluating the impact of freezing and storing on nanoparticle properties already early-on during preclinical development is crucial. In the present study, we used prototypic π electron-stabilized polymeric micelles based on mPEG-b-p(HPMAm-Bz) block copolymers to macro- and microscopically study the effect of different cryoprotective excipients on nanoformulation properties like size and size distribution, as well as on freezing-induced aggregation phenomena via in-situ freezing microscopy. We show that sucrose, unlike trehalose, efficiently cryoprotected paclitaxel-loaded micelles, and we exemplify the impact of formulation composition for efficient cryoprotection. We finally establish microfluidic mixing to formulate paclitaxel-loaded micelles with sucrose as a cryoprotective excipient in a single production step and demonstrate their stability for 6 months at -20 °C. The pharmaceutical properties and preclinical performance (in terms of tolerability and tumor growth inhibition in a patient-derived triple-negative breast cancer xenograft mouse model) of paclitaxel-loaded micelles were successfully cryopreserved. Together, our efforts promote future pharmaceutical development and translation of π electron-stabilized polymeric micelles, and they illustrate the importance of considering manufacturing and storage stability issues early-on during nanomedicine development.


Assuntos
Crioprotetores , Estabilidade de Medicamentos , Micelas , Paclitaxel , Paclitaxel/administração & dosagem , Paclitaxel/química , Animais , Humanos , Crioprotetores/química , Feminino , Camundongos , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Polietilenoglicóis/química , Linhagem Celular Tumoral , Microfluídica , Polímeros/química , Camundongos Nus , Elétrons , Composição de Medicamentos , Nanopartículas/química
17.
Rapid Commun Mass Spectrom ; 38(23): e9910, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39287024

RESUMO

RATIONALE: Isomerism can be an important aspect in pharmaceutical drug development. Identification of isomers can provide insights into drug pharmacology and contribute to better design of drug molecules. The general approaches to differentiate isomers include Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and circular dichroism. Additionally, a commonly used method to differentiate isomers is liquid chromatography coupled with mass spectrometry (LC-MS). Notably, LC-MS is routinely applied to leucine and isoleucine differentiation to facilitate protein sequencing. This work focuses on isomer differentiation of widely employed thio-succinimide structure bridging the antibody backbone and linker-payload of antibody-drug conjugates (ADCs). Thio-succinimide hydrolysis stabilizes the payload-protein structure while generating a pair of constitutional isomers: thio-aspartyl and thio-isoaspartyl. METHODS: This paper introduces a hybrid method using ligand binding assay (LBA) and liquid chromatography coupled with tandem MS (LC-MS/MS) to reveal isomerization details of thio-succinimide hydrolysis over time in plasma samples incubated with ADC. Application of two orthogonal dissociation methods, collision-induced dissociation (CID) and electron-activated dissociation (EAD) revealed different MS/MS spectra for this pair of isomers. This observation enables a unique approach in distinguishing thio-succinimide hydrolysis isomers. RESULTS: We observed signature [R1 + Thio + 57 + H]+, [R2 + Succ + H2O - 57 + H]+, and [R2 + Succ + H2O - 44 + 2H]2+ product ions (Succ = succinimide) that differentiated thio-aspartyl and thio-isoaspartyl isomers using EAD. A newly discovered [R2 + ThioSucc + H2O - 44 + 2H]2+ ion also served as additional evidence that further supported our findings. CONCLUSIONS: This study is a first-to-date identification of thio-succinimide hydrolysis isomers without using synthesized reference materials. This approach should be applicable to all thio-succinimide-linked molecules. Correct identification of thio-succinimide hydrolysis isomers may eventually benefit the development of ADCs in the future.


Assuntos
Succinimidas , Compostos de Sulfidrila , Isomerismo , Compostos de Sulfidrila/química , Succinimidas/química , Elétrons , Espectrometria de Massas em Tandem/métodos , Hidrólise , Imunoensaio
18.
Cancer Radiother ; 28(5): 463-473, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39304401

RESUMO

Ultra-high dose rate external beam radiotherapy (UHDR-RT) uses dose rates of several tens to thousands of Gy/s, compared with the dose rate of the order of a few Gy/min for conventional radiotherapy techniques, currently used in clinical practice. The use of such dose rate is likely to improve the therapeutic index by obtaining a radiobiological effect, known as the "FLASH" effect. This would maintain tumor control while enhancing tissues protection. To date, this effect has been achieved using beams of electrons, photons, protons, and heavy ions. However, the conditions required to achieve this "FLASH" effect are not well defined, and raise several questions, particularly with regard to the definition of the prescription, including dose fractionation, irradiated volume and the temporal structure of the pulsed beam. In addition, the dose delivered over a very short period induces technical challenges, particularly in terms of detectors, which must be mastered to guarantee safe clinical implementation. IRSN has carried out an in-depth literature review of the UHDR-RT technique, covering various aspects relating to patient radiation protection: the radiobiological mechanisms associated with the FLASH effect, the used temporal structure of the UHDR beams, accelerators and dose control, the properties of detectors to be used with UHDR beams, planning, clinical implementation, and clinical studies already carried out or in progress.


Assuntos
Neoplasias , Dosagem Radioterapêutica , Humanos , Neoplasias/radioterapia , Proteção Radiológica/métodos , Órgãos em Risco/efeitos da radiação , Fótons/uso terapêutico , Fracionamento da Dose de Radiação , Radioterapia de Alta Energia/métodos , Elétrons/uso terapêutico , Terapia com Prótons/métodos
19.
Phys Chem Chem Phys ; 26(39): 25524-25532, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39328041

RESUMO

Tumor hypoxia hampers radiotherapy efficacy, necessitating radiosensitizers. Substituted nucleobases offer advantages as radiosensitizers. They can be incorporated into DNA with minimal gene-expression alteration, selectively targeting tumor cells and having lower toxicity to normal tissues. They possess higher electron affinity than native DNA, facilitating rapid electron attachment for cancer-cell damage. Despite advancements, exploration beyond uracil nucleobases remains limited. Herein, we investigated electron attachment to potential radiosensitizers, specifically 5-halo-2'-deoxycytidine-3'-monophosphates (5X-3'-dCMPH). Our findings indicate that 5X-3'-dCMPH nucleotides possess higher electron affinity than unsubstituted 3'-dCMPH, suggesting halogenated nucleotides are better electron acceptors. Moreover, the high vertical detachment energy (VDE) implies minimal auto-detachment, and the dissociative electron attachment (DEA) pathways suggest that dehalogenation is the favored process for halogenated systems, supported by low dissociation barriers. Notably, 5Br-3'-dCMPH and 5I-3'-dCMPH exhibit nearly barrier-free dissociation after electron attachment, and thus, they may preferentially act as superior radiosensitizers.


Assuntos
Elétrons , Halogenação , Radiossensibilizantes , Radiossensibilizantes/química , Nucleotídeos/química
20.
Int J Biol Macromol ; 279(Pt 4): 135369, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39260656

RESUMO

The influence of electron beam irradiation (EBI) treatment on the modification of gelatin-galactose glycosylation was thoroughly examined. The results of the degree of grafting and browning revealed that EBI triggered the glycosylation reaction of gelatin. The degree of glycosylation exhibited a gradual increase with the rising irradiation dose, reaching a maximum of 25 kGy. Moreover, the irradiation process opened up gelatin's internal structure, exposing its hydrophobic groups. This exposure led to an enhancement in sample surface hydrophobicity. The fluorescence intensity at the maximum emission wavelength of the fluorescence spectra decreased; Fourier infrared spectroscopy demonstrated a new absorption peak at 1074 cm-1 for the glycosylation product. These findings substantiate that gelatin formed a new product through covalent bonding with galactose. Glycosylation boosted the emulsification stability of gelatin from 1.92 min to 10.42 min and improved its emulsification and rheological properties. These outcomes affirm that EBI can effectively induce the glycosylation reaction of gelatin, thereby enhancing its functional properties. In addition, EBI has the potential to supplant the conventional heating glycosylation method. This study lays a solid theoretical foundation for the future application of glycosylation and gelatin.


Assuntos
Elétrons , Gelatina , Gelatina/química , Glicosilação , Interações Hidrofóbicas e Hidrofílicas , Fenômenos Químicos , Galactose/química , Reologia , Emulsões/química
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