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1.
Comput Assist Surg (Abingdon) ; 29(1): 2327981, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38468391

RESUMO

Radiotherapy commonly utilizes cone beam computed tomography (CBCT) for patient positioning and treatment monitoring. CBCT is deemed to be secure for patients, making it suitable for the delivery of fractional doses. However, limitations such as a narrow field of view, beam hardening, scattered radiation artifacts, and variability in pixel intensity hinder the direct use of raw CBCT for dose recalculation during treatment. To address this issue, reliable correction techniques are necessary to remove artifacts and remap pixel intensity into Hounsfield Units (HU) values. This study proposes a deep-learning framework for calibrating CBCT images acquired with narrow field of view (FOV) systems and demonstrates its potential use in proton treatment planning updates. Cycle-consistent generative adversarial networks (cGAN) processes raw CBCT to reduce scatter and remap HU. Monte Carlo simulation is used to generate CBCT scans, enabling the possibility to focus solely on the algorithm's ability to reduce artifacts and cupping effects without considering intra-patient longitudinal variability and producing a fair comparison between planning CT (pCT) and calibrated CBCT dosimetry. To showcase the viability of the approach using real-world data, experiments were also conducted using real CBCT. Tests were performed on a publicly available dataset of 40 patients who received ablative radiation therapy for pancreatic cancer. The simulated CBCT calibration led to a difference in proton dosimetry of less than 2%, compared to the planning CT. The potential toxicity effect on the organs at risk decreased from about 50% (uncalibrated) up the 2% (calibrated). The gamma pass rate at 3%/2 mm produced an improvement of about 37% in replicating the prescribed dose before and after calibration (53.78% vs 90.26%). Real data also confirmed this with slightly inferior performances for the same criteria (65.36% vs 87.20%). These results may confirm that generative artificial intelligence brings the use of narrow FOV CBCT scans incrementally closer to clinical translation in proton therapy planning updates.


Assuntos
Prótons , Tomografia Computadorizada de Feixe Cônico Espiral , Humanos , Dosagem Radioterapêutica , Inteligência Artificial , Estudos de Viabilidade , Processamento de Imagem Assistida por Computador/métodos
2.
J Phys Chem B ; 128(10): 2304-2316, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38430110

RESUMO

Classical molecular dynamics (MD) simulations provide unmatched spatial and time resolution of protein structure and function. However, the accuracy of MD simulations often depends on the quality of force field parameters and the time scale of sampling. Another limitation of conventional MD simulations is that the protonation states of titratable amino acid residues remain fixed during simulations, even though protonation state changes coupled to conformational dynamics are central to protein function. Due to the uncertainty in selecting protonation states, classical MD simulations are sometimes performed with all amino acids modeled in their standard charged states at pH 7. Here, we performed and analyzed classical MD simulations on high-resolution cryo-EM structures of two large membrane proteins that transfer protons by catalyzing protonation/deprotonation reactions. In simulations performed with titratable amino acids modeled in their standard protonation (charged) states, the structure diverges far from its starting conformation. In comparison, MD simulations performed with predetermined protonation states of amino acid residues reproduce the structural conformation, protein hydration, and protein-water and protein-protein interactions of the structure much better. The results support the notion that it is crucial to perform basic protonation state calculations, especially on structures where protonation changes play an important functional role, prior to the launch of any conventional MD simulations. Furthermore, the combined approach of fast protonation state prediction and MD simulations can provide valuable information about the charge states of amino acids in the cryo-EM sample. Even though accurate prediction of protonation states in proteinaceous environments currently remains a challenge, we introduce an approach of combining pKa prediction with cryo-EM density map analysis that helps in improving not only the protonation state predictions but also the atomic modeling of density data.


Assuntos
Proteínas de Membrana , Simulação de Dinâmica Molecular , Prótons , Aminoácidos/química , Conformação Molecular , Conformação Proteica
3.
Anal Chim Acta ; 1297: 342379, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38438245

RESUMO

Here, 1,3,4-thiadiazole unit was employed as novel excited state intramolecular proton transfer (ESIPT) structure to prepare favorable fluorescent probe. High selectivity and rapid response to Cu2+ was obtained and the settling reaction was also used to recover ESIPT characteristics of probe to achieve sequential detection of H2S. Remarkable color change of solution from colorless to bright yellow and fluorescence emission from green to dark realized the visual detection of Cu2+ by naked eyes and transition of probe into portable fluorescent test strips. As expected, L-E could be utilized to quantitatively sense Cu2+ and H2S in different actual water and food samples including herbs, wine and fruits. The limits of detection for Cu2+ and H2S were as low as 34.5 nM and 38.6 nM. Also, probe L-E achieved real-time, portable, on-site quantitative detection of Cu2+ via a colorimeter and a smartphone platform with limit of detection to 90.3 nM.


Assuntos
Corantes Fluorescentes , Tiadiazóis , Vinho , Frutas , Prótons
4.
Cancer Imaging ; 24(1): 33, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439101

RESUMO

OBJECTIVES: To differentiate benign and malignant solitary pulmonary lesions (SPLs) by amide proton transfer-weighted imaging (APTWI), mono-exponential model DWI (MEM-DWI), stretched exponential model DWI (SEM-DWI), and 18F-FDG PET-derived parameters. METHODS: A total of 120 SPLs patients underwent chest 18F-FDG PET/MRI were enrolled, including 84 in the training set (28 benign and 56 malignant) and 36 in the test set (13 benign and 23 malignant). MTRasym(3.5 ppm), ADC, DDC, α, SUVmax, MTV, and TLG were compared. The area under receiver-operator characteristic curve (AUC) was used to assess diagnostic efficacy. The Logistic regression analysis was used to identify independent predictors and establish prediction model. RESULTS: SUVmax, MTV, TLG, α, and MTRasym(3.5 ppm) values were significantly lower and ADC, DDC values were significantly higher in benign SPLs than malignant SPLs (all P < 0.01). SUVmax, ADC, and MTRasym(3.5 ppm) were independent predictors. Within the training set, the prediction model based on these independent predictors demonstrated optimal diagnostic efficacy (AUC, 0.976; sensitivity, 94.64%; specificity, 92.86%), surpassing any single parameter with statistical significance. Similarly, within the test set, the prediction model exhibited optimal diagnostic efficacy. The calibration curves and DCA revealed that the prediction model not only had good consistency but was also able to provide a significant benefit to the related patients, both in the training and test sets. CONCLUSION: The SUVmax, ADC, and MTRasym(3.5 ppm) were independent predictors for differentiation of benign and malignant SPLs, and the prediction model based on them had an optimal diagnostic efficacy.


Assuntos
Fluordesoxiglucose F18 , Prótons , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Amidas
5.
Proc Natl Acad Sci U S A ; 121(11): e2314199121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38451940

RESUMO

Proton-powered c-ring rotation in mitochondrial ATP synthase is crucial to convert the transmembrane protonmotive force into torque to drive the synthesis of adenosine triphosphate (ATP). Capitalizing on recent cryo-EM structures, we aim at a structural and energetic understanding of how functional directional rotation is achieved. We performed multi-microsecond atomistic simulations to determine the free energy profiles along the c-ring rotation angle before and after the arrival of a new proton. Our results reveal that rotation proceeds by dynamic sliding of the ring over the a-subunit surface, during which interactions with conserved polar residues stabilize distinct intermediates. Ordered water chains line up for a Grotthuss-type proton transfer in one of these intermediates. After proton transfer, a high barrier prevents backward rotation and an overall drop in free energy favors forward rotation, ensuring the directionality of c-ring rotation required for the thermodynamically disfavored ATP synthesis. The essential arginine of the a-subunit stabilizes the rotated configuration through a salt bridge with the c-ring. Overall, we describe a complete mechanism for the rotation step of the ATP synthase rotor, thereby illuminating a process critical to all life at atomic resolution.


Assuntos
ATPases Mitocondriais Próton-Translocadoras , Prótons , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Conformação Proteica , Trifosfato de Adenosina , Rotação , ATPases Translocadoras de Prótons/metabolismo
6.
ACS Appl Mater Interfaces ; 16(11): 13453-13465, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38445594

RESUMO

Ionizing radiation has become widely used in medicine, with application in diagnostic techniques, such as computed tomography (CT) and radiation therapy (RT), where X-rays are used to diagnose and treat tumors. The X-rays used in CT and, in particular, in RT can have harmful side effects; hence, an accurate determination of the delivered radiation dose is of utmost importance to minimize any damage to healthy tissues. For this, medical specialists mostly rely on theoretical predictions of the delivered dose or external measurements of the dose. To extend the practical use of ionizing radiation-based medical techniques, such as magnetic resonance imaging (MRI)-guided RT, a more precise measurement of the internal radiation dose internally is required. In this work, a novel approach is presented to measure dose in liquids for potential future in vivo applications. The strategy relies on MRI contrast agents (CAs) that provide a dose-sensitive signal. The demonstrated materials are (citrate-capped) CaF2 nanoparticles (NPs) doped with Eu3+ or Fe2+/Fe3+ ions. Free electrons generated by ionizing radiation allow the reduction of Eu3+, which produces a very small contrast in MRI, to Eu2+, which induces a strong contrast. Oxidative species generated by high-energy X-rays can be measured indirectly using Fe2+ because it oxidizes to Fe3+, increasing the contrast in MRI. Notably, in the results, a strong increase in the proton relaxation rates is observed for the Eu3+-doped NPs at 40 kV. At 6 MV, a significant increase in proton relaxation rates is observed using CaF2 NPs doped with Fe2+/Fe3+ after irradiation. The presented concept shows great promise for use in the clinic to measure in vivo local ionizing radiation dose, as these CAs can be intravenously injected in a saline solution.


Assuntos
Meios de Contraste , Prótons , Raios X , Imageamento por Ressonância Magnética , Doses de Radiação
7.
Radiother Oncol ; 193: 110117, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38453539

RESUMO

BACKGROUND AND PURPOSE: Although proton therapy is increasingly being used in the treatment of paediatric and adult brain tumours, there are still uncertainties surrounding the biological effect of protons on the normal brain. Microglia, the brain-resident macrophages, have been shown to play a role in the development of radiation-induced neurotoxicity. However, their molecular and hence functional response to proton irradiation remains unknown. This study investigates the effect of protons on microglia by comparing the effect of photons and protons as well as the influence of age and different irradiated volumes. MATERIALS AND METHODS: Rats were irradiated with 14 Gy to the whole brain with photons (X-rays), plateau protons, spread-out Bragg peak (SOBP) protons or to 50 % anterior, or 50 % posterior brain sub-volumes with plateau protons. RNA sequencing, validation of microglial priming gene expression using qPCR and high-content imaging analysis of microglial morphology were performed in the cortex at 12 weeks post irradiation. RESULTS: Photons and plateau protons induced a shared transcriptomic response associated with neuroinflammation. This response was associated with a similar microglial priming gene expression signature and distribution of microglial morphologies. Expression of the priming gene signature was less pronounced in juvenile rats compared to adults and slightly increased in rats irradiated with SOBP protons. High-precision partial brain irradiation with protons induced a local microglial priming response and morphological changes. CONCLUSION: Overall, our data indicate that the brain responds in a similar manner to photons and plateau protons with a shared local upregulation of microglial priming-associated genes, potentially enhancing the immune response to subsequent inflammatory challenges.


Assuntos
Terapia com Prótons , Humanos , Criança , Ratos , Animais , Prótons , Microglia , Relação Dose-Resposta à Radiação , Raios X
8.
Sci Rep ; 14(1): 6188, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485759

RESUMO

This study correlated mild traumatic brain injury (mTBI) cognitive changes with ASL-MRI glymphatic clearance rates (GCRs) and recovery with GCR improvement. mTBI disrupts the blood brain barrier (BBB), reducing capillary mean transit time and GCRs. mTBI is clinically diagnosed utilizing history/examination findings with no physiologic biomarkers. 3D TGSE (turbo-gradient spin-echo) pulsed arterial spin-labeling 3T MRI with 7 long inversion times (TIs) assessed the signal clearance of labeled protons 2800-4000 ms postlabeling in bifrontal, bitemporal, and biparietal regions within 7 days of mTBI and once clinically cleared to resume activities. The Sport Concussion Assessment Tool Version 5 (SKAT5) and Brief Oculomotor/Vestibular Assessment evaluated injured athletes' cognitive function prior to MRIs. The pilot study demonstrated significant GCRs improvement (95% CI - 0.06 to - 0.03 acute phase; to CI-recovery CI 0.0772 to - 0.0497; P < 0.001 in frontal lobes; and parietal lobes (95% CI - 0.0584 to - 0.0251 acute; CI - 0.0727 to - 0.0392 recovery; P = 0.024) in 9 mTBI athletes (8 female, 1 male). Six age/activity-matched controls (4 females, 2 males) were also compared. mTBI disrupts the BBB, reducing GCR measured using the 3D ASL MRI technique. ASL MRI is a potential noninvasive biomarker of mTBI and subsequent recovery.


Assuntos
Concussão Encefálica , Traumatismos Craniocerebrais , Humanos , Masculino , Feminino , Prótons , Projetos Piloto , Marcadores de Spin , Imageamento por Ressonância Magnética/métodos , Circulação Cerebrovascular/fisiologia
9.
Elife ; 122024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517752

RESUMO

The vesicular monoamine transporter 2 (VMAT2) is a proton-dependent antiporter responsible for loading monoamine neurotransmitters into synaptic vesicles. Dysregulation of VMAT2 can lead to several neuropsychiatric disorders including Parkinson's disease and schizophrenia. Furthermore, drugs such as amphetamine and MDMA are known to act on VMAT2, exemplifying its role in the mechanisms of actions for drugs of abuse. Despite VMAT2's importance, there remains a critical lack of mechanistic understanding, largely driven by a lack of structural information. Here, we report a 3.1 Å resolution cryo-electron microscopy (cryo-EM) structure of VMAT2 complexed with tetrabenazine (TBZ), a non-competitive inhibitor used in the treatment of Huntington's chorea. We find TBZ interacts with residues in a central binding site, locking VMAT2 in an occluded conformation and providing a mechanistic basis for non-competitive inhibition. We further identify residues critical for cytosolic and lumenal gating, including a cluster of hydrophobic residues which are involved in a lumenal gating strategy. Our structure also highlights three distinct polar networks that may determine VMAT2 conformational dynamics and play a role in proton transduction. The structure elucidates mechanisms of VMAT2 inhibition and transport, providing insights into VMAT2 architecture, function, and the design of small-molecule therapeutics.


Assuntos
Doença de Huntington , Tetrabenazina , Humanos , Tetrabenazina/metabolismo , Tetrabenazina/farmacologia , Proteínas Vesiculares de Transporte de Monoamina/química , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , Prótons , Microscopia Crioeletrônica
10.
Sci Rep ; 14(1): 6895, 2024 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519637

RESUMO

Obesity is highly associated with Non-alcoholic fatty liver disease (NAFLD) and increased risk of liver cirrhosis and liver cancer-related death. We determined the diagnostic performance of the complex-based chemical shift technique MRI-PDFF for quantifying liver fat and its correlation with histopathologic findings in an obese population within 24 h before bariatric surgery. This was a prospective, cross-sectional, Institutional Review Board-approved study of PDFF-MRI of the liver and MRI-DIXON image volume before bariatric surgery. Liver tissues were obtained during bariatric surgery. The prevalence of NAFLD in the investigated cohort was as high as 94%. Histologic hepatic steatosis grades 0, 1, 2, and 3 were observed in 3 (6%), 25 (50%), 14 (28%), and 8 (16%) of 50 obese patients, respectively. The mean percentages of MRI-PDFF from the anterior and posterior right hepatic lobe and left lobe vs. isolate left hepatic lobe were 15.6% (standard deviation [SD], 9.28%) vs. 16.29% (SD, 9.25%). There was a strong correlation between the percentage of steatotic hepatocytes and MRI-PDFF in the left hepatic lobe (r = 0.82, p < 0.001) and the mean value (r = 0.78, p < 0.001). There was a strong correlation between MRI-derived subcutaneous adipose tissue volume and total body fat mass by dual-energy X-ray absorptiometry, especially at the L2-3 and L4 level (r = 0.85, p < 0.001). MRI-PDFF showed good performance in assessing hepatic steatosis and was an excellent noninvasive technique for monitoring hepatic steatosis in an obese population.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Prótons , Estudos Prospectivos , Estudos Transversais , Fígado/diagnóstico por imagem , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Obesidade/complicações , Obesidade/diagnóstico por imagem , Obesidade/patologia , Biópsia
11.
Biophys Chem ; 308: 107217, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490110

RESUMO

Hydrogenases are a diverse group of metalloenzymes that catalyze the conversion of H2 into protons and electrons and the reverse reaction. A subgroup is formed by the [FeFe]­hydrogenases, which are the most efficient enzymes of microbes for catalytic H2 conversion. We have determined the stability and activity of two [FeFe]­hydrogenases under high temperature and pressure conditions employing FTIR spectroscopy and the high-pressure stopped-flow methodology in combination with fast UV/Vis detection. Our data show high temperature stability and an increase in activity up to the unfolding temperatures of the enzymes. Remarkably, both enzymes reveal a very high pressure stability of their structure, even up to pressures of several kbars. Their high pressure-stability enables high enzymatic activity up to 2 kbar, which largely exceeds the pressure limit encountered by organisms in the deep sea and sub-seafloor on Earth.


Assuntos
Hidrogenase , Proteínas Ferro-Enxofre , Metaloproteínas , Hidrogenase/química , Hidrogenase/metabolismo , Proteínas Ferro-Enxofre/química , Prótons , Catálise , Hidrogênio/química , Hidrogênio/metabolismo
12.
PLoS One ; 19(3): e0298661, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512829

RESUMO

The selective separation of ions from aqueous systems, and even in the human body, is a crucial to overall environmental management and health. Nanoporous materials are widely known for their selective removal of cations from aqueous media, and therefore have been targeted for use as a pharmaceutical to treat hyperkalemia. This study investigated the detailed crystallographic molecular mechanisms that control the potassium ion selectivity in the nanoporous cubic zirconium silicate (CZS) related materials. Using time-resolved in situ Raman spectroscopy and time-resolved in situ X-ray diffraction, the selectivity mechanisms were determined to involve a synchronous cation-cation repulsion process that serves to open a favorable coordination bonding environment for potassium, not unlike the ion selectivity filter process found in potassium ion channels in proteins. Enhancement of ion exchange was observed when the CZS material was in a partial protonated state (≈3:1 Na:H), causing an expansion of the unit-cell volume, enlargement of the 7 member-ring window, and distortion of framework polyhedra, which allowed increased accessibility to the cage structures and resulted in rapid irreversible potassium ion exchange.


Assuntos
Potássio , Prótons , Silicatos , Humanos , Potássio/metabolismo , Hidrogênio , Troca Iônica , Cátions , Zircônio/química , Preparações Farmacêuticas
13.
Semin Radiat Oncol ; 34(2): 207-217, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38508785

RESUMO

The unique physical and biological characteristics of proton and carbon ions allow for improved sparing of normal tissues, decreased integral dose to the body, and increased biological effect through high linear energy transfer. These properties are particularly useful for sarcomas given their histology, wide array of locations, and age of diagnosis. This review summarizes the literature and describes the clinical situations in which these heavy particles have advantages for treating sarcomas.


Assuntos
Radioterapia com Íons Pesados , Terapia com Prótons , Sarcoma , Humanos , Prótons , Sarcoma/radioterapia
14.
J Phys Chem B ; 128(11): 2697-2706, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38447081

RESUMO

CLCF fluoride/proton antiporters move fluoride ions out of bacterial cells, leading to fluoride resistance in these bacteria. However, many details about their operating mechanisms remain unclear. Here, we report a combined quantum-mechanical/molecular-mechanical (QM/MM) study of a CLCF homologue from Enterococci casseliflavus (Eca), in accord with the previously proposed windmill mechanism. Our multiscale modeling sheds light on two critical steps in the transport cycle: (i) the external gating residue E118 pushing a fluoride in the external binding site into the extracellular vestibule and (ii) an incoming fluoride reconquering the external binding site by forcing out E118. Both steps feature competitions for the external binding site between the negatively charged carboxylate of E118 and the fluoride. Remarkably, the displaced E118 by fluoride accepts a proton from the nearby R117, initiating the next transport cycle. We also demonstrate the importance of accurate quantum descriptions of fluoride solvation. Our results provide clues to the mysterious E318 residue near the central binding site, suggesting that the transport activities are unlikely to be disrupted by the glutamate interacting with a well-solvated fluoride at the central binding site. This differs significantly from the structurally similar CLC chloride/proton antiporters, where a fluoride trapped deep in the hydrophobic pore causes the transporter to be locked down. A free-energy barrier of 10-15 kcal/mol was estimated via umbrella sampling for a fluoride ion traveling through the pore to repopulate the external binding site.


Assuntos
Antiporters , Prótons , Antiporters/química , Antiporters/metabolismo , Fluoretos/química , Modelos Moleculares , Proteínas de Membrana Transportadoras/metabolismo , Cloretos/química , Canais de Cloreto/química , Canais de Cloreto/metabolismo , Transporte de Íons
15.
J Mass Spectrom ; 59(3): e5011, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38445810

RESUMO

Benzophenone and related derivatives are widely used as photoinitiators for food packaging to cure inks or lacquers with ultraviolet (UV) light on cardboard and paper. However, there are concerns about the potential health risks of their migration into food. Knowing the physical and chemical properties of benzophenone and its derivatives could play a significant role in their quantification and analysis using chemical ionization mass spectrometry (CI-MS) methods. These parameters are evaluated using B3LYP/6-311++** density functional theory (DFT) implemented on Gaussian code. Ion-molecule chemistry through the selection of reagent ions, reaction energetics and kinetics, thermodynamic stability, and reactivity of molecules deemed to foster VOC identification and quantification via CI-MS techniques. The VOCs under study are expected to undergo exothermic reactions from H3 O+ , NH4 + , NO+ , and O2 + ions, except endothermic proton transfer from NH4 + to 2-hydroxy-4-methoxybenzophenone and 2,3,4-trihydroxy benzophenone. These compounds possess less proton affinities than NH3 and are least stable in their protonated forms. The DFT computed properties provide the basis for developing reliable and accurate methods to detect and measure the presence of benzophenone and its derivatives in packaging materials and food products.


Assuntos
Embalagem de Alimentos , Prótons , Teoria da Densidade Funcional , Benzofenonas , Qualidade dos Alimentos , Espectrometria de Massas
16.
BMC Med Imaging ; 24(1): 58, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443786

RESUMO

BACKGROUND: MULTIPLEX is a single-scan three-dimensional multi-parametric MRI technique that provides 1 mm isotropic T1-, T2*-, proton density- and susceptibility-weighted images and the corresponding quantitative maps. This study aimed to investigate its feasibility of clinical application in Parkinson's disease (PD). METHODS: 27 PD patients and 23 healthy control (HC) were recruited and underwent a MULTIPLEX scanning. All image reconstruction and processing were automatically performed with in-house C + + programs on the Automatic Differentiation using Expression Template platform. According to the HybraPD atlas consisting of 12 human brain subcortical nuclei, the region-of-interest (ROI) based analysis was conducted to extract quantitative parameters, then identify PD-related abnormalities from the T1, T2* and proton density maps and quantitative susceptibility mapping (QSM), by comparing patients and HCs. RESULTS: The ROI-based analysis revealed significantly decreased mean T1 values in substantia nigra pars compacta and habenular nuclei, mean T2* value in subthalamic nucleus and increased mean QSM value in subthalamic nucleus in PD patients, compared to HCs (all p values < 0.05 after FDR correction). The receiver operating characteristic analysis showed all these four quantitative parameters significantly contributed to PD diagnosis (all p values < 0.01 after FDR correction). Furthermore, the two quantitative parameters in subthalamic nucleus showed hemicerebral differences in regard to the clinically dominant side among PD patients. CONCLUSIONS: MULTIPLEX might be feasible for clinical application to assist in PD diagnosis and provide possible pathological information of PD patients' subcortical nucleus and dopaminergic midbrain regions.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Doença de Parkinson , Humanos , Estudos de Viabilidade , Doença de Parkinson/diagnóstico por imagem , Prótons , Dopamina
17.
Food Res Int ; 181: 114078, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38448095

RESUMO

The effects of α-amylase on of flavor perception were investigated via spectrum analysis, electronic tongue, on-line mass spectrometry, and molecular docking. Aroma release results showed that α-amylase exhibited variable release patterns of different aroma compounds. Electronic tongue analysis showed that the perception of bitterness, sweetness, sour, and saltiness was subtly increased and that of umami was significantly increased (p < 0.01) along with the increasing enzyme activity of α-amylase. Ultraviolet absorption and fluorescence spectroscopy analyses showed that static quenching occurred between α-amylase and eight flavor compounds and their interaction effects were spontaneous. One binding pocket was confirmed between the α-amylase and flavor compounds, and molecular docking simulation results showed that the hydrogen, electrostatic, and hydrophobic bonds were the main force interactions. The TYP82, TRP83, LEU173, HIS80, HIS122, ASP297, ASP206, and ARG344 were the key α-amylase amino acid residues that interacted with the eight flavor compounds.


Assuntos
Prótons , alfa-Amilases , Simulação de Acoplamento Molecular , Nariz Eletrônico , Espectrometria de Massas , Aminoácidos , Percepção
18.
Radiat Oncol ; 19(1): 34, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475815

RESUMO

BACKGROUND: FLASH therapy is a treatment technique in which radiation is delivered at ultra-high dose rates (≥ 40 Gy/s). The first-in-human FAST-01 clinical trial demonstrated the clinical feasibility of proton FLASH in the treatment of extremity bone metastases. The objectives of this investigation are to assess the toxicities of treatment and pain relief in study participants with painful thoracic bone metastases treated with FLASH radiotherapy, as well as workflow metrics in a clinical setting. METHODS: This single-arm clinical trial is being conducted under an FDA investigational device exemption (IDE) approved for 10 patients with 1-3 painful bone metastases in the thorax, excluding bone metastases in the spine. Treatment will be 8 Gy in a single fraction administered at ≥ 40 Gy/s on a FLASH-enabled proton therapy system delivering a single transmission proton beam. Primary study endpoints are efficacy (pain relief) and safety. Patient questionnaires evaluating pain flare at the treatment site will be completed for 10 consecutive days post-RT. Pain response and adverse events (AEs) will be evaluated on the day of treatment and on day 7, day 15, months 1, 2, 3, 6, 9, and 12, and every 6 months thereafter. The outcomes for clinical workflow feasibility are the occurrence of any device issues as well as time on the treatment table. DISCUSSION: This prospective clinical trial will provide clinical data for evaluating the efficacy and safety of proton FLASH for palliation of bony metastases in the thorax. Positive findings will support the further exploration of FLASH radiation for other clinical indications including patient populations treated with curative intent. REGISTRATION: ClinicalTrials.gov NCT05524064.


Assuntos
Neoplasias Ósseas , Prótons , Humanos , Neoplasias Ósseas/radioterapia , Dor , Estudos Prospectivos , Tórax
19.
Environ Sci Technol ; 58(10): 4606-4616, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38427797

RESUMO

Transforming hazardous species into active sites by ingenious material design was a promising and positive strategy to improve catalytic reactions in industrial applications. To synergistically address the issue of sluggish CO2 desorption kinetics and SO2-poisoning solvent of amine scrubbing, we propose a novel method for preparing a high-performance core-shell C@Mn3O4 catalyst for heterogeneous sulfur migration and in situ reconstruction to active -SO3H groups, and thus inducing an enhanced proton-coupled electron transfer (PCET) effect for CO2 desorption. As anticipated, the rate of CO2 desorption increases significantly, by 255%, when SO2 is introduced. On a bench scale, dynamic CO2 capture experiments reveal that the catalytic regeneration heat duty of SO2-poisoned solvent experiences a 32% reduction compared to the blank case, while the durability of the catalyst is confirmed. Thus, the enhanced PCET of C@Mn3O4, facilitated by sulfur migration and simultaneous transformation, effectively improves the SO2 resistance and regeneration efficiency of amine solvents, providing a novel route for pursuing cost-effective CO2 capture with an amine solvent.


Assuntos
Dióxido de Carbono , Prótons , Elétrons , Solventes , Aminas , Enxofre
20.
Anal Chem ; 96(10): 4146-4153, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38427846

RESUMO

Unraveling the mechanism by which native proteins are charged through electrospray ionization (ESI) has been the focus of considerable research because observable charge states can be correlated to biophysical characteristics, such as protein folding and, thus, solution conformation. Difficulties in characterizing electrosprayed droplets have catalyzed the use of molecular dynamics (MD) to provide insights into the mechanisms by which proteins are charged and transferred to the gas phase. However, prior MD studies have utilized metal ions, primarily Na+, as charge carriers, even though proteins are primarily detected as protonated ions in the mass spectra. Here, we propose a modified MD protocol for simulating discrete Grotthuss diffuse H3O+ that is capable of dynamically altering amino-acid protonation states to model electrospray charging and gaseous ion formation of model proteins, ubiquitin, and myoglobin. Application of the protocol to the evaporation of acidic droplets enables a molecular perspective of H3O+ coordination and proton transfer to/from proteins, which is unfeasible with the metal charge carriers used in previous MD studies of ESI. Our protocol recreates experimentally observed charge-state distributions and supports the charge residue model (CRM) as the dominant mechanism of native protein ionization during ESI. Additionally, our results suggest that protonation is highly specific to individual residues and is correlated to the formation of localized hydrated regions on the protein surface as droplets desolvate. Considering the use of discrete H3O+ instead of Na+, the developed protocol is a necessary step toward developing a more comprehensive model of protein ionization during ESI.


Assuntos
Simulação de Dinâmica Molecular , Prótons , Espectrometria de Massas por Ionização por Electrospray/métodos , Mioglobina/química , Íons/química , Gases/química
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