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BACKGROUND: To examine the application of quantitative 2-dimensional phase-contrast magnetic resonance imaging (2D PC-MRI) for treating patients with pelvic congestion syndrome (PCS). MATERIALS AND METHODS: We conducted a retrospective cross-sectional analysis by using quantitative 2D PC-MRI data enrolled between April 2017 and Sep 2023. In addition, 32 healthy female controls (HCs) were included. RESULTS: Most patients with PCS presented with chronic pelvic pain and more than half had extra-pelvic venous symptoms (80/81, 98% and 45/81, 56%, respectively). Quantitative 2D PC-MRI analyzed the 81 patients with PCS, 239 patients without PCS, and 32 HCs. The patients with PCS had higher stroke volume (SV), absolute SV (ASV), and mean flux (MF) in the calf region (interstitial pixel shift) than did the HCs. In the left gonadal vein, the patients with PCS had higher SV, backward flow volume (BFV), ASV, and MF and lower forward flow volume (FFV), stroke distance (SD), and mean velocity (MV) than did the HCs. However, the patients with PCS had lower SV, FFV, MF, SD, and MV in the great saphenous veins. Quantitative 2D PC-MRI analysis revealed that the PCS group had higher SV, FFV, BFV, ASV, and MF in the calf region than did the non-PCS group. The variables that most strongly differentiated the patients with PCS from the HCs were SV in the great saphenous veins, SD in the great saphenous veins and left gonadal vein, and MV in the great saphenous veins and left gonadal vein. Caudal flow in the left gonadal vein was identified in half of the patients with PCS (39/81, 48.1%); 14 of them received embolization for left gonadal vein. CONCLUSIONS: In additional to providing an objective 3-dimensional morphology of the pelvic veins and extra-pelvic leaks, quantitative 2D PC-MRI analysis reveals distinct hemodynamic profiles between patients with PCS, those without PCS, and HCs, especially in the gonadal veins and regional perfusion of the calves.
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This study examines the predictive value of elevated N-terminal-pro brain natriuretic peptide (NT-pro BNP) levels for mortality among patients with end-stage renal disease (ESRD). Data from 768 ESRD patients, excluding those with cancer or lost follow-up, were analyzed using Kaplan-Meier curves and Cox proportional hazards models over three years. Results indicated that patients with very high NT-pro BNP levels had shorter average survival times and a significantly higher risk of mortality (hazard ratio 1.43). Advanced age, ICU admission, and comorbidities like cerebrovascular diseases and chronic obstructive pulmonary disease also contributed to increased mortality risks. Thus, elevated NT-pro BNP is an independent risk factor for mortality in ESRD patients.
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BACKGROUND: Good nursing leadership management positively correlates with patient care quality and an organization's performance. Plans to nurture top-notch talents and strengthen management functions are essential to retain key talents and achieve sustainability. The leadership training for nursing staff should begin early to cope with complex clinical situations. OBJECTIVES: To compare the impact of leadership training on high-performing young nurses' (young nursing elite) management functions and team behavior. SETTING: A public teaching hospital in Taipei, Taiwan. METHODS: This research implemented a longitudinal quasi-experimental study with a fixed time series design; the target subjects were youth nursing elites who received training, along with their direct managers and peers, for a total of 102 participants. The training course intervention included the classroom teaching of leadership management functions, arranging internships in the hospital's internal administrative units and professional nursing institutions, and the direct managers sharing their experiences during teaching. We measured the outcome indicators before the course intervention, at the end of the course intervention, and three months after using the management function and team behavior scales. RESULTS: The mean score of the direct managers' assessments regarding the youth nursing elite's pre-test team behavior was 4.18. This improved by 0.68 points (p < .001) after the program intervention and improved by 0.65 points (p < .001) three months after the program compared to the pre-test. There was no statistically significant difference between the two groups as analyzed using GEE. The mean score of the pre-test self-assessment management function of the young nursing elite was 3.27. This improved by 1.06 points (p < .001) after the program intervention and by 1.14 points (p < .001) three months after the program compared to the pre-test. There was no statistically significant difference between the three groups using GEE analysis. CONCLUSIONS: Leadership training enhances young nursing professionals' leadership function and team behavior.
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Hospitais de Ensino , Liderança , Humanos , Taiwan , Estudos Longitudinais , Feminino , Masculino , Adulto , Recursos Humanos de Enfermagem Hospitalar/educaçãoRESUMO
Defects in conformal field theory (CFT) are of significant theoretical and experimental importance. The presence of defects theoretically enriches the structure of the CFT, but at the same time, it makes it more challenging to study, especially in dimensions higher than two. Here, we demonstrate that the recently-developed theoretical scheme, fuzzy (non-commutative) sphere regularization, provides a powerful lens through which one can dissect the defect of 3D CFTs in a transparent way. As a notable example, we study the magnetic line defect of 3D Ising CFT and clearly demonstrate that it flows to a conformal defect fixed point. We have identified 6 low-lying defect primary operators, including the displacement operator, and accurately extract their scaling dimensions through the state-operator correspondence. Moreover, we also compute one-point bulk correlators and two-point bulk-defect correlators, which show great agreement with predictions of defect conformal symmetry, and from which we extract various bulk-defect operator product expansion coefficients. Our work demonstrates that the fuzzy sphere offers a powerful tool for exploring the rich physics in 3D defect CFTs.
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BACKGROUND: Patients with major depressive disorder (MDD) exhibit atypical brain activities in the frontal, temporal, and parietal lobes. The study aimed to investigate the effects of standardized weighted low-resolution electromagnetic tomography Z-score neurofeedback (swLZNFB) on symptoms of depression and anxiety, electroencephalography (EEG) parameters, and deep brain activities in patients with MDD. METHOD: Forty-eight patients with MDD comorbid with anxiety symptoms were assigned to the swLZNFB group and the control group. Participants completed the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) and a 5-minute resting EEG at the pre-and post-tests. The swLZNFB group received ten sessions of one-hour treatment twice weekly. The control group received treatment as usual. The scores for BDI-II and BAI, number of EEG abnormalities, percentage of EEG abnormalities, and current source density (CSD) measured in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and amygdala were compared at pre-and post-tests between the two groups. RESULTS: There were decreased scores of BDI-II and BAI, number of EEG abnormalities, and percentage of EEG abnormalities at post-test compared with pre-test in the swLZNFB group, and lower scores of BDI-II and BAI at post-test in the swLZNFB group compared with the control group. Moreover, decreased CSD of beta1 and beta3 in the PFC, ACC, PCC, and amygdala at post-test compared to pre-test in the swLZNFB group. LIMITATIONS: Not a randomized controlled trial. CONCLUSION: Ten sessions of swLZNFB reduced clinical symptoms and atypical brain activities, it serves as a potential psychological intervention for patients with MDD.
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Transtorno Depressivo Maior , Neurorretroalimentação , Humanos , Neurorretroalimentação/métodos , Transtorno Depressivo Maior/terapia , Ansiedade/terapia , Eletroencefalografia , Transtornos de Ansiedade/terapiaRESUMO
Dual-targeting anticancer agents 4-29 are designed by combining the structural features of purine-type microtubule-disrupting compounds and HDAC inhibitors. A library of the conjugate compounds connected by appropriate linkers was synthesized and found to possess HDACs inhibitory activity and render microtubule fragmentation by activating katanin, a microtubule-severing protein. Among various zinc-binding groups, hydroxamic acid shows the highest inhibitory activity of Class I HDACs, which was also reconfirmed by three-dimensional quantitative structure-activity relationship (3D-QSAR) pharmacophore prediction. The purine-hydroxamate conjugates exhibit enhanced cytotoxicity against MDA-MB231 breast cancer cells, H1975 lung cancer cells, and various clinical isolated non-small-cell lung cancer cells with different epidermal growth factor receptor (EGFR) status. Pyridyl substituents could be used to replace the C2 and N9 phenyl moieties in the purine-type scaffold, which can help to improve the solubility under physiological conditions, thus increasing cytotoxicity. In mice treated with the purine-hydroxamate conjugates, the tumor growth rate was significantly reduced without causing toxic effects. Our study demonstrates the potential of the dual-targeting purine-hydroxamate compounds for cancer monotherapy.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Linhagem Celular Tumoral , Histona Desacetilases/metabolismo , Antineoplásicos/química , Inibidores de Histona Desacetilases/química , Microtúbulos/metabolismo , Purinas/farmacologia , Ácidos Hidroxâmicos/química , Relação Estrutura-Atividade , Proliferação de CélulasRESUMO
Parasitoid wasps control pests via a precise attack leading to the death of the pest. However, parasitoid larvae exhibit self-protection strategies against bracovirus-induced reactive oxygen species impairment. This has a detrimental effect on pest control. Here, we report a strategy for simulating Microplitis bicoloratus bracovirus using Mix-T dsRNA targeting 14 genes associated with transcription, translation, cell-cell communication, and humoral signaling pathways in the host, and from wasp extracellular superoxide dismutases. We implemented either one-time feeding to the younger instar larvae or spraying once on the corn leaves, to effectively control the invading pest Spodoptera frugiperda. This highlights the conserved principle of "biological pest control," as elucidated by the triple interaction of parasitoid-bracovirus-host in a cooperation strategy of bracovirus against its pest host.
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Polydnaviridae , Vespas , Animais , Spodoptera , Polydnaviridae/genética , Interações Hospedeiro-Parasita , LarvaRESUMO
In this paper, we study the effect of microbial fermentation on the nutrient composition and flavor of sweet potato slurry, different strains of Aspergillus niger, Saccharomyces cerevisiae, Lactobacillus plantarum, Bacillus coagulans, Bacillus subtilis, Lactobacillus acidophilus, and Bifidobacterium brevis were employed to ferment sweet potato slurry. After 48 h of fermentation with different strains (10% inoculation amount), we compared the effects of several strains on the nutritional and functional constituents (protein, soluble dietary fiber, organic acid, soluble sugar, total polyphenol, free amino acid, and sensory characteristics). The results demonstrated that the total sugar level of sweet potato slurry fell significantly after fermentation by various strains, indicating that these strains can utilize the nutritious components of sweet potato slurry for fermentation. The slurry's total protein and phenol concentrations increased significantly, and many strains demonstrated excellent fermentation performance. The pH of the slurry dropped from 6.78 to 3.28 to 5.95 after fermentation. The fermentation broth contained 17 free amino acids, and the change in free amino acid content is closely correlated with the flavor of the sweet potato fermentation slurry. The gas chromatography-mass spectrometry results reveal that microbial fermentation can effectively increase the kinds and concentration of flavor components in sweet potato slurry, enhancing its flavor and flavor profile. The results demonstrated that Aspergillus niger fermentation of sweet potato slurry might greatly enhance protein and total phenolic content, which is crucial in enhancing nutrition. However, Bacillus coagulans fermentation can enhance the concentration of free amino acids in sweet potato slurry by 64.83%, with a significant rise in fresh and sweet amino acids. After fermentation by Bacillus coagulans, the concentration of lactic acid and volatile flavor substances also achieved its highest level, which can considerably enhance its flavor. The above results showed that Aspergillus niger and Bacillus coagulans could be the ideal strains for sweet potato slurry fermentation.
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Background: Lower extremity venous disease (LEVD) is a complex disorder, and determining the etiology of LEVD is paramount for treatment selection. Two-dimensional phase-contrast magnetic resonance imaging (2D PC-MRI) can provide an objective measure of hemodynamic status and may help differentiate between different etiologies of LEVD. A total of 271 participants, including 256 symptomatic patients with venous lower extremity disease and 15 healthy volunteers, were collected in this cohort study. Methods: It is a single-center prospective observational study using 2D PC-MRI analysis to assess the hemodynamic characteristics of patients with LEVD among participants recruited between April 2017 and October 2021 at a tertiary hospital. The approval institutional review board number for this study were 201802137B0, 201901058B0, 202100938B0, and 202102344B0. Participants were classified as venous reflux (VR) and venous obstruction (VO) by standard ultrasonography. 2D PC-MRI by 1.5 T scanner revealed stroke volume (SV), forward flow volume (FFV), absolute stroke volume (ASV), mean flux (MF), velocity time integral (VTI), and mean velocity (MV) for each selected venous segments. Results: 2D PC-MRI assessed 167 diseased legs from the 116 VR patients [mean age ± standard deviation (SD): 57.9±12.8 years; 39 males] and 113 diseased legs from the 95 VO patients (mean age ± SD: 66.4±12.8 years; 42 males). 2D PC-MRI analysis demonstrated discrimination ability to differentiate from VR to VO [SV, FFV, ASV, MF, VTI, and MV in the various venous segments, respectively, P≤0.001; area under the curve (AUC) =62-68.8%, P≤0.001 by Mann-Whitney U test]. The ratio data (morbid limb to normal limb) in the same individual with single-leg disease revealed differences between VR and VO (SV, FFV, ASV, and MF in the various venous segments, respectively; P<0.05; AUC =60.2-68.7%, P≤0.05 by Mann-Whitney U test). The most favorable differentiating variables of ratios were FFV in the great saphenous veins [AUC =68.7%, 95% confidence interval (CI): 59.8-77.6%] and ASV in the external iliac veins (AUC =67.4%, 95% CI: 58.7-76.2%). Conclusions: Quantitative 2D PC-MRI analysis is capable of differentiating VR from VO. It also provides an important diagnostic capability for preoperative evaluation.
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Conformal field theory (CFT) plays a crucial role in the study of various critical phenomena. While much attention has been paid to the critical exponents of different universalities, which correspond to the conformal dimensions of CFT primary fields, other important and intricate data such as operator product expansion (OPE) coefficients governing the fusion of two primary fields, have remained largely unexplored, especially in dimensions higher than 2D (or equivalently, 1+1D). Motivated by the recently proposed fuzzy sphere regularization, we investigate the operator content of 3D Ising criticality from a microscopic perspective. We first outline the procedure for extracting OPE coefficients on the fuzzy sphere and then compute 13 OPE coefficients of low-lying CFT primary fields. Our results are highly accurate and in agreement with the numerical conformal bootstrap data of 3D Ising CFT. Moreover, we were able to obtain 4 OPE coefficients, including f_{T_{µν}T_{ρη}ε}, which were previously unknown, thus demonstrating the superior capabilities of our scheme. Expanding the horizon of the fuzzy sphere regularization from the state perspective to the operator perspective opens up new avenues for exploring a wealth of new physics.
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Cerebral Small Vessel Disease (CSVD) frequently affects the elderly, with inflammation playing a crucial role in related health complications, including dementia, stroke, and SVD. Studies, including animal experiments, indicate a strong link between inflammation and SVD progression. The Neutrophil-Lymphocyte Ratio (NLR) serves as a possible biomarker for ongoing inflammatory risks. A total of 720 adults aged 50 years or older from the community-based I-Lan Longitudinal Aging Study were included in this study. General linear regression and ordinally logistic regression analyses were performed to evaluate the association between NLR and CSVD. We further examined the presence of lacune, microbleed, and white matter hyperintensity (WMH) on brain MRI, which were used to construct a combined CSVD score. The NLR was positively associated with WMH (adjusted r = 0.109, p = 0.003), microbleed (adjusted r = 0.102, p = 0.006), and lacune (adjusted r = 0.100, p = 0.008). After adjustments for smoking, drinking, and physical activity in the ordinal logistic regression analysis, age, gender, brachial Systolic Blood Pressure (SBP), fasting glucose, LDL-cholesterol, and Hs-CRP were compared among subjects with low tertile (T1), medium tertile (T2) and high tertile (T3) NLR. The results showed that T2 vs. T1 had an odds ratio of 1.23 (0.86-1.77); and T3 vs. T1 had an odds ratio of 1.87 (1.29-2.71) of CSVD scores in four groups (zero (reference group), one, two, and three or more). NLR could be used to assess the state of inflammation in cerebral vessels. A significant and positive correlation between NLR and CSVD was verified in this study. However, the practical clinical application of NLR in CSVD patients and prognosis prediction should be validated through more scientific attempts.
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Neuronally triggered phosphorylation drives the calibrated and cyclable assembly of the reflectin signal transducing proteins, resulting in their fine tuning of colours reflected from specialized skin cells in squid for camouflage and communication. In close parallel to this physiological behaviour, we demonstrate for the first time that electrochemical reduction of reflectin A1, used as a surrogate for charge neutralization by phosphorylation, triggers voltage-calibrated, proportional and cyclable control of the size of the protein's assembly. Electrochemically triggered condensation, folding and assembly were simultaneously analysed using in situ dynamic light scattering, circular dichroism and UV absorbance spectroscopies. The correlation of assembly size with applied potential is probably linked to reflectin's mechanism of dynamic arrest, which is controlled by the extent of neuronally triggered charge neutralization and the corresponding fine tuning of colour in the biological system. This work opens a new perspective on electrically controlling and simultaneously observing reflectin assembly and, more broadly, provides access to manipulate, observe and electrokinetically control the formation of intermediates and conformational dynamics of macromolecular systems.
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Decapodiformes , Proteínas , Animais , Proteínas/química , Decapodiformes/química , Decapodiformes/metabolismo , Pele/metabolismo , Fosforilação , Dicroísmo CircularRESUMO
The current SARS-CoV-2 pandemic highlights our fragility when we are exposed to emergent viruses either directly or through zoonotic diseases. Fortunately, our knowledge of the biology of those viruses is improving. In particular, we have more and more structural information on virions, i.e., the infective form of a virus that includes its genomic material and surrounding protective capsid, and on their gene products. It is important to have methods that enable the analyses of structural information on such large macromolecular systems. We review some of those methods in this paper. We focus on understanding the geometry of virions and viral structural proteins, their dynamics, and their energetics, with the ambition that this understanding can help design antiviral agents. We discuss those methods in light of the specificities of those structures, mainly that they are huge. We focus on three of our own methods based on the alpha shape theory for computing geometry, normal mode analyses to study dynamics, and modified Poisson-Boltzmann theories to study the organization of ions and co-solvent and solvent molecules around biomacromolecules. The corresponding software has computing times that are compatible with the use of regular desktop computers. We show examples of their applications on some outer shells and structural proteins of the West Nile Virus.
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COVID-19 , Humanos , SARS-CoV-2 , Proteínas do Capsídeo , Capsídeo , SolventesRESUMO
High energy resource demand has led to the rapid development of hydrogen as a clean fuel through electrolytic water splitting. The exploration of high-performance and cost-effective electrocatalysts for water splitting is a challenging task to obtain renewable and clean energy. However, the sluggish kinetics of oxygen evolution reaction (OER) greatly hindered its application. Herein, a novel oxygen plasma-treated graphene quantum dots embedded Ni-Fe Prussian blue analogue (O-GQD-NiFe PBA) is proposed as a highly active electrocatalysts for OER. Furthermore, the defect induced by GQD can provide an abundant lattice mismatch in the matrix of NiFe PBA, which further facilitates faster electron transport and kinetic performance. After optimization, the as-assembled O-GQD-NiFe PBA exhibits excellent electrocatalytic performance towards OER with a low overpotential of 259 mV for reaching a current density of 10 mA cm-2 and impressive long-term stability for 100 h in an alkaline solution. This work broadens the scope of metal-organic frameworks (MOF) and high-functioning carbon composite as an active material for energy conversion systems.
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Necrotizing fasciitis (NF) represents a rapidly progressive, life-threatening infection involving the fascia and subcutaneous tissue. Early diagnosis and intervention are crucial to treat, especially in diabetic patients. Case presentation: This case report presents on a patient with diabetes mellitus rapidly developed a NF of the upper extremities following a minor trauma in the palmar of greater thenar. In the initial stages of her hospital admission, severe hand soft tissue infection, and systemic toxicity is the most prominent clinical manifestation. During her hospitalization, efficacious multidisciplinary treatment was carried out to avoid severe consequences. Clinical discussion and conclusion: The objective of this case report is to present a successful individual strategy in a complex case to standardize the treatment process. Accurate and standardized management can improve the prognosis of patients affected from upper extremities NF of diabetic avoiding and severe complications and saving lives.
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OBJECTIVES: The common practice is to remove symptomatic common bile duct (CBD) stones in patients. This study aimed to investigate the factors affecting the percutaneous transhepatic removal of CBD stones. METHODS: We retrospectively analyzed the data of 100 patients (66 men and 34 women; age: 25-105 years, mean 79.1 years) with symptomatic CBD stones who underwent percutaneous transhepatic stone removal (PTSR) from January 2010 through October 2019. After balloon dilation of the ampulla of Vater or bilioenteric anastomosis, the stones were pushed out of the CBD into the small bowel with a balloon catheter. If failed, basket lithotripsy was performed. Technical success was defined as complete clearance of the bile ducts on a cholangiogram. RESULTS: The technical success rate was 83%, and achieved 90.2% in patients with altered gastroduodenal/pancreatobiliary anatomy. Multivariable analysis revealed that CBD diameter (odds ratio [OR]: 506.460, p = 0.015), failed ERCP (OR: 16.509, p = 0.004), Tokyo guidelines TG18/TG13 severity (grade III; OR: 60.467, p = 0.006), and left-sided transhepatic approach (OR: 21.621, p = 0.012) were risk factors for technical failure. The appropriate cutoff CBD size was 15.5 mm (area under the curve: 0.91). CBD stone size, radiopacity of stones, and CBD angle between retroduodenal and pancreatic portion did not influence technical success. CONCLUSIONS: PTSR is effective for CBD stone removal in older adults and individuals with altered gastrointestinal tract anatomy. The aforementioned risk factors for technical failure should be considered in preoperative evaluation before PTSR to improve the success rate. KEY POINTS: ⢠PTSR is effective in symptomatic CBD stone management among older adults and individuals with altered anatomy. Investigating clinical /anatomic factors can guide radiologists toward a more comprehensive preoperative evaluation to maximize the success rate. ⢠Our data indicate that dilated CBD (diameter ≥ 15.5 mm) and left-sided PTBDs reduce the technical success rate by 506-fold and 22-fold, respectively. ⢠Clinical factors such as previous failed ERCP for stone removal and higher severity of acute cholangitis lessen the technical success rate.
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Coledocolitíase , Cálculos Biliares , Masculino , Humanos , Feminino , Idoso , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Coledocolitíase/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/cirurgia , Ducto Colédoco/diagnóstico por imagem , Ducto Colédoco/cirurgia , Colangiopancreatografia Retrógrada EndoscópicaRESUMO
BACKGROUND: Amyotrophic lateral sclerosis (ALS) associated with TAR DNA-binding protein 43 (TDP-43) aggregation has been considered as a lethal and progressive motor neuron disease. Recent studies have shown that both C-terminal TDP-43 (C-TDP-43) aggregates and oligomers were neurotoxic and pathologic agents in ALS and frontotemporal lobar degeneration (FTLD). However, misfolding protein has long been considered as an undruggable target by applying conventional inhibitors, agonists, or antagonists. To provide this unmet medical need, we aim to degrade these misfolding proteins by designing a series of proteolysis targeting chimeras (PROTACs) against C-TDP-43. METHODS: By applying filter trap assay, western blotting, and microscopy imaging, the degradation efficiency of C-TDP-43 aggregates was studied in Neuro-2a cells overexpressing eGFP-C-TDP-43 or mCherry-C-TDP-43. The cell viability was characterized by alarmarBlue assay. The beneficial and disaggregating effects of TDP-43 PROTAC were examined with the YFP-C-TDP-43 transgenic C. elegans by motility assay and confocal microscopy. The impact of TDP-43 PROTAC on C-TDP-43 oligomeric intermediates was monitored by fluorescence lifetime imaging microscopy and size exclusion chromatography in the Neuro-2a cells co-expressing eGFP-C-TDP-43 and mCherry-C-TDP-43. RESULTS: Four PROTACs with different linker lengths were synthesized and characterized. Among these chimeras, PROTAC 2 decreased C-TDP-43 aggregates and relieved C-TDP-43-induced cytotoxicity in Neuro-2a cells without affecting endogenous TDP-43. We showed that PROTAC 2 bound to C-TDP-43 aggregates and E3 ligase to initiate ubiquitination and proteolytic degradation. By applying advanced microscopy, it was further shown that PROTAC 2 decreased the compactness and population of C-TDP-43 oligomers. In addition to cellular model, PROTAC 2 also improved the motility of transgenic C. elegans by reducing the C-TDP-43 aggregates in the nervous system. CONCLUSIONS: Our study demonstrated the dual-targeting capacity of the newly-designed PROTAC 2 against both C-TDP-43 aggregates and oligomers to reduce their neurotoxicity, which shed light on the potential drug development for ALS as well as other neurodegenerative diseases.
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Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Animais , Esclerose Lateral Amiotrófica/metabolismo , Doenças Neurodegenerativas/genética , Proteólise , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Ligação a DNA/metabolismo , Animais Geneticamente ModificadosRESUMO
Bacillus subtilis has been extensively studied for its ability to inhibit the growth of harmful microorganisms and its high protease activity. In this study, Bacillus subtilis was used to ferment gluten and assess the effects of the fermentation process on the physicochemical, microstructure and antioxidant properties of gluten. The results of Fourier infrared spectroscopy (FT-IR) and circular chromatography (CD) showed a significant decrease in the content of α-helix structures and a significant increase in the content of ß-sheet structures in gluten after fermentation (p < 0.05). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that glutenin was degraded into small molecular peptides with a molecular weight of less than 26 kDa after 24 h of fermentation; meanwhile, the fermentation process significantly increased the free amino acid content of the samples (p < 0.05), reaching 1923.38 µg/mL at 120 h of fermentation, which was 39.46 times higher than that at 24 h of fermentation (p < 0.05). In addition, the fermented back gluten has higher free radical scavenging activity and iron reduction capacity. Therefore, fermented gluten may be used as a functional food to alleviate oxidative stress. This study provides a reference for the high-value application of gluten.