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Laccase is capable of catalyzing a vast array of reactions, but its low redox potential limits its potential applications. The use of photocatalytic materials offers a solution to this problem by converting absorbed visible light into electrons to facilitate enzyme catalysis. Herein, MIL-53(Fe) and NH2-MIL-53(Fe) serve as both light absorbers and enzyme immobilization carriers, and laccase is employed for solar-driven chemical conversion. Electron spin resonance spectroscopy results confirm that visible light irradiation causes rapid transfer of photogenerated electrons from MOF excitation to T1 Cu(II) of laccase, significantly increasing the degradation rate constant of tetracycline (TC) from 0.0062 to 0.0127 min-1. Conversely, there is only minimal or no electron transfer between MOF and laccase in the physical mixture state. Theoretical calculations demonstrate that the immobilization of laccase's active site and its covalent binding to the metal-organic framework surface augment the coupled system's activity, reducing the active site accessible from 27.8 to 18.1 Å. The constructed photo-enzyme coupled system successfully combines enzyme catalysis' selectivity with photocatalysis's high reactivity, providing a promising solution for solar energy use.
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Interferon-inducible transmembrane protein 3 (IFITM3), a member of the interferon-stimulating factor (ISG) family, has various antiviral functions. Infectious bursal disease virus (IBDV) mainly invades the bursa of Fabricius in chickens, causing a reduction in their immunity and resulting in death from secondary infections. Our previous study found that IBDV infection promotes the expression of chicken IFITM3. However, the role of chicken IFITM3 in IBDV infection remains unknown. To explore this role, the overexpression vector for IFITM3 was constructed and transfected into HD-11 and DF-1 cells. The results showed that the overexpression of IFITM3 significantly reduced IBDV proliferation. While the IBDV proliferation increased when IFITM3 was inhibited by using siRNA. To further explore the mechanism by which IFITM3 reduces IBDV proliferation, the effects of IFITM3 on interferon (IFN) were investigated. Transfecting the constructed IFITM3 vectors into HD-11 and DF-1 cells demonstrated that IFITM3 promoted the expression of IFN-α, IFN-ß, and IFN-γ. To investigate the mechanism by which IFITM3 regulates IFN expression, the effects of IFITM3 on IFN production were explored. The results showed that the IKB gene mainly affected the regulatory effects of IFITM3 on IFN. Taken together, IFITM3 may reduce viral proliferation by regulating changes in IFNs, and this process may involve a positive feedback effect of IFITM3 on IFN. IKB plays an important role in the regulation of IFN effects by IFITM3.
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BACKGROUND: Drug resistance poses a significant challenge in cancer treatment, particularly as a leading cause of therapy failure. Cisplatin, the primary drug for lung adenocarcinoma (LUAD) chemotherapy, shows effective treatment outcomes. However, the development of resistance against cisplatin is a major obstacle. Therefore, identifying genes resistant to cisplatin and adopting personalized treatment could significantly improve patient outcomes. METHODS: By examining transcriptome data of cisplatin-resistant LUAD cells from the GEO database, 181 genes associated with cisplatin resistance were identified. Using univariate regression analysis, random forest and multivariate regression analyses, two prognostic genes, E2F7 and FAM83A, were identified. This study developed a prognostic model utilizing E2F7 and FAM83A as key indicators. The Cell Counting Kit 8 assay, Transwell assay, and flow cytometry were used to detect the effects of E2F7 on the proliferation, migration, invasiveness and apoptosis of A549/PC9 cells. Western blotting was used to determine the effect of E2F7 on AKT/mTOR signaling pathway. RESULTS: This study has pinpointed two crucial genes associated with cisplatin resistance, E2F7 and FAM83A, and developed a comprehensive model to assist in the diagnosis, prognosis, and evaluation of relapse risk in LUAD. Analysis revealed that patients at higher risk, according to these genetic markers, had elevated levels of immune checkpoints (PD-L1 and PD-L2). The prognostic and diagnosis values of E2F7 and FAM83A were further confirmed in clinical data. Furthermore, inhibiting E2F7 in lung cancer cells markedly reduced their proliferation, migration, invasion, and increased apoptosis. In vivo experiments corroborated these findings, showing reduced tumor growth and lung metastasis upon E2F7 suppression in lung cancer models. CONCLUSION: Our study affirms the prognostic value of a model based on two DEGs, offering a reliable method for predicting the success of tumor immunotherapy in patients with LUAD. The diagnostic and predictive model based on these genes demonstrates excellent performance. In vitro, reducing E2F7 levels shows antitumor effects by blocking LUAD growth and progression. Further investigation into the molecular mechanisms has highlighted E2F7's effect on the AKT/mTOR signaling pathway, underscoring its therapeutic potential. In the era of personalized medicine, this DEG-based model promises to guide clinical practice.
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Polyethylene terephthalate (PET) hydrolase, discovered in Ideonella sakaiensis (IsPETase), is a promising agent for the biodegradation of PET under mild reaction conditions, yet the thermal stability is poor. The efficient immobilization and orientation of IsPETase on different solid substrates are essential for its application. In this work, the combined parallel tempering Monte Carlo simulation with the all-atom molecular dynamics simulation approach was adopted to reveal the adsorption mechanism, orientation, and conformational changes of IsPETase adsorbed on charged self-assembled monolayers (SAMs), including COOH-SAM and NH2-SAM with different surface charge densities (SCDs). The results show that the protein adsorption orientation was determined not only by attraction interactions but also by repulsion interactions. IsPETase is adsorbed on the COOH-SAM surface with an "end-on" orientation, which favors the exposure of the catalyzed triplet to the solution. In addition, the entrance to the catalytic active center is larger on the COOH-SAM surface with a low SCD. This work reveals the controlled orientation and conformational information on IsPETase on charged surfaces at the atomistic level. This study would certainly promote our understanding of the mechanism of IsPETase adsorption and provide theoretical support for the design of substrates for IsPETase immobilization.
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Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects. Herein, we genetically engineered a thermal-responsive murine Ferritin (mHFn) to specifically deliver mitoxantrone (MTO, a chemotherapeutic and photothermal agent) to tumor tissue for the chemotherapy and photothermal combined therapy of colorectal cancer, thanks to the high affinity of mHFn to transferrin receptor that highly expressed on tumor cells. The thermal-sensitive channels on mHFn allowed the effective encapsulation of MTO in vitro and the laser-controlled release of MTO in vivo. Upon irradiation with a 660 nm laser, the raised temperature triggered the opening of the thermal-sensitive channel in mHFn nanocage, resulting in the controlled and rapid release of MTO. Consequently, a significant amount of reactive oxygen species was generated, causing mitochondrial collapse and tumor cell death. The photothermal-sensitive controlled release, low systemic cytotoxicity, and excellent synergistic tumor eradication ability in vivo made mHFn@MTO a promising candidate for chemo-photothermal combination therapy against colorectal cancer.
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Neoplasias Colorrectales , Ferritinas , Rayos Láser , Mitoxantrona , Terapia Fototérmica , Animales , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/tratamiento farmacológico , Ratones , Ferritinas/química , Ferritinas/metabolismo , Terapia Fototérmica/métodos , Humanos , Mitoxantrona/farmacología , Mitoxantrona/química , Mitoxantrona/uso terapéutico , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Antineoplásicos/química , Ratones Desnudos , FemeninoRESUMEN
Arctii Fructus is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is in the Chinese pharmacopoeia. Previous research showed that the total lignans from Arctii Fructus (TLAF) have pharmacological activities related to diabetes. This study evaluated the acute and chronic (26 weeks) toxicities associated with oral daily administration of TLAF in Sprague-Dawley (SD) rats. An acute-toxicity test showed that TLAF caused 10% mortality at 3,000 mg/kg × 2 (6-h interval), with toxic symptoms, such as dyspnea and tonic convulsions, indicating potential neurotoxicity. A chronic-toxicity study showed no mortality after administration. The no observed adverse-effect level was 1,800 mg/kg (approximately 54 times higher than the human clinical dose) for 26 weeks of TLAF oral administration in SD rats, with toxicity signs of excessive oral and nasal secretions and moist circumferential hair that recovered after TLAF discontinuation. In the toxicokinetic study, the two main components of TLAF, arctigenin plasma level was positively correlated with dose and tended to accumulate after multiple doses. At 1,800 mg/kg, arctiin plasma level increased and tended to accumulate after multiple doses. These results indicated that TLFA has relatively low toxicity and the potential for clinical treatment of diabetes.
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Diabetes Mellitus , Medicamentos Herbarios Chinos , Lignanos , Ratas , Humanos , Animales , Ratas Sprague-Dawley , Preparaciones Farmacéuticas , Diabetes Mellitus/tratamiento farmacológico , Lignanos/toxicidadRESUMEN
Five new naphthalene derivatives dalesconosides A-D, F (1-4, 6), a known synthetic analogue named dalesconoside E (5), and eighteen known compounds (7-24) were isolated from Daldinia eschscholzii MCZ-18, which is an endophytic fungus obtained from the Chinese mangrove plant Ceriops tagal. Differing from previously reported naphthalenes, compounds 1 and 2 were bearing a rare ribofuranoside substituted at C-1 and the 5-methyltetrahydrofuran-2,3-diol moiety, respectively. Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analyses, while the absolute configurations were established by theoretical electronic circular dichroism (ECD) calculation. Compounds 1, 3, 13-17 and 19 showed broad ranges of antimicrobial spectrum against five indicator test microorganisms (Enterococcus faecalis, Methicillin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans); especially, 1, 16 and 17 were most potent. The variations in structure and attendant biological activities provided fresh insights concerning structure-activity relationships for the naphthalene derivatives.
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Pruebas de Sensibilidad Microbiana , Naftalenos , Naftalenos/farmacología , Naftalenos/química , Naftalenos/aislamiento & purificación , Relación Estructura-Actividad , Espectroscopía de Resonancia Magnética , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Candida albicans/efectos de los fármacos , Estructura Molecular , Rhizophoraceae/microbiología , Endófitos/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificaciónRESUMEN
Wuzhuyu decoction (WZYD) is a well-known classic traditional Chinese medicine prescription and has been widely used to treat headache, nausea, vomiting, insomnia, etc. However, little published information is available about its safety. Our aim was to investigate the acute and subacute oral toxicity of WZYD extract in rats following the technical guidelines from China's National Medical Products Administration (NMPA) for single and repeated doses toxicity studies of drugs. Acute oral toxicity was assessed in rats via oral administration of WZYD extract at 4 g/kg three times within a day followed by a 14-day observation period. To evaluate the subacute toxicity, rats were orally administered with WZYD extract at doses of 0, 0.44, 1.33, and 4 g/kg for 28 days. The items examined included clinical signs, body weight, food consumption, hematological and biochemical parameters, bone marrow smear, organ index, and histopathology. After the rats were administered with 12 g/kg (3 × 4 g/kg) WZYD extract, no mortality and toxic effects were observed during the observation period. In the subacute toxicity study, WZYD extract did not cause any significant treatment-related abnormality in each examined item of rats, so the no observed adverse effect level (NOAEL) of WZYD extract for 28 days orally administered to rats is considered to be 4 g/kg, which is approximately 80-fold of its clinical proposed dosage.
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Two pairs of cyclohexene amide alkaloid enantiomers were obtained from the root of Piper nigrum. Their plane structures were established by NMR and HRESIMS spectra. The absolute configurations of 1a/1b and 2a/2b were determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. All identified compounds were tested for inhibitory effects on acetylcholinesterase (AChE) in vitro. Notably, compounds 1b and 2b showed strong inhibitory effects on AChE and the interaction between proteins and compounds was discussed by molecular docking studies.
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BACKGROUND: The error magnitude is closely related to patient-specific dosimetry and plays an important role in evaluating the delivery of the radiotherapy plan in QA. No previous study has investigated the feasibility of deep learning to predict error magnitude. OBJECTIVE: The purpose of this study was to predict the error magnitude of different delivery error types in radiotherapy based on ResNet. METHODS: A total of 34 chest cancer plans (172 fields) of intensity-modulated radiation therapy (IMRT) from Eclipse were selected, of which 30 plans (151 fields) were used for model training and validation, and 4 plans including 21 fields were used for external testing. The collimator misalignment (COLL), monitor unit variation (MU), random multi-leaf collimator shift (MLCR), and systematic MLC shift (MLCS) were introduced. These dose distributions of portal dose predictions for the original plans were defined as the reference dose distribution (RDD), while those for the error-introduced plans were defined as the error-introduced dose distribution (EDD). Different inputs were used in the ResNet for predicting the error magnitude. RESULTS: In the test set, the accuracy of error type prediction based on the dose difference, gamma distribution, and RDDâ+âEDD was 98.36%, 98.91%, and 100%, respectively; the root mean squared error (RMSE) was 1.45-1.54, 0.58-0.90, 0.32-0.36, and 0.15-0.24; the mean absolute error (MAE) was 1.06-1.18, 0.32-0.78, 0.25-0.27, and 0.11-0.18, respectively, for COLL, MU, MLCR and MLCS. CONCLUSIONS: In this study, error magnitude prediction models with dose difference, gamma distribution, and RDDâ+âEDD are established based on ResNet. The accurate prediction of the error magnitude under different error types can provide reference for error analysis in patient-specific QA.
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Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Radioterapia de Intensidad Modulada/normas , Garantía de la Calidad de Atención de Salud/normas , Garantía de la Calidad de Atención de Salud/métodos , Radiometría/métodos , Radiometría/normas , Aprendizaje ProfundoRESUMEN
Purpose: This study aims to assess the dosimetry and treatment efficiency of TaiChiB-based Stereotactic Body Radiotherapy (SBRT) plans applying to treat two-lung lesions with one overlapping organs at risk. Methods: For four retrospective patients diagnosed with two-lung lesions each patient, four treatment plans were designed including Plan Edge, TaiChiB linac-based, RGS-based, and a linac-RGS hybrid (Plan TCLinac, Plan TCRGS, and Plan TCHybrid). Dosimetric metrics and beam-on time were employed to evaluate and compare the TaiChiB-based plans against Plan Edge. Results: For Conformity Index (CI), Plan TCRGS outperformed all other plans with an average CI of 1.06, as opposed to Plan Edge's 1.33. Similarly, for R50 %, Plan TCRGS was superior with an average R50 % of 3.79, better than Plan Edge's 4.28. In terms of D2âcm, Plan TCRGS also led with an average of 48.48%, compared to Plan Edge's 56.25%. For organ at risk (OAR) sparing, Plan TCRGS often displayed the lowest dosimetric values, notably for the spinal cord (Dmax 5.92âGy) and lungs (D1500cc 1.00âGy, D1000cc 2.61âGy, V10âGy 15.14%). However, its high Dmax values for the heart and great vessels sometimes exceeded safety thresholds. Plan TCHybrid presented a balanced approach, showing doses comparable to or better than Plan Edge without crossing safety limits. In terms of beam-on time, Plan TCLinac emerged as the most efficient treatment option in three out of four cases, followed closely by Plan Edge in one case. Plan TCRGS, despite its dosimetric advantages, was the least efficient, recording notably longer beam-on times, with a peak at 33.28 minutes in Case 2. Conclusion: For patients with two-lung lesions treated by SBRT whose one lesion overlaps with OARs, the Plan TCHybrid delivered by TaiChiB digital radiotherapy system can be recommended as a clinical option.
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Neoplasias Pulmonares , Radiocirugia , Radioterapia de Intensidad Modulada , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Órganos en Riesgo , Planificación de la Radioterapia Asistida por Computador , Dosificación Radioterapéutica , Pulmón/patología , EtopósidoRESUMEN
The relative research on investigating the association between dietary diversity scores and anthropometric status among young children is few and inconsistent. Since understanding this association is quite essential to give more detailed advice about diet to ensure young children's healthy growth, we sought to determine the association between dietary diversity levels and anthropometric status among young children under 24 months. The study included 1408 mother-child pairs from the Tongji Maternal and Child Health Cohort, whose children range in age from 12 to 24 months. Multivariable logistic regressions were used to examine the effect of dietary diversity on children's anthropometric failure and obesity. All obese children aged 12 and 24 months had low-medium diverse diets in their first year of life. Risks of anthropometric failure for 12-month young children consumed low-medium diverse diets in their first year and 24-month young children consumed low-medium diverse diets in their second year are, respectively, 1.27 (odds ratio [OR], 95% confidence interval [CI] = [1.06-1.53]) and 1.19 (OR, 95% CI = [1.02-1.40]) times of those who consumed high diverse diets in corresponding year. The risk of anthropometric failure for 24-month-old children who consumed low-medium diverse diets during their first year of life is 4.70 (OR, 95% CI = [1.62-19.91]) times that of young children who consumed highly diverse diets during their first year of life. Introducing more diverse diets to young children under 24 months of age may be an effective strategy to prevent anthropometric failure and obesity in young children in later life.
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Obesidad Infantil , Niño , Humanos , Lactante , Preescolar , Obesidad Infantil/epidemiología , Dieta , Antropometría , China/epidemiología , Estado NutricionalRESUMEN
Curvature measurement plays an important role in various applications. An optical curvature sensor based on polarization characteristics of optical fiber is proposed and verified by experiments. The direct bending of the fiber causes a change in birefringence, which results in a change of Stokes parameters of the transmitted light. The large curvature measurement range of tens to more than 100â m-1 has been realized in the experiment. For micro bending, a cantilever beam structure is used to achieve a sensitivity of up to 12.26/ m-1 and a linearity of 99.49% in the measurement range of 0 to 0.15â m-1, with a resolution of up to 10-6â m-1 order of magnitude, which reaches the level of the latest report. The method with the advantages of simple fabrication, low cost and good real-time performance gives a new development direction to the curvature sensor.
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BACKGROUND: Visceral obesity is associated with high cardiovascular events risk in type 2 diabetes mellitus (T2DM). Whether normal-weight visceral obesity will pose a higher atherosclerotic cardiovascular disease (ASCVD) risk than body mass index (BMI)-defined overweight or obese counterparts with or without visceral obesity remains unclear. We aimed to explore the relationship between general obesity and visceral obesity and 10-year ASCVD risk in patients with T2DM. METHODS: Patients with T2DM (6997) who satisfied the requirements for inclusion were enrolled. Patients were considered to have normal weight when 18.5 kg/m2 ≤ BMI < 24 kg/m2; overweight when 24 kg/m2 ≤ BMI < 28 kg/m2; and obesity when BMI ≥ 28 kg/m2. Visceral obesity was defined as a visceral fat area (VFA) ≥ 100 cm2. Patients were separated into six groups based on BMI and VFA. The odd ratios (OR) for a high 10-year ASCVD risk for different combinations of BMI and VFA were analysed using stepwise logistic regression. Receiver operating characteristic (ROC) curves for diagnosing the high 10-year ASCVD risk were constructed, and areas under the ROC curves were estimated. Potential non-linear relationships between VFA levels and high 10-year ASCVD risk were examined using restricted cubic splines (knot = 4). Multilinear regression was used to identify factors affecting VFA in patients with T2DM. RESULTS: In patients with T2DM, subjects with normal-weight visceral obesity had the highest 10-year ASCVD risk among the six groups, which had more than a 2-fold or 3-fold higher OR than those who were overweight or obese according to BMI but did not have visceral obesity (all P < 0.05). The VFA threshold for high 10-year ASCVD risk was 90 cm2. Multilinear regression showed significant differences in the effect of age, hypertension, drinking, fasting serum insulin, fasting plasma glucose, 2 h postprandial C-peptide, triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol on VFA in patients with T2DM (all P < 0.05). CONCLUSIONS: T2DM patients with normal-weight visceral obesity had a higher 10-year ASCVD risk than BMI-defined overweight or obese counterparts with or without visceral obesity, which should initiate standardised management for ASCVD primary prevention.
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Aterosclerosis , Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Obesidad Abdominal , Sobrepeso , Obesidad , China , HDL-ColesterolRESUMEN
OBJECTIVE: This study aimed to improve the image quality and CT Hounsfield unit accuracy of daily cone-beam computed tomography (CBCT) using registration generative adversarial networks (RegGAN) and apply synthetic CT (sCT) images to dose calculations in radiotherapy. METHODS: The CBCT/planning CT images of 150 esophageal cancer patients undergoing radiotherapy were used for training (120 patients) and testing (30 patients). An unsupervised deep-learning method, the 2.5D RegGAN model with an adaptively trained registration network, was proposed, through which sCT images were generated. The quality of deep-learning-generated sCT images was quantitatively compared to the reference deformed CT (dCT) image using mean absolute error (MAE), root mean square error (RMSE) of Hounsfield units (HU), and peak signal-to-noise ratio (PSNR). The dose calculation accuracy was further evaluated for esophageal cancer radiotherapy plans, and the same plans were calculated on dCT, CBCT, and sCT images. RESULTS: The quality of sCT images produced by RegGAN was significantly improved compared to the original CBCT images. ReGAN achieved image quality in the testing patients with MAE sCT vs. CBCT: 43.7⯱ 4.8 vs. 80.1⯱ 9.1; RMSE sCT vs. CBCT: 67.2⯱ 12.4 vs. 124.2⯱ 21.8; and PSNR sCT vs. CBCT: 27.9⯱ 5.6 vs. 21.3⯱ 4.2. The sCT images generated by the RegGAN model showed superior accuracy on dose calculation, with higher gamma passing rates (93.3⯱ 4.4, 90.4⯱ 5.2, and 84.3⯱ 6.6) compared to original CBCT images (89.6⯱ 5.7, 85.7⯱ 6.9, and 72.5⯱ 12.5) under the criteria of 3â¯mm/3%, 2â¯mm/2%, and 1â¯mm/1%, respectively. CONCLUSION: The proposed deep-learning RegGAN model seems promising for generation of high-quality sCT images from stand-alone thoracic CBCT images in an efficient way and thus has the potential to support CBCT-based esophageal cancer adaptive radiotherapy.
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Neoplasias Esofágicas , Tomografía Computarizada de Haz Cónico Espiral , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía Computarizada de Haz Cónico/métodos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/radioterapiaRESUMEN
PURPOSE: The goal of this study was to propose a knowledge-based planning system which could automatically design plans for lung cancer patients treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: From May 2018 to June 2020, 612 IMRT treatment plans of lung cancer patients were retrospectively selected to construct a planning database. Knowledge-based planning (KBP) architecture named αDiar was proposed in this study. It consisted of two parts separated by a firewall. One was the in-hospital workstation, and the other was the search engine in the cloud. Based on our previous study, ANet in the in-hospital workstation was used to generate predicted virtual dose images. A search engine including a three-dimensional convolutional neural network (3D CNN) was constructed to derive the feature vectors of dose images. By comparing the similarity of the features between virtual dose images and the clinical dose images in the database, the most similar feature was found. The optimization parameters (OPs) of the treatment plan corresponding to the most similar feature were assigned to the new plan, and the design of a new treatment plan was automatically completed. After αDiar was developed, we performed two studies. The first retrospective study was conducted to validate whether this architecture was qualified for clinical practice and involved 96 patients. The second comparative study was performed to investigate whether αDiar could assist dosimetrists in improving the quality of planning for the patients. Two dosimetrists were involved and designed plans for only one trial with and without αDiar; 26 patients were involved in this study. RESULTS: The first study showed that about 54% (52/96) of the automatically generated plans would achieve the dosimetric constraints of the Radiation Therapy Oncology Group (RTOG) and about 93% (89/96) of the automatically generated plans would achieve the dosimetric constraints of the National Comprehensive Cancer Network (NCCN). The second study showed that the quality of treatment planning designed by junior dosimetrists was improved with the help of αDiar. CONCLUSIONS: Our results showed that αDiar was an effective tool to improve planning quality. Over half of the patients' plans could be designed automatically. For the remaining patients, although the automatically designed plans did not fully meet the clinical requirements, their quality was also better than that of manual plans.
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OBJECTIVE: To identify delivery error type and predict associated error magnitude by image-based features using machine learning (ML). METHODS: In this study, a total of 40 thoracic plans (including 208 beams) were selected, and four error types with different magnitudes were introduced into the original plans, including 1) collimator misalignment (COLL), 2) monitor unit (MU) variation, 3) systematic multileaf collimator misalignment (MLCS), and 4) random MLC misalignment (MLCR). These dose distributions of portal dose predictions for the original plans were defined as the reference dose distributions (RDD), while those for the error-introduced plans were defined as the error-introduced dose distributions (EDD). Both distributions were calculated for all beams with portal dose image prediction (PDIP). Besides, 14 image-based features were extracted from RDD and EDD of portal dose predictions to obtain the feature vectors. In addition, a random forest was adopted for the multiclass classification task, and regression prediction for error magnitude. RESULTS: The top five features extracted with the highest weight included 1) the relative displacement in the x direction, 2) the ratio of the absolute minimum residual error to the maximal RDD value, 3) the product of the maximum and minimum residuals, 4) the ratio of the absolute maximum residual error to the maximal RDD value, and 5) the ratio of the absolute mean residual value to the maximal RDD value. The relative displacement in the x direction had the highest weight. The overall accuracy of the five-class classification model was 99.85% for the validation set and 99.30% for the testing set. This model could be applied to the classification of the error-free plan, COLL, MU, MLCS, and MLCR with an accuracy of 100%, 98.4%, 99.9%, 98.0%, and 98.3%, respectively. MLCR had the worst performance in error magnitude prediction (70.1-96.6%), while others had better performance in error magnitude prediction (higher than 93%). In the error magnitude prediction, the mean absolute error (MAE) between predicted error magnitude and actual error ranged from 0.03 to 0.33, with the root mean squared error (RMSE) varying from 0.17 to 0.56 for the validation set. The MAE and RMSE ranged from 0.03 to 0.50 and 0.44 to 0.59 for the test set, respectively. CONCLUSION: It could be demonstrated in this study that the image-based features extracted from RDD and EDD can be employed to identify different types of delivery errors and accurately predict error magnitude with the assistance of ML techniques. They can be used to associate traditional gamma analysis with clinically based analysis for error classification and magnitude prediction in patient-specific IMRT quality assurance.
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Radioterapia de Intensidad Modulada , Humanos , Radioterapia de Intensidad Modulada/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Aprendizaje Automático , Dosificación RadioterapéuticaRESUMEN
Cellobiose dehydrogenase (CDH) is capable of direct electron transfer (DET) on electrodes and is a promising redox enzyme for bioelectrochemical applications. Its unique two-domain structure makes the function of CDH adsorbed on the surface of the electrode deeply affected by the external environment, such as ion species, strength, pH, and surface charge density. To date, however, the exact mechanism of how the external environment tailors the structure and dynamics of CDH adsorbed on the electrode surface still remains poorly understood. Here, multiscale simulations were performed to look for insight into the effect of Na+ and Ca2+ ions on the activation of CDH on oppositely charged self-assembled monolayer (NH2-SAM and COOH-SAM) surfaces with different surface charge densities (SCDs). Both Na+ and Ca2+ can promote CDH conformation switch from the open state to the closed state, while the promotion effect of Ca2+ is stronger than that of Na+ at the same conditions. However, the high ionic strength (IS) of Ca2+ renders the cytochrome (CYT) domain of CDH away from the NH2-SAM with low SCD. In contrast, whatever the IS, the NH2-SAM surface with high SCD can not only enhance the CYT-surface interaction but also achieve a closed-state conformation due to a similar role of Ca2+. Overall, this study gains molecular-level insights into the role of ion species and surface charge in modulating the structure and conformation of CDH on the SAM surface, thereby tailoring its activity.
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Deshidrogenasas de Carbohidratos , Adsorción , Transporte de Electrón , Oxidación-Reducción , Deshidrogenasas de Carbohidratos/química , Deshidrogenasas de Carbohidratos/metabolismo , ElectrodosRESUMEN
Artemisinin-hydroxychloroquine sulfate tablets (AH) are regarded as a relatively inexpensive and novel combination therapy for the treatment of various forms of malaria, particularly aminoquinoline drugs-resistant strains of Plasmodium falciparum. Our aim was to conduct acute and subacute oral toxicity studies in non-rodents to obtain more nonclinical data on the safety of AH. Acute toxicity evaluation was performed in beagle dogs at single doses of 230, 530, 790, 1180, 2660, and 5000 mg/kg. Beagle dogs at doses of 0, 56, 84, and 126 mg/kg were used to assess subacute toxicity for 14 days. The approximate lethal dose range for acute oral administration of AH in dogs is found to be 790-1180 mg/kg, and toxic symptoms prior to death include gait instability, limb weakness, mental fatigue, tachypnea, and convulsion. Repeated doses of AH in dogs caused vomiting, soft feces, decreased activity, anorexia, and splenic red pulp vacuolation. Of note, AH could reduce body weight gain and prolong the QTc interval of individual dogs. Therefore, the no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) of oral administration of AH for 14 days in dogs are determined to be 84 mg/kg and 126 mg/kg, respectively.
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Artemisininas , Hidroxicloroquina , Perros , Animales , Artemisininas/toxicidad , Nivel sin Efectos Adversos Observados , Administración Oral , ComprimidosRESUMEN
BACKGROUND: Dose to heart substructures is a better predictor for major adverse cardiac events (MACE) than mean heart dose (MHD). We propose an avoidance planning strategy for important cardiac substructures. MATERIAL AND METHODS: Two plans, clinical and cardiac substructure-avoidance plan, were generated for twenty patients. Five dose-sensitive substructures, including left ventricle, pulmonary artery, left anterior descending branch, left circumflex branch and the coronary artery were chosen. The avoidance plan aims to meet the target criteria and organ-at-risk (OARs) constraints while minimizing the dose parameters of the above five substructures. The dosimetric assessments included the mean dose and the maximum dose of cardiac substructures and several volume parameters. In addition, we also evaluated the relative risk of coronary artery disease (CAD), chronic heart failure (CHF), and radiation pneumonia (RP). RESULTS: Pearson correlation coefficient and R2 value of linear regression fitting demonstrated that MHD had poor prediction ability for the mean dose of the cardiac substructures. Compared to clinical plans, an avoidance plan is able to statistically significantly decrease the dose to key substructures. Meanwhile, the dose to OARs and the coverage of the target are comparable in the two plans. In addition, it can be observed that the avoidance plan statistically decreases the relative risks of CAD, CHF, and RP. CONCLUSIONS: The substructure-avoidance planning strategy that incorporates the cardiac substructures into optimization process, can protect the important heart substructures, such as left ventricle, left anterior descending branch and pulmonary artery, achieving the substantive sparing of dose-sensitive cardiac structures, and have the potential to decrease the relative risks of CAD, CHF, and RP.