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BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1â2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.
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Theory and experiment have revealed that spin-orbit coupling (SOC) strongly depends on the relativistic effect in topological insulators (TIs), while the influence of orbitals is always ignored. Herein, we provide a direct way of controlling effective SOC with the help of orbital effects, reducing the dependence on elements. Taking 5d W2CO2 and 4d Mo2CO2 MXenes as a specific example, we predict that by decreasing the hybridization strength of W atoms with C or O atoms in 2D W2CO2, the nontrivial bandgaps at the Γ-point are directly enhanced. The weak hybridization of W atoms with ligand elements enhances the electron localization of degenerate d-orbitals of three groups under the triangular prism crystal field, inducing stronger on-site Coulomb repulsion that enhances orbital polarization as well as boosts the SOC effect. Meanwhile, similar results have also been observed in 4d Mo2CO2. This implies that the orbital effects are an efficient and straightforward way to control the nontrivial bandgap in 2D MXene TIs. Our work not only provides an alternative perspective on designing large nontrivial bandgaps but also brings a possibility to control the SOC effect for TI devices.
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Radionuclides internal radiotherapy (RIT) is a clinically powerful method for cancer treatment, but still poses unsatisfactory therapeutic outcomes due to the hypoxic characteristic of tumor microenvironment (TME). Catalase (CAT) or CAT-like nanomaterials can be used to enzymatically decompose TME endogenous H2O2 to boost TME oxygenation and thus alleviate the hypoxic level within tumors, but their effectiveness is still hindered by the short-lasting of hypoxia relief owing to their poor stability or degradability, thereby failing to match the long therapeutic duration of RIT. Herein, we proposed an innovative strategy of using facet-dependent CAT-like Pd-based two-dimensional (2D) nanoplatforms to continuously enhance RIT. Specifically, rationally designed 2D Pd@Au nanosheets (NSs) enable consistent enzymatic conversion of endogenous H2O2 into O2 to overcome hypoxia-induced RIT resistance. Furthermore, partially coated Au layer afford NIR-II responsiveness and moderate photothermal treatment that augmenting their enzymatic functionality. This approach with dual-effect paves the way for reshaping TME and consequently facilitating the brachytherapy ablation of cancer. Our work offers a significant advancement in the integration of catalytic nanomedicine and nuclear medicine, with the overarching goal of amplifying the clinical benefits of RIT-treated patients.
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Nanopartículas , Neoplasias , Humanos , Peróxido de Hidrogênio , Microambiente Tumoral , Hipóxia/tratamento farmacológico , Catálise , Nanomedicina , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Neoplasias/radioterapiaRESUMO
Orychophragmus violaceus (L.) O. E. Schulz (Brassicaceae) is widely distributed and plentiful in China and has been widely used for its application in ornamental, oil, ecology, foraging, and food. Recent studies have revealed that the main components of Orychophragmus violaceus include flavonoids, alkaloids, phenylpropanoids, phenolic acids, terpenoids, etc., which have pharmacological activities such as antioxidation, antiradiation, antitumor, hepatic protection, antiferroptosis, anti-inflammatory, and antibacterial. In this paper, the nutritional value, chemical compositions, pharmacological activity, and application value of Orychophragmus violaceus are summarized by referring to the relevant domestic and international literature to provide a reference for further research, development, and utilization of Orychophragmus violaceus in the future.
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Alcaloides , Brassicaceae , Brassicaceae/química , Alimentos , Fígado , Valor NutritivoRESUMO
Keratin has the potential to function as the gel matrix in an ophthalmic formulation for the encapsulation of the macrolide antibiotic azithromycin. The quality of this formulation was thoroughly evaluated through various analyses, such as in vitro release assessment, rheological examination, intraocular retention studies in rabbits, assessment of bacteriostatic efficacy, and safety evaluations. It is worth mentioning that the gel demonstrated shear thinning properties and exhibited characteristics of an elastic solid, thereby confirming its structural stability. The gel demonstrated a notable affinity for mucosal surfaces in comparison to traditional azithromycin aqueous solutions. In vitro release testing revealed that drug release transpired via diffusion mechanisms, following a first-order kinetic release pattern. Additionally, the formulated gel exhibited remarkable antibacterial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa in bacteriostatic evaluations. Lastly, safety assessments confirmed that the gel eye drops induced minimal irritation and displayed no apparent cytotoxicity, indicating their good safety and biocompatibility for ocular application. Thus, these findings indicated that the prepared azithromycin gel eye drops complied with the requisite standards for ophthalmic preparations.
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Conjuntivite Bacteriana , Sistemas de Liberação de Medicamentos , Animais , Coelhos , Azitromicina/farmacologia , Queratinas/uso terapêutico , Conjuntivite Bacteriana/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Géis/química , Soluções Oftálmicas/químicaRESUMO
PURPOSE: To evaluate the capabilities and incapabilities of a GPT-4V(ision)-based chatbot in interpreting ocular multimodal images. METHODS: We developed a digital ophthalmologist app using GPT-4V and evaluated its performance with a dataset (60 images, 60 ophthalmic conditions, 6 modalities) that included slit-lamp, scanning laser ophthalmoscopy, fundus photography of the posterior pole (FPP), optical coherence tomography, fundus fluorescein angiography and ocular ultrasound images. The chatbot was tested with ten open-ended questions per image, covering examination identification, lesion detection, diagnosis and decision support. The responses were manually assessed for accuracy, usability, safety and diagnosis repeatability. Auto-evaluation was performed using sentence similarity and GPT-4-based auto-evaluation. RESULTS: Out of 600 responses, 30.6% were accurate, 21.5% were highly usable and 55.6% were deemed as no harm. GPT-4V performed best with slit-lamp images, with 42.0%, 38.5% and 68.5% of the responses being accurate, highly usable and no harm, respectively. However, its performance was weaker in FPP images, with only 13.7%, 3.7% and 38.5% in the same categories. GPT-4V correctly identified 95.6% of the imaging modalities and showed varying accuracies in lesion identification (25.6%), diagnosis (16.1%) and decision support (24.0%). The overall repeatability of GPT-4V in diagnosing ocular images was 63.3% (38/60). The overall sentence similarity between responses generated by GPT-4V and human answers is 55.5%, with Spearman correlations of 0.569 for accuracy and 0.576 for usability. CONCLUSION: GPT-4V currently is not yet suitable for clinical decision-making in ophthalmology. Our study serves as a benchmark for enhancing ophthalmic multimodal models.
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Anhydrous hydrogen fluoride (AHF), a critical raw material for industries such as aluminum, pharmaceuticals, and petroleum, has traditionally been sourced from fluorite-a non-renewable mineral. The unsustainable reliance on fluorite has catalyzed the search for alternative AHF production methods. A promising substitute is fluorosilicic acid (FSA), a byproduct of the phosphate fertilizer industry previously deemed waste. Transforming fluorosilicic acid into AHF not only yields a valuable resource but also addresses the environmental and economic challenges associated with waste management. The innovative practice of producing AHF from fluorosilicic acid signals a shift towards sustainable chemical production by capitalizing on waste, potentially diminishing reliance on fluorite and reducing the industry's environmental impact. This review thoroughly dissects the AHF synthesis process from fluorosilicic acid. Despite the acknowledged importance of fluorinated compounds in numerous industrial applications, research on their synthesis from fluorosilicic acid is limited and fragmented. This review seeks to amalgamate this scattered information by closely scrutinizing diverse industrial processing methods. Additionally, it explores the current and future landscape, economic feasibility, and strategies to navigate the obstacles inherent in synthesizing AHF from fluorosilicic acid. It also assesses the environmental impact of these methods, thereby contributing to the dialogue in this emerging field. The primary aim of this manuscript is to foster further research and promote the industrial uptake of this sustainable process. Highlighting the challenges and proposing potential improvements, the review supports the responsible reuse of waste and advocates for advancements in industrial practices.
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BACKGROUND: Conventional daytime monitoring in a single day may be influenced by factors such as motion artifacts and emotions, and continuous monitoring of nighttime heart rate variability (HRV) and respiration to assist in chronic obstructive pulmonary disease (COPD) diagnosis has not been reported yet. OBJECTIVE: The aim of this study was to explore and compare the effects of continuously monitored HRV, heart rate (HR), and respiration during night sleep on the remote diagnosis of COPD. METHODS: We recruited patients with different severities of COPD and healthy controls between January 2021 and November 2022. Vital signs such as HRV, HR, and respiration were recorded using noncontact bed sensors from 10 PM to 8 AM of the following day, and the recordings of each patient lasted for at least 30 days. We obtained statistical means of HRV, HR, and respiration over time periods of 7, 14, and 30 days by continuous monitoring. Additionally, the effects that the statistical means of HRV, HR, and respiration had on COPD diagnosis were evaluated at different times of recordings. RESULTS: In this study, 146 individuals were enrolled: 37 patients with COPD in the case group and 109 participants in the control group. The median number of continuous night-sleep monitoring days per person was 56.5 (IQR 32.0-113.0) days. Using the features regarding the statistical means of HRV, HR, and respiration over 1, 7, 14, and 30 days, binary logistic regression classification of COPD yielded an accuracy, Youden index, and area under the receiver operating characteristic curve of 0.958, 0.904, and 0.989, respectively. The classification performance for COPD diagnosis was directionally proportional to the monitoring duration of vital signs at night. The importance of the features for diagnosis was determined by the statistical means of respiration, HRV, and HR, which followed the order of respiration > HRV > HR. Specifically, the statistical means of the duration of respiration rate faster than 21 times/min (RRF), high frequency band power of 0.15-0.40 Hz (HF), and respiration rate (RR) were identified as the top 3 most significant features for classification, corresponding to cutoff values of 0.1 minute, 1316.3 nU, and 16.3 times/min, respectively. CONCLUSIONS: Continuous monitoring of nocturnal vital signs has significant potential for the remote diagnosis of COPD. As the duration of night-sleep monitoring increased from 1 to 30 days, the statistical means of HRV, HR, and respiration showed a better reflection of an individual's health condition compared to monitoring the vital signs in a single day or night, and better was the classification performance for COPD diagnosis. Further, the statistical means of RRF, HF, and RR are crucial features for diagnosing COPD, demonstrating the importance of monitoring HRV and respiration during night sleep.
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Frequência Cardíaca , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Masculino , Feminino , Frequência Cardíaca/fisiologia , Estudos Prospectivos , Idoso , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação , Respiração , Taxa Respiratória/fisiologiaRESUMO
BACKGROUND: Indocyanine green angiography (ICGA) is vital for diagnosing chorioretinal diseases, but its interpretation and patient communication require extensive expertise and time-consuming efforts. We aim to develop a bilingual ICGA report generation and question-answering (QA) system. METHODS: Our dataset comprised 213 129 ICGA images from 2919 participants. The system comprised two stages: image-text alignment for report generation by a multimodal transformer architecture, and large language model (LLM)-based QA with ICGA text reports and human-input questions. Performance was assessed using both qualitative metrics (including Bilingual Evaluation Understudy (BLEU), Consensus-based Image Description Evaluation (CIDEr), Recall-Oriented Understudy for Gisting Evaluation-Longest Common Subsequence (ROUGE-L), Semantic Propositional Image Caption Evaluation (SPICE), accuracy, sensitivity, specificity, precision and F1 score) and subjective evaluation by three experienced ophthalmologists using 5-point scales (5 refers to high quality). RESULTS: We produced 8757 ICGA reports covering 39 disease-related conditions after bilingual translation (66.7% English, 33.3% Chinese). The ICGA-GPT model's report generation performance was evaluated with BLEU scores (1-4) of 0.48, 0.44, 0.40 and 0.37; CIDEr of 0.82; ROUGE of 0.41 and SPICE of 0.18. For disease-based metrics, the average specificity, accuracy, precision, sensitivity and F1 score were 0.98, 0.94, 0.70, 0.68 and 0.64, respectively. Assessing the quality of 50 images (100 reports), three ophthalmologists achieved substantial agreement (kappa=0.723 for completeness, kappa=0.738 for accuracy), yielding scores from 3.20 to 3.55. In an interactive QA scenario involving 100 generated answers, the ophthalmologists provided scores of 4.24, 4.22 and 4.10, displaying good consistency (kappa=0.779). CONCLUSION: This pioneering study introduces the ICGA-GPT model for report generation and interactive QA for the first time, underscoring the potential of LLMs in assisting with automated ICGA image interpretation.
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Lignin upgrading to various functional products is promising to realize high-value utilization of low-cost and renewable biomass waste, but is still in its infancy. Herein, using industry waste lignosulfonate as the biomass-based carbon source and urea as the dopant, we constructed a heteroatom-doped porous carbon nanosheet structure by a simple NaCl template-assisted pyrolytic strategy. Through the synergistic effect of the NaCl template and urea, the optimized lignin-derived porous carbon catalyst with high content of active nitrogen species and large specific surface area can be obtained. As a result, the fabricated catalysts exhibited excellent electrocatalytic oxygen reduction activity, as well as good methanol tolerance and stability, comparable to that of commercial Pt/C. Moreover, rechargeable Zn-air batteries assembled with this electrocatalyst have a peak power density of up to 150 mW cm-2 and prominent long-term cycling stability. This study offers an inexpensive and efficient way for the massive production of highly active metal-free catalysts from the plentiful, inexpensive and environmentally friendly lignin, offering a good direction for biomass waste recycling and utilization.
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To external validate the risk assessment model (RAM) of venous thromboembolism (VTE) in multicenter internal medicine inpatients. We prospectively collected 595 internal medical patients (310 with VTE patients, 285 non-VTE patients) were from Beijing Shijitan Hospital, Beijing Chaoyang Hospital, and the respiratory department of Beijing Tsinghua Changgeng Hospital from January 2022 to December 2022 for multicenter external validation. The prediction ability of Caprini RAM, Padua RAM, The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) RAM, and Shijitan (SJT) RAM were compared. This study included a total of 595 internal medicine inpatients, including 242 (40.67%) in the respiratory department, 17 (2.86%) in the respiratory intensive care unit, 49 (8.24%) in the neurology department, 34 (5.71%) in the intensive care unit, 26 (4.37%) in the geriatric department, 22 (3.70%) in the emergency department, 71 (11.93%) in the nephrology department, 63 (10.59%) in the cardiology department, 24 (4.03%) in the hematology department, 6 (1.01%) in the traditional Chinese medicine department, 9 (1.51%) cases in the rheumatology department, 7 (1.18%) in the endocrinology department, 14 (2.35%) in the oncology department, and 11 (1.85%) in the gastroenterology department. Multivariate logistic regression analysis showed that among internal medicine inpatients, age > 60 years old, heart failure, nephrotic syndrome, tumors, history of VTE, and elevated D-dimer were significantly correlated with the occurrence of VTE (P < .05). The incidence of VTE increases with the increase of D-dimer. It was found that the effectiveness of SJT RAM (AUC = 0.80 ± 0.03) was better than Caprini RAM (AUC = 0.74 ± 0.03), Padua RAM (AUC = 0.72 ± 0.03) and IMPROVE RAM (AUC = 0.52 ± 0.03) (P < .05). The sensitivity and Yoden index of SJT RAM were higher than those of Caprini RAM, Pauda RAM, and IMPROVE RAM (P < .05), but specificity was not significantly different between the 4 models (P > .05). The SJT RAM derived from general hospitalized Chinese patients has effective and better predictive ability for internal medicine inpatients at risk of VTE.
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Tromboembolia Venosa , Humanos , Idoso , Pessoa de Meia-Idade , Tromboembolia Venosa/etiologia , Fatores de Risco , Pacientes Internados , Estudos Retrospectivos , Medição de RiscoRESUMO
Background: Type 1 diabetes mellitus (T1DM) is frequently associated with various infections, including mycoses; however, the direct link between T1DM and fungal infections remains under-researched. This study utilizes a Mendelian randomization (MR) approach to investigate the potential causal relationship between T1DM and mycoses. Methods: Genetic variants associated with T1DM were sourced from the European Bioinformatics Institute database, while those related to fungal infections such as candidiasis, pneumocystosis, and aspergillosis were obtained from the Finngen database, focusing on European populations. The primary analysis was conducted using the inverse variance weighted (IVW) method, with additional insight from Mendelian randomization Egger regression (MR-Egger). Extensive sensitivity analyses assessed the robustness, diversity, and potential horizontal pleiotropy of our findings. Multivariable Mendelian randomization (MVMR) was employed to adjust for confounders, using both MVMR-IVW and MVMR-Egger to evaluate heterogeneity and pleiotropy. Results: Genetically, the odds of developing candidiasis increased by 5% in individuals with T1DM, as determined by the IVW method (OR = 1.05; 95% CI 1.02-1.07, p = 0.0001), with a Bonferroni-adjusted p-value of 0.008. Sensitivity analyses indicated no significant issues with heterogeneity or pleiotropy. Adjustments for confounders such as body mass index, glycated hemoglobin levels, and white blood cell counts further supported these findings (OR = 1.08; 95% CI:1.03-1.13, p = 0.0006). Additional adjustments for immune cell counts, including CD4 and CD8 T cells and natural killer cells, also demonstrated significant results (OR = 1.04; 95% CI: 1.02-1.06, p = 0.0002). No causal associations were found between T1DM and other fungal infections like aspergillosis or pneumocystosis. Conclusion: This MR study suggests a genetic predisposition for increased susceptibility to candidiasis in individuals with T1DM. However, no causal links were established between T1DM and other mycoses, including aspergillosis and pneumocystosis.
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Fundus fluorescein angiography (FFA) is a crucial diagnostic tool for chorioretinal diseases, but its interpretation requires significant expertise and time. Prior studies have used Artificial Intelligence (AI)-based systems to assist FFA interpretation, but these systems lack user interaction and comprehensive evaluation by ophthalmologists. Here, we used large language models (LLMs) to develop an automated interpretation pipeline for both report generation and medical question-answering (QA) for FFA images. The pipeline comprises two parts: an image-text alignment module (Bootstrapping Language-Image Pre-training) for report generation and an LLM (Llama 2) for interactive QA. The model was developed using 654,343 FFA images with 9392 reports. It was evaluated both automatically, using language-based and classification-based metrics, and manually by three experienced ophthalmologists. The automatic evaluation of the generated reports demonstrated that the system can generate coherent and comprehensible free-text reports, achieving a BERTScore of 0.70 and F1 scores ranging from 0.64 to 0.82 for detecting top-5 retinal conditions. The manual evaluation revealed acceptable accuracy (68.3%, Kappa 0.746) and completeness (62.3%, Kappa 0.739) of the generated reports. The generated free-form answers were evaluated manually, with the majority meeting the ophthalmologists' criteria (error-free: 70.7%, complete: 84.0%, harmless: 93.7%, satisfied: 65.3%, Kappa: 0.762-0.834). This study introduces an innovative framework that combines multi-modal transformers and LLMs, enhancing ophthalmic image interpretation, and facilitating interactive communications during medical consultation.
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[This corrects the article DOI: 10.3892/etm.2020.8766.].
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Existing automatic analysis of fundus fluorescein angiography (FFA) images faces limitations, including a predetermined set of possible image classifications and being confined to text-based question-answering (QA) approaches. This study aims to address these limitations by developing an end-to-end unified model that utilizes synthetic data to train a visual question-answering model for FFA images. To achieve this, we employed ChatGPT to generate 4,110,581 QA pairs for a large FFA dataset, which encompassed a total of 654,343 FFA images from 9,392 participants. We then fine-tuned the Bootstrapping Language-Image Pre-training (BLIP) framework to enable simultaneous handling of vision and language. The performance of the fine-tuned model (ChatFFA) was thoroughly evaluated through automated and manual assessments, as well as case studies based on an external validation set, demonstrating satisfactory results. In conclusion, our ChatFFA system paves the way for improved efficiency and feasibility in medical imaging analysis by leveraging generative large language models.
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Purpose: To explore the association between the cause of amblyopia and pre-treatment contrast sensitivity, stereoacuity, fixation and nystagmus. Design: Retrospective cohort study. Methods: A retrospective review was conducted for 3408 patients with amblyopia who had not yet started amblyopia treatment utilizing a large amblyopia patient database maintained at Zhongshan Ophthalmic Centre. Six amblyogenic factor subtypes were identified: anisometropia, isoametropia, strabismus, anisometropia and strabismus, monocular visual deprivation, and binocular visual deprivation amblyopia. Monocular best corrected visual acuity (BCVA), the contrast sensitivity function (CSF), fixation, and stereopsis were compared between the subtypes before and after propensity score matching (PSM) for age and sex. Results: The two deprivation groups had poorer BCVA and CSF than the other groups. There were no systematic differences in CSF between the non-deprivation groups. Nystagmus was more common in the bilateral amblyopia groups compared to the monocular amblyopia groups. Eccentric fixation was uncommon with the exception of the anisometropia and strabismus group which had an eccentric fixation rate of 20%. Distance stereoacuity measured without monocular cues was absent for almost all patients. The results were consistent when analyzed using PSM. Conclusion: Visual deprivation causes more severe amblyopia than other amblyogenic factors. For non-deprivation amblyopia subtypes, individual differences such as variation in the severity of the amblyogenic factor might be more important in determining pre-treatment vision than whether amblyopia was caused by refractive error, strabismus or both.
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The development of stable fluorescent sensors for toxic pollutants and drugs is meaningful to the environment and public health. In this work, nitrogen-doped graphene quantum dots (N-GQDs) were facially synthesized by a one-step hydrothermal method using soluble starch and l-arginine as carbon and nitrogen sources in pure water at 190 °C for 4 h. The as-synthesized N-GQDs were well characterized and displayed blue fluorescence emission at 445 nm with excellent pH stability, salt tolerance, thermostability, photobleaching resistance and reproducibility. Moreover, N-GQDs could serve as an "on-off" sensor for selective detection of Cr(vi) and folic acid with low detection limit (0.80 and 2.1 µM), good linear correlation over wide linear range (0-50 µM and 0-200 µM) as well as short response time (<10 s). The practical applications of N-GQDs for Cr(vi) and folic acid detection in actual samples were further investigated and showed acceptable recoveries (92-105%) with relative standard deviations less than 5%. These results indicated that this N-GQDs-based sensor could be a potential alternative for Cr(vi) and folic acid detection in the fields of environmental monitoring and drug analysis.
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Anticancer activity has been extensively studies. In this article, three ligands 2-(6-bromobenzo[d][1,3]dioxol-5-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (BDIP), 2-(7-methoxybenzo[d][1,3]dioxol-5-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (MDIP), 2-(6-nitrobenzo[d][1,3]dioxol-5-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (NDIP) and their iridium(III) complexes: [Ir(ppy)2(BDIP)](PF6) (ppy = deprotonated 2-phenylpyridine, 3a), [Ir(ppy)2(MDIP)](PF6) (3b) and [Ir(ppy)2(NDIP)](PF6) (3c) were synthesized. The cytotoxicity of 3a, 3b, 3c against Huh7, A549, BEL-7402, HepG2, HeLa, and non-cancer NIH3T3 was tested using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The results obtained from the MTT test stated clearly that these complexes demonstrated moderate or non-cytotoxicity toward Huh7, BEL-7402, HepG2 and HeLa except A549 cells. To improve the anticancer efficacy, we used white light to irradiate the mixture of cells and complexes for 30 min, the anticancer activity of the complexes was greatly enhanced. Particularly, 3a and 3b exhibited heightened capability to inhibit A549 cells proliferation with IC50 (half maximal inhibitory concentration) values of 0.7 ± 0.3 µM and 1.8 ± 0.1 µM, respectively. Cellular uptake has shown that 3a and 3b can be accumulated in the cytoplasm. Wound healing and colony forming showed that 3a and 3b significantly hinder the cell migration and growth in the S phase. The complexes open mitochondrial permeability transition pore (MPTP) channel and cause the decrease of membrane potential, release of cytochrome C, activation of caspase 3, and finally lead to apoptosis. In addition, 3a and 3b cause autophagy, increase the lipid peroxidation and lead to ferroptosis. Also, 3a and 3b increase the expression of calreticulin (CRT), high mobility group box 1 (HMGB1), heat shock protein 70 (HSP70), thereby inducing immunogenic cell death.
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Antineoplásicos , Complexos de Coordenação , Irídio , Neoplasias Pulmonares , Irídio/química , Irídio/farmacologia , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Células A549 , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Apoptose/efeitos dos fármacos , Luz , Animais , Camundongos , Proliferação de Células/efeitos dos fármacos , Células NIH 3T3RESUMO
Purpose: Perceptual learning (PL) has shown promising performance in restoring visual function in adolescent amblyopes. We retrospectively compared the effect of a well-accepted PL paradigm on patients with anisometropic amblyopia with or without a patching therapy history (patching therapy [PT] group versus no patching therapy [NPT] group). Methods: Eighteen PT and 13 NPT patients with anisometropic amblyopia underwent monocular PL for 3 months. During training, patients practiced a Gabor detection task following the lateral masking paradigm by applying a temporal two-alternative forced choice procedure with the amblyopic eye. Monocular contrast sensitivity functions (CSF), visual acuity, interocular differences in visual function metrics, and stereoacuity were compared before and after training. Results: PL improved the visual acuity of the amblyopia eyes by 0.5 lines on average in the PT group and 1.5 lines in the NPT group. A significant reduction in the interocular difference in visual acuity was observed in the NPT group (P < 0.01) but not in the PT group (P = 0.05). Regarding CSF metrics, the area under the log CSF and cutoff in the amblyopic eyes of the NPT groups increased after training (P < 0.05). In addition, the interocular differences of the CSF metrics (P < 0.05) in the NPT group were significantly reduced. However, in the PT group, all the CSF metrics were unchanged after training. A total of 27 of 31 patients in both groups had no measurable stereopsis pretraining, and recovery after training was not significant. Conclusions: PL based on a lateral masking training paradigm improved visual function in anisometropic amblyopia. Patients without a patching history achieved greater benefits. Translational Relevance: PL based on a lateral masking training paradigm could be a new treatment for amblyopia.
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Ambliopia , Adolescente , Humanos , Ambliopia/terapia , Estudos Retrospectivos , Olho , Acuidade VisualRESUMO
Xanthoceras sorbifolium Bunge, also known as Tu-Mu-Gua and Wen-Dan-Ge-Zi, has several applications. Clinical data and experimental studies have shown anti-tumor, anti-inflammatory, anti-bacterial, and anti-oxidant properties of Xanthoceras sorbifolium Bunge that inhibits prostate hyperplasia, lowers blood pressure and lipid level, and treats enuresis and urinary incontinence. It also has neuroprotective effects and can treat Alzheimer's disease and Parkinson's syndrome. The research on the chemical composition and pharmacological effects of Xanthoceras sorbifolium Bunge has been increasing. Triterpenoid and triterpenoid saponins are the main constituents in Xanthoceras sorbifolium Bunge and exhibit biological activities. In this review, we summarized the research progress on triterpenoids and their glycosides in Xanthoceras sorbifolia, including the chemical constituents, pharmacological activities, and biogenic pathways of triterpenoid mother nucleus. The results would provide a reference for further research and development of triterpenoids and their glycosides in Xanthoceras sorbifolia.