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1.
Front Pharmacol ; 15: 1251961, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655177

RESUMO

Background: Ticagrelor is a commonly used antiplatelet agent, but due to the stringent criteria for trial population inclusion and the limited sample size, its safety profile has not been fully elucidated. Method: We utilized OpenVigil 2.1 to query the FDA Adverse Event Reporting System database and retrieved reports by the generic name "ticagrelor" published between 1 October 2010 and 31 March 2023. Adverse drug events (ADEs) were classified and described according to the preferred terms and system organ classes in the Medical Dictionary of Regulatory Activity. Proportional reporting ratio (PRR), reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were used to detect signals. Results: The number of ADE reports with ticagrelor as the primary suspect drug was 12,909. The top three ADEs were dyspnea [1824 reports, ROR 7.34, PRR 6.45, information component (IC) 2.68], chest pain (458 reports, ROR 5.43, PRR 5.27, IC 2.39), and vascular stent thrombosis (406 reports, ROR 409.53, PRR 396.68, IC 8.02). The highest ROR, 630.24, was found for "vascular stent occlusion". Cardiac arrest (137 reports, ROR 3.41, PRR 3.39, IC 1.75), atrial fibrillation (99 reports, ROR 2.05, PRR 2.04, IC 1.03), asphyxia (101 reports, ROR 23.60, PRR 23.43, IC 4.51), and rhabdomyolysis (57 reports, ROR 2.75, PRR 2.75, IC 1.45) were suspected new adverse events of ticagrelor. Conclusion: The FAERS database produced potential signals associated with ticagrelor that have not been recorded in the package inserts, such as cardiac arrest, atrial fibrillation, asphyxia, and rhabdomyolysis. Further clinical surveillance is needed to quantify and validate potential hazards associated with ticagrelor-related adverse events.

2.
Small ; : e2311725, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558506

RESUMO

Photocatalytic hydrogen production is a prevalent method for hydrogen synthesis. However, high recombination rate of photogenerated carriers and high activation energy barrier of H remain persistent challenge. Here, the two-step hydrothermal method is utilized to prepare dual S-defect mediated catalyst molybdenum sulfide/zinc indium sulfide (MSv/ZISv), which has high hydrogen production rate of 8.83 mmol g-1h-1 under simulated sunlight. The achieved rate is 21.91 times higher than pure ZnIn2S4 substrate. Defects in ZIS within MSv/ZISv modify the primitive electronic structure by creating defect state that retaining good reducing power, leading to the rapid separation of electron-hole pairs and the generation of additional photogenerated carriers. The internal electric field further enhances the migration toward to cocatalyst. Simultaneously, the defects introduced on the MoS2 cause electron rearrangement, leading to electron clustering on both S vacancies and edge S. Thereby MSv/ZISv exhibits the lowest activation energy barrier and |ΔGH*|. This work explores the division of synergies between different types of S defects, providing new insights into the coupling of defect engineering.

3.
J Immunother ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630910

RESUMO

SUMMARY: Taurine (Tau) has been found to inhibit triple-negative breast cancer (TNBC) invasion and metastasis. However, its effect on tumor-promoting macrophages and tumor suppressor macrophages in breast cancer progression remains unknown. In this study, we investigated the effects of Tau on macrophage polarization and its role in TNBC cell growth, invasion, and metastasis. We induced human THP-1 monocytes to differentiate into M2 macrophages through exogenous addition of interleukin-4. We used the TNBC cell lines MDA-MB-231 and BT-549 cultured in a conditioned medium from M2 macrophages to investigate the effect of Tau on tumor growth and invasion. We analyzed macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression by quantitative polymerase chain reaction. We also detected the PTEN-PI3K/Akt/mTOR signaling pathway that mediates M1 macrophage to suppress tumor invasion using western blotting. Our results showed that Tau inhibits breast cancer metastasis to the lungs in vivo and cell invasion by altering the polarization of tumor-associated macrophage in vitro. In addition, Tau can up-regulate PTEN expression, suppress the PI3K-Akt signaling pathway, and promote the M1 polarization of macrophages, which ultimately inhibits the metastasis of TNBC cells. Our findings suggest that Tau inhibits the activation of the PI3K-Akt-mTOR signaling pathway by up-regulating PTEN, promotes the proportion of M1 macrophages in tumor-associated macrophage, and suppresses the invasion and metastasis of TNBC. This provides a potential therapeutic approach to influence cancer progression and metastasis.

4.
Pharmacol Res ; 202: 107141, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38490314

RESUMO

Osteoarthritis (OA) is a degenerative disease characterised by articular cartilage destruction, and its complex aetiology contributes to suboptimal clinical treatment outcomes. A close association exists between glucose metabolism dysregulation and OA pathogenesis. Owing to the unique environment of low oxygen and glucose concentrations, chondrocytes rely heavily on their glycolytic capacity, exhibiting distinct spatiotemporal differences. However, under pathological stimulation, chondrocytes undergo excessive glycolytic activity while mitochondrial respiration and other branches of glucose metabolism are compromised. This metabolic change induces cartilage degeneration by reprogramming the inflammatory responses. Sirtuins, a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, regulate glucose metabolism in response to energy fluctuations in different cellular compartments,alleviating metabolic stress. SIRT1, the most extensively studied sirtuin, participates in maintaining glucose homeostasis in almost all key metabolic tissues. While actively contributing to the OA progression and displaying diverse biological effects in cartilage protection, SIRT1's role in regulating glucose metabolism in chondrocytes has not received sufficient attention. This review focuses on discussing the beneficial role of SIRT1 in OA progression from a metabolic regulation perspective based on elucidating the primary characteristics of chondrocyte glucose metabolism. We also summarise the potential mechanisms and therapeutic strategies targeting SIRT1 in chondrocytes to guide clinical practice and explore novel therapeutic directions.


Assuntos
Glucose , Osteoartrite , Sirtuína 1 , Animais , Humanos , Cartilagem Articular/patologia , Glucose/metabolismo , Osteoartrite/metabolismo , Sirtuína 1/metabolismo , Sirtuínas/metabolismo
5.
Biomater Sci ; 12(8): 2033-2040, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38517138

RESUMO

Shape memory polymers (SMPs), which initiate shape transformation in response to environmental stimuli, have attracted significant attention in both academic research and technological innovation. The combination of functional nanomaterials and SMPs has led to the emergence of a variety of shape memory polymeric nanocomposites (SMPNs) with multifunctional properties. This has injected new vitality and vigor into fields such as tissue engineering, biomedicine, optical sensing, aerospace and mechanical engineering. In this review article, we present a brief introduction to the fundamentals of SMPs and SMPNs, followed by a discussion of the recent advances in their multifunctional applications in biomedical manufacturing, drug delivery devices, mechanical sensing, micro-engines, etc. The opportunities and challenges in the future development of SMPs are also discussed.


Assuntos
Nanocompostos , Polímeros , Engenharia Tecidual , Sistemas de Liberação de Medicamentos
6.
ACS Nano ; 18(11): 7796-7824, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38456414

RESUMO

Sodium-ion batteries (SIBs) are considered as an alternative to and even replacement of lithium-ion batteries in the near future in order to address the energy crisis and scarcity of lithium resources due to the wide distribution and abundance of sodium resources on the earth. The exploration and development of high-performance anode materials are critical to the practical applications of advanced SIBs. Among various anode materials, bimetallic oxides (BMOs) have attracted special research attention because of their abundance, easy access, rich redox reactions, enhanced capacity and satisfactory cycling stability. Although many BMO anode materials have been reported as anode materials in SIBs, very limited studies summarized the progress and prospect of BMOs in practical applications of SIBs. In this review, recent progress and challenges of BMO anode materials for SIBs have been comprehensively summarized and discussed. First, the preparation methods and sodium storage mechanisms of BMOs are discussed. Then, the challenges, optimization strategies, and sodium storage performance of BMO anode materials have been reviewed and summarized. Finally, the prospects and future research directions of BMOs in SIBs have been proposed. This review aims to provide insight into the efficient design and optimization of BMO anode materials for high-performance SIBs.

7.
J Transl Med ; 22(1): 282, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491529

RESUMO

BACKGROUND: Oral inflammatory diseases are localized infectious diseases primarily caused by oral pathogens with the potential for serious systemic complications. However, publicly available datasets for these diseases are underutilized. To address this issue, a web tool called OralExplorer was developed. This tool integrates the available data and provides comprehensive online bioinformatic analysis. METHODS: Human oral inflammatory disease-related datasets were obtained from the GEO database and normalized using a standardized process. Transcriptome data were then subjected to differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis, and visualization. The single-cell sequencing data was visualized as cluster plot, feature plot, and heatmaps. The web platform was primarily built using Shiny. The biomarkers identified in OralExplorer were validated using local clinical samples through qPCR and IHC. RESULTS: A total of 35 human oral inflammatory disease-related datasets, covering 6 main disease types and 901 samples, were included in the study to identify potential molecular signatures of the mechanisms of oral diseases. OralExplorer consists of 5 main analysis modules (differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis and single-cell analysis), with multiple visualization options. The platform offers a simple and intuitive interface, high-quality images for visualization, and detailed analysis results tables for easy access by users. Six markers (IL1ß, SRGN, CXCR1, FGR, ARHGEF2, and PTAFR) were identified by OralExplorer. qPCR- and IHC-based experimental validation showed significantly higher levels of these genes in the periodontitis group. CONCLUSIONS: OralExplorer is a comprehensive analytical platform for oral inflammatory diseases. It allows users to interactively explore the molecular mechanisms underlying the action and regression of these diseases. It also aids dental researchers in unlocking the potential value of transcriptomics data related to oral diseases. OralExplorer can be accessed at https://smuonco.shinyapps.io/OralExplorer/  (Alternate URL: http://robinl-lab.com/OralExplorer ).


Assuntos
Biologia Computacional , Software , Humanos , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Transcriptoma/genética , Bases de Dados Factuais , Fatores de Troca de Nucleotídeo Guanina Rho
8.
Int Immunopharmacol ; 128: 111418, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38176341

RESUMO

Periodontitis, an inflammatory disease, can cause significant damage to the oral tissues which support the teeth. During the early development of periodontitis, periodontal ligament fibroblasts (PDLFs) undergo metabolic reprogramming regulated by hypoxia-inducible factor 1α (HIF-1α), which is strongly linked to the progression of inflammation. However, the precise mechanisms by which PDLFs regulate HIF-1α and its associated metabolic reprogramming during early inflammation remain unclear. This study illustrated that brief and low-dose exposure to Escherichia coli (E. coli) lipopolysaccharide (LPS) can serve as a non-hypoxic stimulus, effectively replicating early periodontal inflammatory reactions. This is evidenced by the upregulation of HIF-1α expression and the activation of HIF-1α-mediated crucial glycolytic enzymes, namely lactate dehydrogenase a, pyruvate kinase, and hexokinase 2, concomitant with an augmentation in the inflammatory response within PDLFs. We observed that the effects mentioned and their impact on macrophage polarization were notably attenuated when intracellular and extracellular stores of Ca2+ were depleted using BAPTA-AM and Ca2+-free medium, respectively. Mechanistically, our findings demonstrated that the transcriptional process of HIF-1α is regulated by Ca2+ during E. coli LPS stimulation, mediated through the signal transducer and activator of transcription 3 (STAT3) pathway. Additionally, we observed that the stabilization of intracellular HIF-1α proteins occurs via the endothelin (ET)-1-endothelin A receptor pathway, independent of hypoxia. Taken together, our research outcomes underscore the pivotal involvement of Ca2+ in the onset of early periodontitis by modulating HIF-1α and glycolysis, thereby presenting novel avenues for early therapeutic interventions.


Assuntos
Lipopolissacarídeos , Periodontite , Humanos , Lipopolissacarídeos/farmacologia , Escherichia coli/metabolismo , Ligamento Periodontal , Sinalização do Cálcio , Hipóxia/metabolismo , Periodontite/metabolismo , Hipóxia Celular , Inflamação/metabolismo , Fibroblastos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
9.
Biosci Biotechnol Biochem ; 88(4): 405-411, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38271604

RESUMO

Cathepsin L (CTSL) could cleave and activate SARS-CoV-2 Spike protein to promote viral entry, making it a hopeful therapeutic target for COVID-19 prevention and treatment. So CTSL inhibitors are considered to be a promising strategy to SARS-CoV-2 infection. CTSL has previously been expressed in inclusion body in Escherichia coli. In order to prepare CTSL with high purity and activity in soluble active form, we transformed HEK-293T cells with a recombinant mammalian expression plasmid. CTSL was purified to a purity about 95%, found to migrate at approximately 43 kDa and exhibited substrate specificity against Z-Phe-Arg-AMC with specific activity of no less than 85 081 U/mg, characteristic of active CTSL. Although eukaryotic purified CTSL is commercially available, our study for the first time reported the details of the expression, purification, and characterization of active, recombinant CTSL in eukaryocyte system, which laid an experimental foundation for the establishment of high-throughput screening model for anti-coronavirus drugs targeting CTSL.


Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Animais , Humanos , Catepsina L/metabolismo , Mamíferos/metabolismo
10.
Appl Environ Microbiol ; 90(2): e0177923, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38193673

RESUMO

The Pseudoalteromonas genus marine bacteria have attracted increasing interest because of their abilities to produce bioactive metabolites. The pigmented Pseudoalteromonas group encodes more secondary metabolite biosynthetic gene clusters (BGCs) than the non-pigmented group. Here, we report a yellow pigmented bacterium Pseudoalteromonas sp. strain T1lg65, which was isolated from a mangrove forest sediment. We showed that the yellow pigments of T1lg65 belong to the group of lipopeptide alterochromides. Further genetic analyses of the alterochromide BGC revealed that the yellow pigments are biosynthesized by aryl-polyene synthases and nonribosomal peptide synthases. Within the gene cluster, altA encodes a tyrosine ammonia acid lyase, which catalyzes synthesis of the precursor 4-hydroxycinnamic acid (4-HCA) from tyrosine in the alterochromide biosynthetic pathway. In addition, altN, encoding a putative flavin-dependent halogenase, was proven to be responsible for the bromination of alterochromides based on gene deletion, molecular docking, and site mutagenesis analyses. In summary, the biosynthetic pathway, precursor synthesis, and bromination mechanism of the lipopeptide alterochromides were studied in-depth. Our results expand the knowledge on biosynthesis of Pseudoalteromonas pigments and could promote the development of active pigments in the future.IMPORTANCEThe marine bacteria Pseudoalteromonas spp. are important biological resources because they are producers of bioactive natural products, including antibiotics, pigments, enzymes, and antimicrobial peptides. One group of the microbial pigments, alterochromides, holds a great value for their novel lipopeptide structures and antimicrobial activities. Previous studies were limited to the structural characterization of alterochromides and genome mining for the alterochromide biosynthesis. This work focused on the biosynthetic mechanism for alterochromide production, especially revealing functions of two key genes within the gene cluster for the alterochromide biosynthesis. On the one hand, our study provides a target for metabolic engineering of the alterochromide biosynthesis; on the other hand, the 4-HCA synthase AltA and brominase AltN show potential in the biocatalyst industry.


Assuntos
Pseudoalteromonas , Pseudoalteromonas/genética , Pseudoalteromonas/metabolismo , Simulação de Acoplamento Molecular , Flavinas/metabolismo , Lipopeptídeos/metabolismo , Tirosina/metabolismo
11.
Carbohydr Polym ; 329: 121777, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38286548

RESUMO

Developing high-performance microwave absorption (MA) materials becomes an urgent concern in the field of electromagnetic protection. Constructing porous framework is an efficient approach to MA owing to the abilities of adjusting impedance matching and providing more reflection and scattering paths for electromagnetic waves. Herein, a cellulose nanofibril (CNF)/honeycomb-like carbon-shell encapsulated FeCoNi@C/carbon nanotube (CNT) composite aerogel was fabricated via a facile freeze-drying method. The super-lightweight composites showed a distinctive gradient structure for reflection and scattering inside aerogel pores, micrometer small pores, and nano-fillers on the pore walls. The composite aerogel showed an ideal minimum reflection loss (RLmin) of -43.6 dB and remarkable adjustable effective absorption bandwidth (EAB) of 12.18 GHz due to good impedance matching, unique gradient porous structure, and synergies of multiple loss mechanisms. Therefore, this work will provide a viable strategy to improve the MA capability of absorbers by taking full advantage of constructing gradient reflection and scattering porous structure.

12.
Appl Opt ; 63(1): 239-248, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38175026

RESUMO

Elliptical Gaussian beams generated by laser diodes (LDs) often exhibit asymmetrical divergence angle distribution, which limits their practical applications. In this study, we propose what we believe is a novel approach to shape and collimate the elliptical output beam from a LD. The design process involves the construction of two freeform reflective surfaces on a reference circle using a three-dimensional point-by-point iterative method, based on the law of conservation of energy, the vector reflection theory, and Fermat's principle. The output beam's maximum divergence angle is effectively compressed to 3.1579 mrad. The design is compact with a folded optical path and antenna size of 368.8c m 3. This paper presents a comprehensive design and optimization process, along with an in-depth analysis of the system's performance, thereby offering novel insights for emerging optical design practitioners.

13.
Nutrients ; 16(1)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38201995

RESUMO

In recent years, Artocarpus heterophyllus Lam. (jackfruit) polysaccharides (namely JFP-Ps) have attracted much attention due to their multiple biological activities. This study aimed to explore the protective effects and the underlying mechanisms of JFP-Ps on cyclophosphamide (Cp)-induced liver damage. The protective effect of JFP-Ps was evaluated using HE staining, antioxidant testing, enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (RT-qPCR), Western blot and ultra-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) metabolomics analysis. The results showed that Cp caused pathological liver damage, activated oxidative stress and downregulated cytokine expression, while JFP-Ps treatment was found to exert antioxidant effects and play immune regulatory roles through mitogen-activated protein kinase/nuclear factor-κB (MAPK/NF-κB) related inflammation and cell apoptosis pathways to protect the Cp-induced liver injury. Metabolomic results showed that the liver-protective effects of JFP-Ps were mainly related to aminoacyl transfer ribonucleic acid (tRNA) biosynthesis, sphingolipid metabolism, purine metabolism and the citrate cycle. These results indicate that JFP-Ps have great potential application in alleviating liver injury.


Assuntos
Artocarpus , Animais , Camundongos , Espectrometria de Massas em Tandem , Fígado , Polissacarídeos/farmacologia , Antioxidantes/farmacologia , Ciclofosfamida/toxicidade
14.
Adv Mater ; 36(6): e2307855, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37897435

RESUMO

Perovskite solar cells (PSCs) are promising candidates for next-generation photovoltaics owing to their unparalleled power conversion efficiencies (PCEs). Currently, approaches to further improve device efficiencies tend to focus on the passivation of interfacial defects. Although various strategies have been developed to mitigate these defects, many involve complex and time-consuming post-treatment processes, thereby hindering their widespread adoption in commercial applications. In this work, a concise but efficient in situ dual-interface passivation strategy is developed wherein 1-butyl-3-methylimidazolium methanesulfonate (MS) is employed as a precursor additive. During perovskite crystallization, MS can either be enriched downward through precipitation with SnO2 , or can be aggregated upward through lattice extrusion. These self-assembled MS species play a significant role in passivating the defect interfaces, thereby reducing nonradiative recombination losses, and promoting more efficient charge extraction. As a result, a PCE >25% (certified PCE of 24.84%) is achieved with substantially improved long-term storage and photothermal stabilities. This strategy provides valuable insights into interfacial passivation and holds promise for the industrialization of PSCs.

15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(9): 1304-1315, 2023.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38044641

RESUMO

OBJECTIVES: Tubal factor infertility severely impairs the natural fertility of women, and there is for genuine tubal recanalization, including restoration of both the anatomy and function of the diseased fallopian tubes. Currently, there is no effective treatment available. This study aims to explore methods for promoting the repair and recanalization of fallopian tubes from these 2 aspects. METHODS: Apelin-13 sustained-release microspheres and poly (lactic-co-glycolic acid) (PLGA) three-dimensional (3D) biodegradable scaffolds were prepared. The basic characteristics and in vivo degradation (mass loss rate) of the biodegradable scaffolds were tested, along with the in vitro drug release (cumulative release rate), the in vivo drug release (Apelin-13 plasma concentration), and in vitro degradation (degradation rate) of the microspheres. The Apelin-13 microspheres (microsphere group)/PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres (scaffold-microcapsule group) were injected/placed into the fallopian tubes of New Zealand rabbit of chronic salpingitis models. The patency, microscopic structure, and positive expression of estrogen receptor and progesterone receptor of the fallopian tubes in the control group, the model group, the microcapsule group, and the scaffold-microcapsule group was observed and compared. RESULTS: At the 4th week post-operation, the mass loss rate of the PLGA 3D scaffolds, the degradation rate of the microspheres, and the Apelin-13 sustained-release microspheres-generated cumulative release rate in vitro over 30 days were 98.66%, 70.58%, and 98.68% respectively. The plasma concentration of Apelin-13 reached its peak within 5 days and remained stable for 25 days. Compared with the model and microsphere groups, the scaffold-microsphere group showed a milder inflammatory reaction within the tubal lumen, a higher rate of fallopian tube patency, and higher expression levels of estrogen and progesterone receptors (all P<0.05). The indicators of the scaffold-microsphere group were close to those of the control group. CONCLUSIONS: The PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres can comprehensively repair the anatomical structure and physiological function of the fallopian tubes and hold promise for truly effective tubal recanalization.


Assuntos
Ácido Láctico , Ácido Poliglicólico , Coelhos , Feminino , Humanos , Animais , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ácido Poliglicólico/química , Preparações de Ação Retardada , Tubas Uterinas , Cápsulas
16.
Int J Mol Sci ; 24(23)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38069349

RESUMO

Candida albicans (C. albicans), the most common fungal pathogen, has the ability to form a biofilm, leading to enhanced virulence and antibiotic resistance. Cocultimycin A, a novel antifungal antibiotic isolated from the co-culture of two marine fungi, exhibited a potent inhibitory effect on planktonic C. albicans cells. This study aimed to evaluate the anti-biofilm activity of cocultimycin A against C. albicans and explore its underlying mechanism. Crystal violet staining showed that cocultimycin A remarkably inhibited biofilm formation in a dose-dependent manner and disrupted mature biofilms at higher concentrations. However, the metabolic activity of mature biofilms treated with lower concentrations of cocultimycin A significantly decreased when using the XTT reduction method. Cocultimycin A could inhibit yeast-to-hypha transition and mycelium formation of C. albicans colonies, which was observed through the use of a light microscope. Scanning electron microscopy revealed that biofilms treated with cocultimycin A were disrupted, yeast cells increased, and hypha cells decreased and significantly shortened. The adhesive ability of C. albicans cells treated with cocultimycin A to the medium and HOEC cells significantly decreased. Through the use of a qRT-PCR assay, the expression of multiple genes related to adhesion, hyphal formation and cell membrane changes in relation to biofilm cells treated with cocultimycin A. All these results suggested that cocultimycin A may be considered a potential novel molecule for treating and preventing biofilm-related C. albicans infections.


Assuntos
Candida albicans , Candidíase , Antifúngicos/farmacologia , Antifúngicos/química , Candidíase/microbiologia , Violeta Genciana/farmacologia , Biofilmes
17.
JMIR Form Res ; 7: e51921, 2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38145475

RESUMO

BACKGROUND: Medication errors, including dispensing errors, represent a substantial worldwide health risk with significant implications in terms of morbidity, mortality, and financial costs. Although pharmacists use methods like barcode scanning and double-checking for dispensing verification, these measures exhibit limitations. The application of artificial intelligence (AI) in pharmacy verification emerges as a potential solution, offering precision, rapid data analysis, and the ability to recognize medications through computer vision. For AI to be embraced, it must be designed with the end user in mind, fostering trust, clear communication, and seamless collaboration between AI and pharmacists. OBJECTIVE: This study aimed to gather pharmacists' feedback in a focus group setting to help inform the initial design of the user interface and iterative designs of the AI prototype. METHODS: A multidisciplinary research team engaged pharmacists in a 3-stage process to develop a human-centered AI system for medication dispensing verification. To design the AI model, we used a Bayesian neural network that predicts the dispensed pills' National Drug Code (NDC). Discussion scripts regarding how to design the system and feedback in focus groups were collected through audio recordings and professionally transcribed, followed by a content analysis guided by the Systems Engineering Initiative for Patient Safety and Human-Machine Teaming theoretical frameworks. RESULTS: A total of 8 pharmacists participated in 3 rounds of focus groups to identify current challenges in medication dispensing verification, brainstorm solutions, and provide feedback on our AI prototype. Participants considered several teaming scenarios, generally favoring a hybrid teaming model where the AI assists in the verification process and a pharmacist intervenes based on medication risk level and the AI's confidence level. Pharmacists highlighted the need for improving the interpretability of AI systems, such as adding stepwise checkmarks, probability scores, and details about drugs the AI model frequently confuses with the target drug. Pharmacists emphasized the need for simplicity and accessibility. They favored displaying only essential information to prevent overwhelming users with excessive data. Specific design features, such as juxtaposing pill images with their packaging for quick comparisons, were requested. Pharmacists preferred accept, reject, or unsure options. The final prototype interface included (1) checkmarks to compare pill characteristics between the AI-predicted NDC and the prescription's expected NDC, (2) a histogram showing predicted probabilities for the AI-identified NDC, (3) an image of an AI-provided "confused" pill, and (4) an NDC match status (ie, match, unmatched, or unsure). CONCLUSIONS: In partnership with pharmacists, we developed a human-centered AI prototype designed to enhance AI interpretability and foster trust. This initiative emphasized human-machine collaboration and positioned AI as an augmentative tool rather than a replacement. This study highlights the process of designing a human-centered AI for dispensing verification, emphasizing its interpretability, confidence visualization, and collaborative human-machine teaming styles.

18.
Sci Bull (Beijing) ; 68(23): 2945-2953, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37957068

RESUMO

Aqueous proton battery is considered as a promising candidate for the electrochemical energy storage system with the merits of safety, environmental benignity, fast kinetics and low cost. The realization of these advantages relies on the development of suitable and easy-access electrode materials. Herein, micron-sized H2MoO3/Polyaniline (PANI) is developed as a high-rate and stable anode material in proton battery. Contrary to the pseudocapacitive nature of most anode materials, the H2MoO3/PANI presents diffusion-controlled charge storage mechanism with both high capacity and high rate-capability. The H2MoO3/PANI electrode shows a rather high capacity of 268.2 mAh g-1 at 1.0 A g-1, and a surprisingly high rate-capability with ∼50% capacity retention even at an extremely high current density of 200.0 A g-1. Detailed analyses demonstrate the Grotthuss mechanism of ultrafast proton conduction in H2MoO3/PANI. The constructed proton full cell based on H2MoO3/PANI delivers a high energy density of 42.1 Wh kg-1 at 800.0 W kg-1. Impressively, the proton full cell shows fast proton transportation even in the frozen electrolyte, and ∼70% of the room temperature capacity is retained at -20 °C. These excellent proton storage behaviors provide insights into the practical applications of micron-sized electrode materials in proton batteries at low temperatures.

19.
Phys Med Biol ; 68(24)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37918026

RESUMO

Objective.In our previous work on image reconstruction for single-layer collimatorless scintigraphy, we developed the min-min weighted robust least squares (WRLS) optimization algorithm to address the challenge of reconstructing images when both the system matrix and the projection data are uncertain. Whereas the WRLS algorithm has been successful in two-dimensional (2D) reconstruction, expanding it to three-dimensional (3D) reconstruction is difficult since the WRLS optimization problem is neither smooth nor strongly-convex. To overcome these difficulties and achieve robust image reconstruction in the presence of system uncertainties and projection noise, we propose a generalized iterative method based on the maximum likelihood expectation maximization (MLEM) algorithm, hereinafter referred to as the Masked-MLEM algorithm.Approach.In the Masked-MLEM algorithm, only selected subsets ('masks') from the system matrix and the projection contribute to the image update to satisfy the constraints imposed by the system uncertainties. We validate the Masked-MLEM algorithm and compare it to the standard MLEM algorithm using experimental data obtained from both collimated and uncollimated imaging instruments, including parallel-hole collimated SPECT, 2D collimatorless scintigraphy, and 3D collimatorless tomography. Additionally, we conduct comprehensive Monte Carlo simulations for 3D collimatorless tomography to further validate the effectiveness of the Masked-MLEM algorithm in handling different levels of system uncertainties.Main results.The Masked-MLEM and standard MLEM reconstructions are similar in cases with negligible system uncertainties, whereas the Masked-MLEM algorithm outperforms the standard MLEM algorithm when the system matrix is an approximation. Importantly, the Masked-MLEM algorithm ensures reliable image reconstruction across varying levels of system uncertainties.Significance.With a good choice of system uncertainty and without requiring accurate knowledge of the actual system matrix, the Masked-MLEM algorithm yields more robust image reconstruction than the standard MLEM algorithm, effectively reducing the likelihood of erroneously reconstructing higher activities in regions without radioactive sources.


Assuntos
Processamento de Imagem Assistida por Computador , Motivação , Processamento de Imagem Assistida por Computador/métodos , Imagens de Fantasmas , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Algoritmos , Funções Verossimilhança
20.
Heliyon ; 9(11): e21994, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38034639

RESUMO

Three types of Co3O4 catalyst, namely Co3O4 nanoparticles (denoted as Co3O4-NPs, ∼12 nm in diameter), Co3O4 nanoparticles encapsulated in mesoporou s SiO2 (denoted as Co3O4@SiO2), and Co3O4 nanoparticles inside microporous SiO2 hollow sub-microspheres (denoted as Co3O4-in-SiO2), were explored to catalyze the combustion of lean methane. It was found that the methane conversion over the three catalysts has the order of Co3O4-NPs ≈ Co3O4@SiO2 > Co3O4-in-SiO2 due to the different catalyst structure. The comparison experiments at high temperatures indicate the Co3O4@SiO2 has a significantly improved anti-sintering performance. Combined with the TEM and BET measurements, the results prove that the presence of the mesoporous SiO2 layer can maintain the catalytical activity and significantly improve the anti-sintering performance of Co3O4@SiO2. In contrast, the microporous SiO2 layer reduces the catalytical activity of Co3O4-in-SiO2 possibly due to its less effective diffusion path of combustion product. Thus, the paper demonstrates the pore size of SiO2 layer and catalyst structure are both crucial for the catalytical activity and stability.

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