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1.
Cell ; 186(18): 3882-3902.e24, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37597510

RESUMO

Inflammation can trigger lasting phenotypes in immune and non-immune cells. Whether and how human infections and associated inflammation can form innate immune memory in hematopoietic stem and progenitor cells (HSPC) has remained unclear. We found that circulating HSPC, enriched from peripheral blood, captured the diversity of bone marrow HSPC, enabling investigation of their epigenomic reprogramming following coronavirus disease 2019 (COVID-19). Alterations in innate immune phenotypes and epigenetic programs of HSPC persisted for months to 1 year following severe COVID-19 and were associated with distinct transcription factor (TF) activities, altered regulation of inflammatory programs, and durable increases in myelopoiesis. HSPC epigenomic alterations were conveyed, through differentiation, to progeny innate immune cells. Early activity of IL-6 contributed to these persistent phenotypes in human COVID-19 and a mouse coronavirus infection model. Epigenetic reprogramming of HSPC may underlie altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.


Assuntos
COVID-19 , Memória Epigenética , Síndrome de COVID-19 Pós-Aguda , Animais , Humanos , Camundongos , Diferenciação Celular , COVID-19/imunologia , Modelos Animais de Doenças , Células-Tronco Hematopoéticas , Inflamação/genética , Imunidade Treinada , Monócitos/imunologia , Síndrome de COVID-19 Pós-Aguda/genética , Síndrome de COVID-19 Pós-Aguda/imunologia , Síndrome de COVID-19 Pós-Aguda/patologia
2.
Cell ; 148(1-2): 259-72, 2012 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-22225612

RESUMO

Identification of the factors critical to the tumor-initiating cell (TIC) state may open new avenues in cancer therapy. Here we show that the metabolic enzyme glycine decarboxylase (GLDC) is critical for TICs in non-small cell lung cancer (NSCLC). TICs from primary NSCLC tumors express high levels of the oncogenic stem cell factor LIN28B and GLDC, which are both required for TIC growth and tumorigenesis. Overexpression of GLDC and other glycine/serine enzymes, but not catalytically inactive GLDC, promotes cellular transformation and tumorigenesis. We found that GLDC induces dramatic changes in glycolysis and glycine/serine metabolism, leading to changes in pyrimidine metabolism to regulate cancer cell proliferation. In the clinic, aberrant activation of GLDC correlates with poorer survival in lung cancer patients, and aberrant GLDC expression is observed in multiple cancer types. This link between glycine metabolism and tumorigenesis may provide novel targets for advancing anticancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/enzimologia , Transformação Celular Neoplásica , Glicina Desidrogenase (Descarboxilante)/metabolismo , Neoplasias Pulmonares/metabolismo , Sequência de Aminoácidos , Antígenos CD/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Moléculas de Adesão Celular Neuronais/metabolismo , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/metabolismo , Proteínas Fetais/metabolismo , Glicina/metabolismo , Humanos , Dados de Sequência Molecular , Neoplasias/enzimologia , Neoplasias/genética , Proteínas de Ligação a RNA , Alinhamento de Sequência , Serina/metabolismo , Thermus thermophilus/enzimologia , Transplante Heterólogo
3.
Chem Rev ; 123(15): 9397-9446, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37417731

RESUMO

The proportion of approved chiral drugs and drug candidates under medical studies has surged dramatically over the past two decades. As a consequence, the efficient synthesis of enantiopure pharmaceuticals or their synthetic intermediates poses a profound challenge to medicinal and process chemists. The significant advancement in asymmetric catalysis has provided an effective and reliable solution to this challenge. The successful application of transition metal catalysis, organocatalysis, and biocatalysis to the medicinal and pharmaceutical industries has promoted drug discovery by efficient and precise preparation of enantio-enriched therapeutic agents, and facilitated the industrial production of active pharmaceutical ingredient in an economic and environmentally friendly fashion. The present review summarizes the most recent applications (2008-2022) of asymmetric catalysis in the pharmaceutical industry ranging from process scales to pilot and industrial levels. It also showcases the latest achievements and trends in the asymmetric synthesis of therapeutic agents with state of the art technologies of asymmetric catalysis.


Assuntos
Indústria Farmacêutica , Estereoisomerismo , Biocatálise , Catálise
4.
Nano Lett ; 24(29): 8887-8893, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38984749

RESUMO

The synthesis of transition metal nitrides nanocrystals (TMNs NCs) has posed a significant challenge due to the limited reactivity of nitrogen sources at lower temperatures and the scarcity of available synthesis methods. In this study, we present a novel colloidal synthesis strategy for the fabrication of Cu3N nanorods (NRs). It is found that the trace oxygen (O2) plays an important role in the synthesis process. And a new mechanism for the formation of Cu3N is proposed. Subsequently, by employing secondary lateral epitaxial growth, the Cu3N-Cu2O heteronanostructures (HNs) can be prepared. The Cu3N NRs and Cu3N-Cu2O HNs were evaluated as precursor electrocatalysts for the CO2 reduction reaction (CO2RR). The Cu3N-Cu2O HNs demonstrate remarkable selectivity and stability with ethylene (C2H4) Faradaic efficiency (FE) up to 55.3%, surpassing that of Cu3N NRs. This study provides innovative insights into the reaction mechanism of colloidal synthesis of TMNs NCs and presents alternative options for designing cost-effective electrocatalysts to achieve carbon neutrality.

5.
Crit Rev Clin Lab Sci ; : 1-15, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041650

RESUMO

Immunoglobulin G (IgG) and immunoglobulin M (IgM) testing are commonly used to determine infection status. Typically, the detection of IgM indicates an acute or recent infection, while the presence of IgG alone suggests a chronic or past infection. However, relying solely on IgG and IgM antibody positivity may not be sufficient to differentiate acute from chronic infections. This limitation arises from several factors. The prolonged presence of IgM can complicate diagnostic interpretations, and false positive IgM results often arise from antibody cross-reactivity with various antigens. Additionally, IgM may remain undetectable in prematurely collected samples or in individuals who are immunocompromised, further complicating accurate diagnosis. As a result, additional diagnostic tools are required to confirm infection status. Avidity is a measure of the strength of the binding between an antigen and antibody. Avidity-based assays have been developed for various infectious agents, including toxoplasma, cytomegalovirus (CMV), SARS-CoV-2, and avian influenza, and are promising tools in clinical diagnostics. By measuring the strength of antibody binding, they offer critical insights into the maturity of the immune response. These assays are instrumental in distinguishing between acute and chronic or past infections, monitoring disease progression, and guiding treatment decisions. The development of automated platforms has optimized the testing process by enhancing efficiency and minimizing the risk of manual errors. Additionally, the recent advent of real-time biosensor immunoassays, including the label-free immunoassays (LFIA), has further amplified the capabilities of these assays. These advances have expanded the clinical applications of avidity-based assays, making them useful tools for the diagnosis and management of various infectious diseases. This review is structured around several key aspects of IgG avidity in clinical diagnosis, including: (i) a detailed exposition of the IgG affinity maturation process; (ii) a thorough discussion of the IgG avidity assays, including the recently emerged biosensor-based approaches; and (iii) an examination of the applications of IgG avidity in clinical diagnosis. This review is intended to contribute toward the development of enhanced diagnostic tools through critical assessment of the present landscape of avidity-based testing, which allows us to identify the existing knowledge gaps and highlight areas for future investigation.

6.
Br J Cancer ; 130(11): 1819-1827, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38594370

RESUMO

BACKGROUND: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. METHODS: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. RESULTS: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR, with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance. CONCLUSION: The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Amplificação de Genes , Metotrexato , Tetra-Hidrofolato Desidrogenase , Humanos , Metotrexato/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Tetra-Hidrofolato Desidrogenase/genética , Tetra-Hidrofolato Desidrogenase/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Antimetabólitos Antineoplásicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genômica/métodos
7.
Small ; 20(25): e2307995, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38212277

RESUMO

A simple, reliable method for identifying ß-lactoglobulin (ß-LG) in dairy products is needed to protect those with ß-LG allergies. A common, practical strategy for target detection is designing simplified nucleic acid nanodevices by integrating functional components. This work presents a label-free modular ß-LG aptasensor consisting of an aptamer-loop G-quadruplex (G4), the working conformation of which is regulated by conformational antagonism to ensure respective module functionality and the related signal transduction. The polymorphic conformations of the module-fused sequence are systematically characterized, and the cause is revealed as shifting antagonistic equilibrium. Combined with conformational folding dynamics, this helped regulate functional conformations by fine-tuning the sequences. Furthermore, the principle of specific ß-LG detection by parallel G4 topology is examined as binding on the G4 aptamer loop by ß-LG to reinforce the G4 topology and fluorescence. Finally, a label-free, assembly-free, succinct, and turn-on fluorescent aptasensor is established, achieving excellent sensitivity across five orders of magnitude, rapidly detecting ß-LG within 22-min. This study provides a generalizable approach for the conformational regulation of module-fused G4 sequences and a reference model for creating simplified sensing devices for a variety of targets.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Quadruplex G , Lactoglobulinas , Lactoglobulinas/química , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos
8.
Opt Express ; 32(12): 21855-21865, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859529

RESUMO

A gas detection method based on CH3NH3PbI3 (MAPbI3) and poly (3,4-ethylenedioxythiophene): poly (4-styrene sulfonate) (PEDOT:PSS) composite photodetectors (PDs) is proposed. The operation of the PD primarily relies on the photoelectric effect within the visible light band. Our study involves constructing a gas detection system based on tunable diode laser spectroscopy (TDLAS) and MAPbI3/PEDOT:PSS PD, and O2 was selected as the target analyte. The system has achieved a minimum detection limit (MDL) of 0.12% and a normalized noise equivalent absorption coefficient (NNEA) of 8.83 × 10-11 cm-1⋅W⋅Hz-1/2. Furthermore, the Allan deviation analysis results indicate that the system can obtain sensitivity levels as low as 0.058% over an averaging time of 328 seconds. This marks the first use of MAPbI3/PEDOT:PSS PD in gas detection based on TDLAS. Despite the detector's performance leaves much to be desired, this innovation offers a new approach to developing spectral based gas detection system.

9.
Langmuir ; 40(3): 1941-1949, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38207337

RESUMO

The tribological behavior of carboxylic acids, especially oleic acid, in boundary lubrication conditions is a subject of interest. This study presents the results of four-ball tribological tests conducted under varying contact pressures and sliding speeds. The findings reveal a critical turning speed within a confined zone, which causes a significant change in the frictional performances of oleic acid, leading to the formation of an ultralow wear tribofilm. This tribofilm, predominantly composed of oxyhydrogen compounds and hydrocarbons with more than five carbon atoms, is generated by the molecular action of oleic acid. Reactive nonequilibrium molecular dynamics simulations demonstrate that the shear speed-dependent decomposition modes of oleic acid and the transformation of the lubrication slip interface are the fundamental processes underlying the formation of this ultralow-wear boundary tribofilm.

10.
Pharmacol Res ; 201: 107105, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367917

RESUMO

Chronic interstitial fibrosis presents a significant challenge to the long-term survival of transplanted kidneys. Our research has shown that reduced expression of acyl-coenzyme A oxidase 1 (ACOX1), which is the rate-limiting enzyme in the peroxisomal fatty acid ß-oxidation pathway, contributes to the development of fibrosis in renal allografts. ACOX1 deficiency leads to lipid accumulation and excessive oxidation of polyunsaturated fatty acids (PUFAs), which mediate epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) reorganization respectively, thus causing fibrosis in renal allografts. Furthermore, activation of Toll-like receptor 4 (TLR4)-nuclear factor kappa-B (NF-κB) signaling induced ACOX1 downregulation in a DNA methyltransferase 1 (DNMT1)-dependent manner. Overconsumption of PUFA resulted in endoplasmic reticulum (ER) stress, which played a vital role in facilitating ECM reorganization. Supplementation with PUFAs contributed to delayed fibrosis in a rat model of renal transplantation. The study provides a novel therapeutic approach that can delay chronic interstitial fibrosis in renal allografts by targeting the disorder of lipid metabolism.


Assuntos
Acil-CoA Oxidase , Transplante de Rim , Rim , Doenças Metabólicas , Animais , Ratos , Acil-CoA Oxidase/metabolismo , Aloenxertos , Fibrose , Rim/patologia , Lipídeos
11.
BMC Infect Dis ; 24(1): 1149, 2024 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-39396949

RESUMO

BACKGROUND: The best antiviral treatment for chronic hepatitis B (CHB) poses a complex challenge. The treatment effect of the combination of nucleoside analogues (NAs) and pegylated interferon alpha (PegIFN) was still in debate. METHODS: We studied patients treated with NAs and PegIFN-2b at our institution from November 2019 to January 2022. Logistic regression identified independent factors influencing clinical cure. The predictive accuracy of the formula was assessed using the Receiver operating characteristic (ROC) curve at different time points (before therapy, 12 weeks, and 24 weeks into treatment). RESULTS: A total of 120 patients were enrolled in the final analysis. Among the cohort of patients under study, 71 (59.1%) patients had clinical cure while 49 (40.9%) patients did not. Hepatitis B surface antigen (HBsAg) at baseline and age were the powerful variables predicting the clearance of HBsAg. The area under the ROC (AUC) was 0.907 for pre-treatment predictive model, 0.958 for 12-week predictive model and 0.747 for 24-week predictive model. CONCLUSION: This study provided predictive formulas for clinical cure, offering valuable insights for CHB treatment. PegIFN and NAs exhibited efficacy. Future research that explores additional factors, such as HBV genotype, in a larger cohort study is needed.


Assuntos
Antivirais , Hepatite B Crônica , Interferon-alfa , Polietilenoglicóis , Proteínas Recombinantes , Humanos , Hepatite B Crônica/tratamento farmacológico , Masculino , Interferon-alfa/uso terapêutico , Antivirais/uso terapêutico , Feminino , Adulto , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Nucleosídeos/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Quimioterapia Combinada , Curva ROC , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Estudos Retrospectivos , Interferon alfa-2
12.
Clin Chem Lab Med ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39238286

RESUMO

This opinion article highlights the critical role of laboratory medicine and emerging technologies in cardiovascular risk reduction through exposome analysis. The exposome encompasses all external and internal exposures an individual faces throughout their life, influencing the onset and progression of cardiovascular diseases (CVD). Integrating exposome data with genetic information allows for a comprehensive understanding of the multifactorial causes of CVD, facilitating targeted preventive interventions. Laboratory medicine, enhanced by advanced technologies such as metabolomics and artificial intelligence (AI), plays a pivotal role in identifying and mitigating these exposures. Metabolomics provides detailed insights into metabolic changes triggered by environmental factors, while AI efficiently processes complex datasets to uncover patterns and associations. This integration fosters a proactive approach in public health and personalized medicine, enabling earlier detection and intervention. The article calls for global implementation of exposome technologies to improve population health, emphasizing the need for robust technological platforms and policy-driven initiatives to seamlessly integrate environmental data with clinical diagnostics. By harnessing these innovative technologies, laboratory medicine can significantly contribute to reducing the global burden of cardiovascular diseases through precise and personalized risk mitigation strategies.

13.
Appl Opt ; 63(2): 327-337, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38227225

RESUMO

Source mask optimization (SMO) is a widely used computational lithography technique for compensating lithographic distortion. However, line-end shortening is still a key factor that cannot be easily corrected and affects the image fidelity of lithography at advanced nodes. This paper proposes a source mask optimization method that suppresses line-end shortening and improves lithography fidelity. An adaptive hybrid weight method is employed to increase the weights of the line end during the optimization, which adaptively updates the weights in each iteration according to the edge placement error (EPE). A cost function containing a penalty term based on the normalized image log slope (NILS) is established to ensure the fidelity of the overall feature when paying more attention to the line-end region. The scope of this penalty term is regulated by widening and extending the split contour to further reduce the line-end shortening. Simulation results show that the proposed method can effectively suppress the line-end shortening and improve the lithography fidelity compared with the traditional SMO method.

14.
Molecules ; 29(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38893506

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a significant hepatic condition that has gained worldwide attention. Kaempferol (Kae), renowned for its diverse biological activities, including anti-inflammatory, antioxidant, anti-aging, and cardio-protective properties, has emerged as a potential therapeutic candidate for non-alcoholic steatohepatitis (NASH). Despite its promising therapeutic potential, the precise underlying mechanism of Kae's beneficial effects in NASH remains unclear. Therefore, this study aims to clarify the mechanism by conducting comprehensive in vivo and in vitro experiments. RESULTS: In this study, a murine model of non-alcoholic steatohepatitis (NASH) was established by feeding C57BL/6 female mice a high-fat diet for 12 weeks. Kaempferol (Kae) was investigated for its ability to modulate systemic inflammatory responses and lipid metabolism in this model (20 mg/kg per day). Notably, Kae significantly reduced the expression of NLRP3-ASC/TMS1-Caspase 3, a crucial mediator of liver tissue inflammation. Additionally, in a HepG2 cell model induced with palmitic acid/oleic acid (PA/OA) to mimic NASH conditions, Kae demonstrated the capacity to decrease lipid droplet accumulation and downregulate the expression of NLRP3-ASC/TMS1-Caspase 3 (20 µM and the final concentration to 20 nM). These findings suggest that Kae may hold therapeutic potential in the treatment of NASH by targeting inflammatory and metabolic pathways. CONCLUSIONS: These findings suggest that kaempferol holds potential as a promising therapeutic intervention for ameliorating non-alcoholic fatty liver disease (NAFLD).


Assuntos
Caspase 3 , Quempferóis , Proteína 3 que Contém Domínio de Pirina da Família NLR , Neutrófilos , Hepatopatia Gordurosa não Alcoólica , Transdução de Sinais , Quempferóis/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Camundongos , Humanos , Transdução de Sinais/efeitos dos fármacos , Caspase 3/metabolismo , Feminino , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Células Hep G2 , Dieta Hiperlipídica/efeitos adversos
15.
Angew Chem Int Ed Engl ; 63(2): e202315782, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38018480

RESUMO

Dendritic cell vaccine (DCV) holds great potential in tumor immunotherapy owing to its potent ability in eliciting tumor-specific immune responses. Aiming at engineering enhanced DCV, we report the first effort to construct a glycopolymer-engineered DC vaccine (G-DCV) via metabolicglycoengineering and copper-free click-chemistry. Model G-DCV was prepared by firstly delivering tumor antigens, ovalbumin (OVA) into dendritic cells (DC) with fluoroalkane-grafted polyethyleneimines, followed by conjugating glycopolymers with a terminal group of dibenzocyclooctyne (DBCO) onto dendritic cells. Compared to unmodified DCV, our G-DCV could induce stronger T cell activation due to the enhanced adhesion between DCs and T cells. Notably, such G-DCV could more effectively inhibit the growth of the mouse B16-OVA (expressing OVA antigen) tumor model after adoptive transfer. Moreover, by combination with an immune checkpoint inhibitor, G-DCV showed further increased anti-tumor effects in treating different tumor models. Thus, our work provides a novel strategy to enhance the therapeutic effectiveness of DC vaccines.


Assuntos
Neoplasias , Vacinas , Camundongos , Animais , Linfócitos T , Antígenos de Neoplasias , Neoplasias/metabolismo , Ovalbumina , Membrana Celular , Células Dendríticas/metabolismo
16.
Angew Chem Int Ed Engl ; 63(24): e202402853, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598262

RESUMO

In the development of dendritic cell (DC) vaccines, the maturation of DCs is a critical stage. Adjuvants play a pivotal role in the maturation of DCs, with a major concern being to ensure both efficacy and safety. This study introduces an innovative approach that combines high efficacy with safety through the synthesis of micro-adjuvants grafted with copolymers of 2-(methacrylamido) glucopyranose (MAG) and methacryloxyethyl trimethyl ammonium chloride (DMC). The utilization of metal-free surface-initiated atom transfer radical polymerization enables the production of safe and recyclable adjuvants. These micrometer-sized adjuvants surpass the optimal size range for cellular endocytosis, enabling the retrieval and reuse of them during the ex vivo maturation process, mitigating potential toxicity concerns associated with the endocytosis of non-metabolized nanoparticles. Additionally, the adjuvants exhibit a "micro-ligand-mediated maturation enhancement" effect for DC maturation. This effect is influenced by the shape of the particle, as evidenced by the distinct promotion effects of rod-like and spherical micro-adjuvants with comparable sizes. Furthermore, the porous structure of the adjuvants enables them to function as cargo-carrying "micro-shuttles", releasing antigens upon binding to DCs to facilitate efficient antigen delivery.


Assuntos
Adjuvantes Imunológicos , Células Dendríticas , Polimerização , Células Dendríticas/metabolismo , Células Dendríticas/imunologia , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/síntese química , Vacinas/química , Vacinas/imunologia , Tamanho da Partícula , Camundongos , Animais , Polímeros/química , Polímeros/farmacologia , Polímeros/síntese química
17.
Angew Chem Int Ed Engl ; : e202414720, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39166363

RESUMO

Phase control over cation exchange (CE) reactions has emerged as an important approach for the synthesis of nanomaterials (NMs), enabling precise determination of their reactivity and properties. Although factors such as crystal structure and morphology have been studied for the phase engineering of CE reactions in NMs, there remains a lack of systematic investigation to reveal the impact for the factors in heterogeneous materials. Herein, we report a molybdenum disulfide induced phase control method for synthesizing multidimensional Co3S4-MoS2 heteronanostructures (HNs) via cation exchange. MoS2 in parent Cu1.94S-MoS2 HNs are proved to affect the thermodynamics and kinetics of CE reactions, and facilitate the formation of Co3S4-MoS2 HNs with controlled phase. This MoS2 induced phase control method can be extended to other parent HNs with multiple dimensions, which shows its diversity. Further, theoretical calculations demonstrate that Co3S4 (111)/MoS2 (001) exhibits a higher adhesion work, providing further evidence that MoS2 enables phase control in the HNs CE reactions, inducing the generation of novel Co3S4-MoS2 HNs. As a proof-of-concept application for crystal phase- and dimensionality-dependent of cobalt sulfide based HNs, the obtained Co3S4-MoS2 heteronanoplates (HNPls) show remarkable performance in hydrogen evolution reactions (HER) under alkaline media. This synthetic methodology provides a unique design strategy to control the crystal structure and fills the gap in the study of heterogeneous materials on CE reaction over phase engineering that are otherwise inaccessible.

18.
Clin Chem ; 69(11): 1238-1246, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37664912

RESUMO

BACKGROUND: Artificial intelligence (AI) conversational agents, or chatbots, are computer programs designed to simulate human conversations using natural language processing. They offer diverse functions and applications across an expanding range of healthcare domains. However, their roles in laboratory medicine remain unclear, as their accuracy, repeatability, and ability to interpret complex laboratory data have yet to be rigorously evaluated. CONTENT: This review provides an overview of the history of chatbots, two major chatbot development approaches, and their respective advantages and limitations. We discuss the capabilities and potential applications of chatbots in healthcare, focusing on the laboratory medicine field. Recent evaluations of chatbot performance are presented, with a special emphasis on large language models such as the Chat Generative Pre-trained Transformer in response to laboratory medicine questions across different categories, such as medical knowledge, laboratory operations, regulations, and interpretation of laboratory results as related to clinical context. We analyze the causes of chatbots' limitations and suggest research directions for developing more accurate, reliable, and manageable chatbots for applications in laboratory medicine. SUMMARY: Chatbots, which are rapidly evolving AI applications, hold tremendous potential to improve medical education, provide timely responses to clinical inquiries concerning laboratory tests, assist in interpreting laboratory results, and facilitate communication among patients, physicians, and laboratorians. Nevertheless, users should be vigilant of existing chatbots' limitations, such as misinformation, inconsistencies, and lack of human-like reasoning abilities. To be effectively used in laboratory medicine, chatbots must undergo extensive training on rigorously validated medical knowledge and be thoroughly evaluated against standard clinical practice.


Assuntos
Serviços de Laboratório Clínico , Medicina , Humanos , Laboratórios Clínicos , Inteligência Artificial , Laboratórios
19.
Clin Chem ; 69(11): 1260-1269, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37738611

RESUMO

BACKGROUND: Measuring parathyroid hormone-related peptide (PTHrP) helps diagnose the humoral hypercalcemia of malignancy, but is often ordered for patients with low pretest probability, resulting in poor test utilization. Manual review of results to identify inappropriate PTHrP orders is a cumbersome process. METHODS: Using a dataset of 1330 patients from a single institute, we developed a machine learning (ML) model to predict abnormal PTHrP results. We then evaluated the performance of the model on two external datasets. Different strategies (model transporting, retraining, rebuilding, and fine-tuning) were investigated to improve model generalizability. Maximum mean discrepancy (MMD) was adopted to quantify the shift of data distributions across different datasets. RESULTS: The model achieved an area under the receiver operating characteristic curve (AUROC) of 0.936, and a specificity of 0.842 at 0.900 sensitivity in the development cohort. Directly transporting this model to two external datasets resulted in a deterioration of AUROC to 0.838 and 0.737, with the latter having a larger MMD corresponding to a greater data shift compared to the original dataset. Model rebuilding using site-specific data improved AUROC to 0.891 and 0.837 on the two sites, respectively. When external data is insufficient for retraining, a fine-tuning strategy also improved model utility. CONCLUSIONS: ML offers promise to improve PTHrP test utilization while relieving the burden of manual review. Transporting a ready-made model to external datasets may lead to performance deterioration due to data distribution shift. Model retraining or rebuilding could improve generalizability when there are enough data, and model fine-tuning may be favorable when site-specific data is limited.


Assuntos
Hipercalcemia , Neoplasias , Humanos , Proteína Relacionada ao Hormônio Paratireóideo , Curva ROC , Aprendizado de Máquina
20.
Opt Express ; 31(12): 19215-19235, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37381342

RESUMO

Inverse lithography technology (ILT), such as source mask optimization (SMO), is used to improve lithography performance. Usually, a single objective cost function is selected in ILT, and an optimal structure for one field point is achieved. The optimal structure is not the case for other images at full field points where the aberrations of the lithography system are different, even in high-quality lithography tools. The optimal structure that must match the high-performance images at the full field is urgently required for extreme ultraviolet lithography (EUVL). In contrast, multi-objective optimization algorithms (MOAs) limit the application of multi-objective ILT. Assigning target priority is incomplete in current MOAs, which results in the over-optimization of some targets and under-optimization of others. In this study, multi-objective ILT and a hybrid dynamic priority (HDP) algorithm were investigated and developed. High-performance images with high fidelity and high uniformity were obtained at multi-field and multi-clip areas across the die. A hybrid criterion was developed for the completion and reasonable prioritization of each target to ensure sufficient improvement. Compared to the current MOAs, the uniformity of images at full-field points was improved by up to 31.1% by the HDP algorithm in the case of multi-field wavefront error-aware SMO. The multi-clip source optimization (SO) problem showed the universality of the HDP algorithm to deal with different ILT problems. It acquired higher imaging uniformity than existing MOAs, which indicated that the HDP is more qualified for multi-objective ILT optimization than existing MOAs.

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