Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 208
Filtrar
1.
Polymers (Basel) ; 16(11)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38891404

RESUMO

The aim of this study is the fabrication of unprecedented neuroelectrodes, replete with exceptional biological and electrical attributes. Commencing with the synthesis of polyethylene glycol and polyethyleneimine-modified iron oxide nanoparticles, the grafting of Dimyristoyl phosphatidylcholine was embarked upon to generate DMPC-SPION nanoparticles. Subsequently, the deposition of DMPC-SPIONs onto a nickel-chromium alloy electrode facilitated the inception of an innovative neuroelectrode-DMPC-SPION. A meticulous characterization of DMPC-SPIONs ensued, encompassing zeta potential, infrared spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction analyses. Evaluations pertaining to hemolysis and cytotoxicity were conducted to ascertain the biocompatibility and biosafety of DMPC-SPIONs. Ultimately, a comprehensive assessment of the biocompatibility, electrochemical properties, and electrophysiological signal acquisition capabilities of DMPC-SPION neuroelectrodes was undertaken. These findings conclusively affirm the exemplary biocompatibility, electrochemical capabilities, and outstanding capability in recording electrical signals of DMPC-SPION neuroelectrodes, with an astounding 91.4% augmentation in electrode charge and a noteworthy 13% decline in impedance, with peak potentials reaching as high as 171 µV and an impressive signal-to-noise ratio of 15.92. Intriguingly, the novel DMPC-SPION neuroelectrodes herald an innovative pathway towards injury repair as well as the diagnosis and treatment of neurological disorders.

2.
Leukemia ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909089

RESUMO

Aberrations in the Hedgehog (Hh) signaling pathway are significantly prevailed in various cancers, including B-cell lymphoma. A critical facet of Hh signal transduction involves the dynamic regulation of the suppressor of fused homolog (SUFU)-glioma-associated oncogene homolog (GLI) complex within the kinesin family member 7 (KIF7)-supported ciliary tip compartment. However, the specific post-translational modifications of SUFU-GLI complex within this context have remained largely unexplored. Our study reveals a novel regulatory mechanism involving prolyl 4-hydroxylase 2 (P4HA2), which forms a complex with KIF7 and is essential for signal transduction of Hh pathway. We demonstrate that, upon Hh pathway activation, P4HA2 relocates alongside KIF7 to the ciliary tip. Here, it hydroxylates SUFU to inhibit its function, thus amplifying the Hh signaling. Moreover, the absence of P4HA2 significantly impedes B lymphoma progression. This effect can be attributed to the suppression of Hh signaling in stromal fibroblasts, resulting in decreased growth factors essential for malignant proliferation of B lymphoma cells. Our findings highlight the role of P4HA2-mediated hydroxylation in modulating Hh signaling and propose a novel stromal-targeted therapeutic strategy for B-cell lymphoma.

3.
Zhongguo Gu Shang ; 37(5): 519-26, 2024 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-38778538

RESUMO

OBJECTIVE: To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis, by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis. METHODS: Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected, and the samples of necrotic osteonecrosis from chronic osteomyelitis (necrotic group), and normal bone tissue (control group) were collected. Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform, and the gene expression in bone tissue was calculated by FPKM. The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group. Genes were enriched by GO and KEGG. MAP3K7 and NFATC1 were selected as differential targets in the verification experiments, by using rat osteomyelitis animal model and immunohistochemical analysis. RESULTS: A total of 5548 differentially expressed genes were obtained by high throughput sequencing by comparing the necrotic group and control group, including 2701 up-regulated and 2847 down-regulated genes. The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened, the common genes expressed in both MAPK and osteoclast differentiation pathway were (inhibitor of nuclear factor κ subunit Beta, IκBKß), (mitogen-activated protein kinase 7, MAP3K7), (nuclear factor of activated t cells 1, NFATC1) and (nuclear factor Kappa B subunit 2, NFκB2). In rat osteomyelitis model, MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue. CONCLUSION: Based on the transcriptome analysis, the MAPK signaling and osteoclast differentiation pathways were closely related to chronic osteomyelitis, and the key genes IκBKß, MAP3K7, NFATC1, NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.


Assuntos
Osteomielite , Transcriptoma , Osteomielite/genética , Animais , Humanos , Doença Crônica , Masculino , Ratos , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Perfilação da Expressão Gênica , Osso e Ossos/metabolismo , Ratos Sprague-Dawley , Feminino , Sistema de Sinalização das MAP Quinases/genética
4.
Nanomaterials (Basel) ; 14(10)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38786784

RESUMO

Iron oxide nanoparticles (IONs) with good water dispersibility were prepared by the thermal decomposition of iron acetylacetonate (Fe(acac)3) in the high-boiling organic solvent polyethylene glycol (PEG) using polyethyleneimine (PEI) as a modifier. The nucleation and growth processes of the crystals were separated during the reaction process by batch additions of the reaction material, which could inhibit the nucleation but maintain the crystal growth, and products with larger particle sizes and high saturation magnetization were obtained. The method of batch addition of the reactant prepared IONs with the largest particle size and the highest saturation magnetization compared with IONs reported using PEG as the reaction solvent. The IONs prepared by this method also retained good water dispersibility. Therefore, these IONs are potentially suitable for the magnetic separation of cells, proteins, or nucleic acids when large magnetic responses are needed.

5.
World J Gastrointest Oncol ; 16(5): 1725-1736, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38764838

RESUMO

Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques. These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research. This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids, and patient-derived organoids. The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed. The construction of gastric organoids involves several key steps, including cell extraction and culture, three-dimensional structure formation, and functional expression. Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori. In addition, in drug screening and development, gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials. They can also be used for precision medicine according to the specific conditions of patients with gastric cancer, to assess drug resistance, and to predict the possibility of adverse reactions. However, despite the impressive progress in the field of gastric organoids, there are still many unknowns that need to be addressed, especially in the field of regenerative medicine. Meanwhile, the reproducibility and consistency of organoid cultures are major challenges that must be overcome. These challenges have had a significant impact on the development of gastric organoids. Nonetheless, as technology continues to advance, we can foresee more comprehensive research in the construction of gastric organoids. Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.

6.
Free Radic Biol Med ; 220: 56-66, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38697489

RESUMO

Apart from dopaminergic neurotoxicity, exposure to rotenone, a commonly used insecticide in agriculture, also adversely affects hippocampal and cortical neurons, resulting in cognitive impairments in mice. We recently established a role of microglia-mediated neuroinflammation in rotenone-elicited deficits of cognition, yet the mechanisms remain elusive. Here, we investigated the involvement of NADPH oxidase 2 (NOX2) catalytic subunit gp91phox in rotenone-induced cognitive deficits and the associated mechanisms. Our study demonstrated that rotenone exposure elevated expression of gp91phox and phosphorylation of the NOX2 cytosolic subunit p47phox, along with NADPH depletion in the hippocampus and cortex of mice, indicating NOX2 activation. Specific knockdown of gp91phox in microglia via adeno-associated virus delivery resulted in reduced microglial activation, proinflammatory gene expression and improved learning and memory capacity in rotenone-intoxicated mice. Genetic deletion of gp91phox also reversed rotenone-elicited cognitive dysfunction in mice. Furthermore, microglial gp91phox knockdown attenuated neuronal damage and synaptic loss in mice. This intervention also suppressed iron accumulation, disruption of iron-metabolism proteins and iron-dependent lipid peroxidation and restored the balance of ferroptosis-related parameters, including GPX4, SLC711, PTGS2, and ACSL4 in rotenone-lesioned mice. Intriguingly, pharmacological inhibition of ferroptosis with liproxstatin-1 conferred protection against rotenone-induced neurodegeneration and cognitive dysfunction in mice. In summary, our findings underscored the contribution of microglial gp91phox-dependent neuroinflammation and ferroptosis to learning and memory dysfunction in rotenone-lesioned mice. These results provided valuable insights into the pathogenesis of cognitive deficits associated with pesticide-induced Parkinsonism, suggesting potential therapeutic avenues for intervention.


Assuntos
Ferroptose , Transtornos da Memória , Microglia , NADPH Oxidase 2 , Doenças Neuroinflamatórias , Rotenona , Animais , Camundongos , NADPH Oxidase 2/metabolismo , NADPH Oxidase 2/genética , Microglia/metabolismo , Microglia/patologia , Microglia/efeitos dos fármacos , Rotenona/toxicidade , Ferroptose/efeitos dos fármacos , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/induzido quimicamente , Doenças Neuroinflamatórias/genética , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Transtornos da Memória/genética , Transtornos da Memória/patologia , Masculino , Camundongos Endogâmicos C57BL , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Neurônios/metabolismo , Neurônios/patologia , Neurônios/efeitos dos fármacos , Camundongos Knockout
7.
Anal Methods ; 16(22): 3577-3586, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38787692

RESUMO

Analysis of exosomes provides important information for rapid and non-invasive screening of tumors. However, sensitive and convenient detection of exosomes remains technically challenging to date. Herein, a colorimetric aptasensor based on the light-stimulated oxidase-mimicking activity of FITC was constructed for detecting ovarian cancer (OC) exosomes. The aptasensor contained an EpCAM aptamer to capture OC exosomes. Cholesterol and fluorescein (FITC) were used to modify either end of the DNA (DNA anchor). The DNA anchor could combine with exosomes through a hydrophobic reaction between cholesterol and the lipid membrane. FITC oxidized 3,3',5,5'-tetramethylbenzidine (TMB) under a 365 nm LED light source in a temporally controllable manner under mild conditions, causing the solution to change from colorless to blue, and the corresponding UV-vis absorbance increased. Based on this principle, the exosomes were qualitatively analyzed by observing the color change with the naked eye. In parallel, the exosome concentration was also detected using UV-vis spectrophotometry. The linear range was from 2 × 105 to 100 × 105 particles per mL with a limit of detection of 1.77 × 105 particles per mL. The developed aptasensor also exhibited favorable selectivity and could discriminate the exosomes from OC cells and normal cells. Besides, the receiver operating characteristic (ROC) curve demonstrates that it is possible to distinguish between patients with OC and healthy donors (HDs) using exosomes as the biomarker. Our technology may expand the applications of DNA-based detection method-enabled OC diagnostic tools.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Colorimetria , Exossomos , Exossomos/química , Exossomos/metabolismo , Humanos , Colorimetria/métodos , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Feminino , Neoplasias Ovarianas , Oxirredutases/química , Oxirredutases/metabolismo , Luz , Limite de Detecção , Fluoresceína/química , Benzidinas/química , Linhagem Celular Tumoral
8.
Eur J Clin Nutr ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38605191

RESUMO

BACKGROUND: In observational and prospective cohort studies, intake of sugar-sweetened beverages (SSBs) and pure fruit juice (PFJ) has been associated with cardiovascular disease (CVD). Still, the causality of the connection has not yet been determined. Our objective was to uncover the relationship between SSBs/PFJ and CVD. METHODS: Genetically predicted causal associations between SSBs/PFJ (obtained in a published genome-wide association study) and six common CVDs (atrial fibrillation (AF), angina, heart failure (HF), acute myocardial infarction, hypertension, and coronary atherosclerosis) were assessed using MR analytic modeling. The primary analysis method utilized was the inverse variance weighted (IVW) method, complemented by additional methods such as the weighted median method, MR Egger regression, Cochran's Q test, MR pleiotropy residual, funnel plot, Bonferroni correction, and others for MR analysis. To ensure the robustness of the findings, F-values were calculated as a complementary test to set looser thresholds for exposing genetic instrumental variables (P < 1e-5). RESULTS: The results of MR analysis suggested genetically causal associations between SSBs and AF (odds ratio (OR): 1.023; 95% confidence interval (CI) 1.007-1.038; P = 0.0039) as well as between PFJ and angina (OR: 0.968; 95% CI, 0.943-0.993; P = 0.0138) there was genetic causality. However, MR analysis showed no causal association between SSBs/PFJ and other CVD risks. CONCLUSION: This study suggests that there may be a potential causal relationship between SSBs intake and AF and a causal negative association between PFJ intake and angina.

9.
J Med Chem ; 67(6): 4376-4418, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38488755

RESUMO

In 2022, 23 new small molecule chemical entities were approved as drugs by the United States FDA, European Union EMA, Japan PMDA, and China NMPA. This review describes the synthetic approach demonstrated on largest scale for each new drug based on patent or primary literature. The synthetic routes highlight practical methods to construct molecules, sometimes on the manufacturing scale, to access the new drugs. Ten additional drugs approved in 2021 and one approved in 2020 are included that were not covered in the previous year's review.


Assuntos
Aprovação de Drogas , Estados Unidos , Japão , United States Food and Drug Administration , China
10.
J Am Board Fam Med ; 37(1): 118-128, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38448239

RESUMO

INTRODUCTION: Given the high sedative prescription rate, the sedative-associated morbidity, and mortality nationally (especially among veterans), we aimed to test the hypothesis that veteran status in the presence of chronic pain would be associated with greater sedative use when compared with nonveteran status. METHODS: The study participants were recruited by Community Health Workers (CHWs) through the ongoing community engagement program (HealthStreet) at the University of Florida. CHWs collected information on sociodemographic factors, health status, and past 30-day drug use patterns. RESULTS: The study sample comprised 4,732 male participants, of which 21% were veterans, 58% were Blacks and 8.4% had used prescription sedatives in the past 30 days. Veterans (vs nonveterans) were twice as likely to have used prescription sedatives in the past 30 days in the presence of chronic pain. CONCLUSIONS: Veterans with chronic pain are a high-risk population for current prescription sedative use.


Assuntos
Dor Crônica , Transtornos Relacionados ao Uso de Substâncias , Veteranos , Adulto , Humanos , Masculino , Estados Unidos , Hipnóticos e Sedativos/efeitos adversos , Dor Crônica/tratamento farmacológico , Vida Independente , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
11.
BMC Public Health ; 24(1): 749, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38459461

RESUMO

BACKGROUND: Racial/ethnic disparities in the HIV care continuum have been well documented in the US, with especially striking inequalities in viral suppression rates between White and Black persons with HIV (PWH). The South is considered an epicenter of the HIV epidemic in the US, with the largest population of PWH living in Florida. It is unclear whether any disparities in viral suppression or immune reconstitution-a clinical outcome highly correlated with overall prognosis-have changed over time or are homogenous geographically. In this analysis, we 1) investigate longitudinal trends in viral suppression and immune reconstitution among PWH in Florida, 2) examine the impact of socio-ecological factors on the association between race/ethnicity and clinical outcomes, 3) explore spatial and temporal variations in disparities in clinical outcomes. METHODS: Data were obtained from the Florida Department of Health for 42,369 PWH enrolled in the Ryan White program during 2008-2020. We linked the data to county-level socio-ecological variables available from County Health Rankings. GEE models were fit to assess the effect of race/ethnicity on immune reconstitution and viral suppression longitudinally. Poisson Bayesian hierarchical models were fit to analyze geographic variations in racial/ethnic disparities while adjusting for socio-ecological factors. RESULTS: Proportions of PWH who experienced viral suppression and immune reconstitution rose by 60% and 45%, respectively, from 2008-2020. Odds of immune reconstitution and viral suppression were significantly higher among White [odds ratio =2.34, 95% credible interval=2.14-2.56; 1.95 (1.85-2.05)], and Hispanic [1.70 (1.54-1.87); 2.18(2.07-2.31)] PWH, compared with Black PWH. These findings remained unchanged after accounting for socio-ecological factors. Rural and urban counties in north-central Florida saw the largest racial/ethnic disparities. CONCLUSIONS: There is persistent, spatially heterogeneous, racial/ethnic disparity in HIV clinical outcomes in Florida. This disparity could not be explained by socio-ecological factors, suggesting that further research on modifiable factors that can improve HIV outcomes among Black and Hispanic PWH in Florida is needed.


Assuntos
Etnicidade , Infecções por HIV , Humanos , Teorema de Bayes , Florida/epidemiologia , Disparidades em Assistência à Saúde , Hispânico ou Latino , Infecções por HIV/epidemiologia , Brancos , Negro ou Afro-Americano
12.
AIDS Behav ; 28(7): 2286-2295, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38551720

RESUMO

Substance use disorder (SUD), a common comorbidity among people with HIV (PWH), adversely affects HIV clinical outcomes and HIV-related comorbidities. However, less is known about the incidence of different chronic conditions, changes in overall comorbidity burden, and health care utilization by SUD status and patterns among PWH in Florida, an area disproportionately affected by the HIV epidemic. We used electronic health records (EHR) from a large southeastern US consortium, the OneFlorida + clinical research data network. We identified a cohort of PWH with 3 + years of EHRs after the first visit with HIV diagnosis. International Classification of Diseases (ICD) codes were used to identify SUD and comorbidity conditions listed in the Charlson comorbidity index (CCI). A total of 42,271 PWH were included (mean age 44.5, 52% Black, 45% female). The prevalence SUD among PWH was 45.1%. Having a SUD diagnosis among PWH was associated with a higher incidence for most of the conditions listed on the CCI and faster increase in CCI score overtime (rate ratio = 1.45, 95%CI 1.42, 1.49). SUD in PWH was associated with a higher mean number of any care visits (21.7 vs. 14.8) and more frequent emergency department (ED, 3.5 vs. 2.0) and inpatient (8.5 vs. 24.5) visits compared to those without SUD. SUD among PWH was associated with a higher comorbidity burden and more frequent ED and inpatient visits than PWH without a diagnosis of SUD. The high SUD prevalence and comorbidity burden call for improved SUD screening, treatment, and integrated care among PWH.


Assuntos
Comorbidade , Infecções por HIV , Aceitação pelo Paciente de Cuidados de Saúde , Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Florida/epidemiologia , Masculino , Infecções por HIV/epidemiologia , Adulto , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Prevalência , Incidência , Registros Eletrônicos de Saúde , Efeitos Psicossociais da Doença
14.
Drug Alcohol Depend ; 258: 111272, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38555662

RESUMO

BACKGROUND: Polysubstance use is highly prevalent among persons who use cocaine; however, little is known about how alcohol and cannabis are used with cocaine. We identified temporal patterns of cocaine+alcohol and cocaine+cannabis polysubstance use to inform more translationally relevant preclinical models. METHODS: Participants who used cocaine plus alcohol and/or cannabis at least once in the past 30 days (n=148) were interviewed using the computerized Substance Abuse Module and the newer Polysubstance Use-Temporal Patterns Section. For each day in the past 30 days, participants reported whether they had used cocaine, alcohol, and cannabis; if any combinations of use were endorsed, participants described detailed hourly use of each substance on the most "typical day" for the combination. Sequence analysis and hierarchical clustering were applied to identify patterns of timing of drug intake on typical days of cocaine polysubstance use. RESULTS: We identified five temporal patterns among the 180 sequences of reported cocaine polysubstance use: 1) limited cocaine/cocaine+alcohol use (53%); 2) extensive cannabis then cocaine+alcohol+cannabis use (22%); 3) limited alcohol/cannabis then cocaine+alcohol use (13%); 4) extensive cocaine+cannabis then cocaine+alcohol+cannabis use (4%); and 5) extensive cocaine then cocaine+alcohol use (8%). While drug intake patterns differed, prevalence of use disorders did not. CONCLUSIONS: Patterns were characterized by cocaine, alcohol, and cannabis polysubstance use and by the timing, order, duration, and quantity of episode-level substance use. The identification of real-world patterns of cocaine polysubstance use represents an important step toward developing laboratory models that accurately reflect human behavior.


Assuntos
Consumo de Bebidas Alcoólicas , Transtornos Relacionados ao Uso de Cocaína , Humanos , Masculino , Feminino , Adulto , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Consumo de Bebidas Alcoólicas/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Abuso de Maconha/epidemiologia , Fatores de Tempo
15.
Insights Imaging ; 15(1): 23, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270724

RESUMO

BACKGROUND: To investigate whether intratumoral and peritumoral radiomics may predict pathological responses after neoadjuvant chemotherapy against advanced gastric cancer. METHODS: Clinical, pathological, and CT data from 231 patients with advanced gastric cancer who underwent neoadjuvant chemotherapy at our hospital between July 2014 and February 2022 were retrospectively collected. Patients were randomly divided into a training group (n = 161) and a validation group (n = 70). The support vector machine classifier was used to establish radiomics models. A clinical model was established based on the selected clinical indicators. Finally, the radiomics and clinical models were combined to generate a radiomics-clinical model. ROC analyses were used to evaluate the prediction efficiency for each model. Calibration curves and decision curves were used to evaluate the optimal model. RESULTS: A total of 91 cases were recorded with good response and 140 with poor response. The radiomics model demonstrated that the AUC was higher in the combined model than in the intratumoral and peritumoral models (training group: 0.949, 0.943, and 0.846, respectively; validation group: 0.815, 0.778, and 0.701, respectively). Age, Borrmann classification, and Lauren classification were used to construct the clinical model. Among the radiomics-clinical models, the combined-clinical model showed the highest AUC (training group: 0.960; validation group: 0.843), which significantly improved prediction efficiency. CONCLUSION: The peritumoral model provided additional value in the evaluation of pathological response after neoadjuvant chemotherapy against advanced gastric cancer, and the combined-clinical model showed the highest predictive efficiency. CRITICAL RELEVANCE STATEMENT: Intratumoral and peritumoral radiomics can noninvasively predict the pathological response against advanced gastric cancer after neoadjuvant chemotherapy to guide early treatment decision and provide individual treatment for patients. KEY POINTS: 1. Radiomics can predict pathological responses after neoadjuvant chemotherapy against advanced gastric cancer. 2. Peritumoral radiomics has additional predictive value. 3. Radiomics-clinical models can guide early treatment decisions and improve patient prognosis.

16.
Adv Sci (Weinh) ; 11(13): e2307242, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38247171

RESUMO

N6-methyladenosine (m6A) modification orchestrates cancer formation and progression by affecting the tumor microenvironment (TME). For hepatocellular carcinoma (HCC), immune evasion and angiogenesis are characteristic features of its TME. The role of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), as an m6A reader, in regulating HCC TME are not fully understood. Herein, it is discovered that trimethylated histone H3 lysine 4 and H3 lysine 27 acetylation modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis. Animal experiments demonstrated that Ythdf2 depletion inhibited spontaneous HCC formation, while its overexpression promoted xenografted HCC progression. Mechanistically, YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. Elevated ETV5 expression induced the transcription of programmed death ligand-1 and vascular endothelial growth factor A, thereby promoting HCC immune evasion and angiogenesis. Targeting YTHDF2 via small interference RNA-containing aptamer/liposomes successfully both inhibited HCC immune evasion and angiogenesis. Together, this findings reveal the potential application of YTHDF2 in HCC prognosis and targeted treatment.


Assuntos
Aptâmeros de Nucleotídeos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas de Ligação a RNA , Animais , Angiogênese , Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Evasão da Resposta Imune , Neoplasias Hepáticas/genética , Lisina , Fatores de Transcrição/metabolismo , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a DNA/metabolismo
17.
AIDS Patient Care STDS ; 38(1): 14-22, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38227279

RESUMO

Florida is one of the HIV epicenters with high incidence and marked sociodemographic disparities. We analyzed a decade of statewide electronic health record/claims data-OneFlorida+-to identify and characterize pre-exposure prophylaxis (PrEP) recipients and newly diagnosed HIV cases in Florida. Refined computable phenotype algorithms were applied and a total of 2186 PrEP recipients and 7305 new HIV diagnoses were identified between January 2013 and April 2021. We examined patients' sociodemographic characteristics, stratified by self-reported sex, along with both frequency-driven and expert-selected descriptions of clinical conditions documented within 12 months before the first PrEP use or HIV diagnosis. PrEP utilization rate increased in both sexes; higher rates were observed among males with sex differences widening in recent years. HIV incidence peaked in 2016 and then decreased with minimal sex differences observed. Clinical characteristics were similar between the PrEP and new HIV diagnosis cohorts, characterized by a low prevalence of sexually transmitted infections (STIs) and a high prevalence of mental health and substance use conditions. Study limitations include the overrepresentation of Medicaid recipients, with over 96% of female PrEP users on Medicaid, and the inclusion of those engaged in regular health care. Although PrEP uptake increased in Florida, and HIV incidence decreased, sex disparity among PrEP recipients remained. Screening efforts beyond individuals with documented prior STI and high-risk behavior, especially for females, including integration of mental health care with HIV counseling and testing, are crucial to further equalize PrEP access and improve HIV prevention programs.


Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Estados Unidos , Humanos , Feminino , Masculino , Florida/epidemiologia , Registros Eletrônicos de Saúde , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Demografia
18.
J Nutr Educ Behav ; 56(3): 173-183, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38244010

RESUMO

OBJECTIVE: Identify psychosocial factors influencing food waste mitigation and explore motivations and strategies for successful conservation among self-identified food conservers. METHODS: Mixed-methods study consisting of an online survey estimating food waste production and psychosocial factors and a focus group to explore waste mitigation strategies and motivations. RESULTS: Sampled 27 self-identified conservers (female, aged 18-30 years, White/Asian). Mean household food waste was 6.6 cups/wk (range, 0.0-97.9 cups/wk; median 1.3 cups). Reported waste mitigation strategies include proactive mitigation and adaptive recovery measures in each phase of the food management continuum. Conservers reported various intrinsic and extrinsic motivations to reduce food waste and viewed barriers as manageable. CONCLUSIONS AND IMPLICATIONS: Food conservers act on high intentions to reduce waste by consistently employing both proactive waste mitigation and adaptive food recovery measures. Future research is needed to determine if these findings hold in larger, more diverse samples and link specific behaviors to waste volume.


Assuntos
Alimentos , Eliminação de Resíduos , Feminino , Humanos , Inquéritos e Questionários
19.
Adv Mater ; 36(14): e2310584, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38160326

RESUMO

The properties of proton conductors determine the operating temperature range of fuel cells. Typically, phosphoric acid (PA) proton conductors exhibit excellent proton conductivity owing to their high proton dissociation and self-diffusion abilities. However, at low temperatures or high current densities, water-induced PA loss causes rapid degradation of cell performance. Maintaining efficient and stable proton conductivity within a flexible temperature range can significantly reduce the start-up temperature of PA-doped proton exchange membrane fuel cells. In this study, a dual-proton conductor composed of an organic phosphonic acid (ethylenediamine tetramethylene phosphonic acid, EDTMPA) and an inorganic PA is developed for proton exchange membranes. The proposed dual-proton conductor can operate within a flexible temperature range of 80-160 °C, benefiting from the strong interaction between EDTMPA and PA, and the enhanced proton dissociation. Fuel cells with the EDTMPA-PA dual-proton conductor showed excellent cell stability at 80 °C. In particular, under the high current density of 1.5 A cm-2 at 160 °C, the voltage decay rate of the fuel cell with the dual-proton conductor is one-thousandth of that of the fuel cell with PA-only proton conductor, indicating excellent stability.

20.
Front Psychiatry ; 14: 1258887, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38053538

RESUMO

Objective: Evidence suggests that high-quality health education and effective communication within the framework of social support hold significant potential in preventing postpartum depression. Yet, developing trustworthy and engaging health education and communication materials requires extensive expertise and substantial resources. In light of this, we propose an innovative approach that involves leveraging natural language processing (NLP) to classify publicly accessible lay articles based on their relevance and subject matter to pregnancy and mental health. Materials and methods: We manually reviewed online lay articles from credible and medically validated sources to create a gold standard corpus. This manual review process categorized the articles based on their pertinence to pregnancy and related subtopics. To streamline and expand the classification procedure for relevance and topics, we employed advanced NLP models such as Random Forest, Bidirectional Encoder Representations from Transformers (BERT), and Generative Pre-trained Transformer model (gpt-3.5-turbo). Results: The gold standard corpus included 392 pregnancy-related articles. Our manual review process categorized the reading materials according to lifestyle factors associated with postpartum depression: diet, exercise, mental health, and health literacy. A BERT-based model performed best (F1 = 0.974) in an end-to-end classification of relevance and topics. In a two-step approach, given articles already classified as pregnancy-related, gpt-3.5-turbo performed best (F1 = 0.972) in classifying the above topics. Discussion: Utilizing NLP, we can guide patients to high-quality lay reading materials as cost-effective, readily available health education and communication sources. This approach allows us to scale the information delivery specifically to individuals, enhancing the relevance and impact of the materials provided.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...