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1.
Eur Radiol ; 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38224375

RESUMO

OBJECTIVES: As a novel imaging marker, pericoronary fat attenuation index (FAI) reflects the local coronary inflammation which is one of the major mechanisms for in-stent restenosis (ISR). We aimed to validate the ability of pericoronary FAI to predict ISR in patients undergoing percutaneous coronary intervention (PCI). MATERIALS AND METHODS: Patients who underwent coronary CT angiography (CCTA) before PCI within 1 week between January 2017 and December 2019 at our hospital and had follow-up invasive coronary angiography (ICA) or CCTA were enrolled. Pericoronary FAI was measured at the site where stents would be placed. ISR was defined as ≥ 50% diameter stenosis at follow-up ICA or CCTA in the in-stent area. Multivariable analysis using mixed effects logistic regression models was performed to test the association between pericoronary FAI and ISR at lesion level. RESULTS: A total of 126 patients with 180 target lesions were included in the study. During 22.5 months of mean interval time from index PCI to follow-up ICA or CCTA, ISR occurred in 40 (22.2%, 40/180) stents. Pericoronary FAI was associated with a higher risk of ISR (adjusted OR = 1.12, p = 0.028). The optimum cutoff was - 69.6 HU. Integrating the dichotomous pericoronary FAI into current state of the art prediction model for ISR improved the prediction ability of the model significantly (△area under the curve = + 0.064; p = 0.001). CONCLUSION: Pericoronary FAI around lesions with subsequent stent placement is independently associated with ISR and could improve the ability of current prediction model for ISR. CLINICAL RELEVANCE STATEMENT: Pericoronary fat attenuation index can be used to identify the lesions with high risk for in-stent restenosis. These lesions may benefit from extra anti-inflammation treatment to avoid in-stent restenosis. KEY POINTS: • Pericoronary fat attenuation index reflects the local coronary inflammation. • Pericoronary fat attenuation index around lesions with subsequent stents placement can predict in-stent restenosis. • Pericoronary fat attenuation index can be used as a marker for future in-stent restenosis.

2.
Environ Sci Technol ; 58(23): 9980-9990, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38819024

RESUMO

Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother-infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53-15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.


Assuntos
Exposição Materna , Mecônio , Material Particulado , Humanos , Feminino , Mecônio/química , Gravidez , Estudos de Coortes , Recém-Nascido , Adulto , Poluentes Atmosféricos
3.
Macromol Rapid Commun ; : e2400087, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688322

RESUMO

The collapse or folding of an individual polymer chain into a nanoscale particle gives rise to single-chain nanoparticles (SCNPs), which share a soft nature with biological protein particles. The precise control of their properties, including morphology, internal structure, size, and deformability, are a long-standing and challenging pursuit. Herein, a new strategy based on amphiphilic alternating copolymers for producing SCNPs with ultrasmall size and uniform structure is presented. SCNPs are obtained by folding the designed alternating copolymer in N,N-dimethylformamide (DMF) and fixing it through a photocatalyzed cycloaddition reaction of anthracene units. Molecular dynamics simulation confirms the solvophilic outer corona and solvophobic inner core structure of SCNPs. Furthermore, by adjusting the length of PEG units, precise control over the mean size of SCNPs is achieved within the range of 2.8 to 3.9 nm. These findings highlight a new synthetic strategy that enables enhanced control over morphology and internal structure while achieving ultrasmall and uniform size for SCNPs.

4.
Phys Chem Chem Phys ; 26(7): 6180-6188, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38300128

RESUMO

The application of liquid crystal technology typically relies on the precise control of molecular orientation at a surface or interface. This control can be achieved through a combination of morphological and chemical methods. Consequently, variations in constrained boundary flexibility can result in a diverse range of phase behaviors. In this study, we delve into the self-assembly of liquid crystals within elastic spatial confinement by using the Gay-Berne model with the aid of molecular dynamics simulations. Our findings reveal that a spherical elastic shell promotes a more regular and orderly alignment of liquid crystals compared to a hard shell. Moreover, during the cooling process, the hard-shell confined system undergoes an isotropic-smectic phase transition. In contrast, the phase behavior within the spherical elastic shell closely mirrors the isotropic-nematic-smectic phase transition observed in bulk systems. This indicates that the orientational arrangement of liquid crystals and the deformations induced by a flexible interface engage in a competitive interplay during the self-assembly process. Importantly, we found that phase behavior could be manipulated by altering the flexibility of the confined boundaries. This insight offers a fresh perspective for the design of innovative materials, particularly in the realm of liquid crystal/polymer composites.

5.
Nature ; 562(7725): 91-95, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30209398

RESUMO

Owing to the unusual geometry of kagome lattices-lattices made of corner-sharing triangles-their electrons are useful for studying the physics of frustrated, correlated and topological quantum electronic states1-9. In the presence of strong spin-orbit coupling, the magnetic and electronic structures of kagome lattices are further entangled, which can lead to hitherto unknown spin-orbit phenomena. Here we use a combination of vector-magnetic-field capability and scanning tunnelling microscopy to elucidate the spin-orbit nature of the kagome ferromagnet Fe3Sn2 and explore the associated exotic correlated phenomena. We discover that a many-body electronic state from the kagome lattice couples strongly to the vector field with three-dimensional anisotropy, exhibiting a magnetization-driven giant nematic (two-fold-symmetric) energy shift. Probing the fermionic quasi-particle interference reveals consistent spontaneous nematicity-a clear indication of electron correlation-and vector magnetization is capable of altering this state, thus controlling the many-body electronic symmetry. These spin-driven giant electronic responses go well beyond Zeeman physics and point to the realization of an underlying correlated magnetic topological phase. The tunability of this kagome magnet reveals a strong interplay between an externally applied field, electronic excitations and nematicity, providing new ways of controlling spin-orbit properties and exploring emergent phenomena in topological or quantum materials10-12.

6.
Nutr Metab Cardiovasc Dis ; 34(2): 485-496, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38172006

RESUMO

BACKGROUND AND AIMS: Type 2 diabetes (T2DM) is a major cause of morbidity and mortality globally. Carnosine, a naturally occurring dipeptide, has anti-inflammatory, antioxidant, and anti-glycating effects, with preliminary evidence suggesting it may improve important chronic disease risk factors in adults with cardiometabolic conditions. METHODS AND RESULTS: In this randomised controlled trial, 43 adults (30%F) living with prediabetes or T2DM consumed carnosine (2 g) or a matching placebo daily for 14 weeks to evaluate its effect on glucose metabolism assessed via a 2-h 75 g oral glucose tolerance test. Secondary outcomes included body composition analysis by dual energy x-ray absorptiometry (DEXA), calf muscle density by pQCT, and anthropometry. Carnosine supplementation decreased blood glucose at 90 min (-1.31 mmol/L; p = 0.02) and 120 min (-1.60 mmol/L, p = 0.02) and total glucose area under the curve (-3.30 mmol/L; p = 0.04) following an oral glucose tolerance test. There were no additional changes in secondary outcomes. The carnosine group results remained significant before and after adjustment for age, sex, and change in weight (all>0.05), and in further sensitivity analyses accounting for missing data. There were no significant changes in insulin levels. CONCLUSION: This study provides preliminary support for larger trials evaluating carnosine as a potential treatment for prediabetes and the initial stages of T2DM. Likely mechanisms may include changes to hepatic glucose output explaining the observed reduction in blood glucose without changes in insulin secretion following carnosine supplementation.


Assuntos
Carnosina , Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Adulto , Humanos , Glicemia , Carnosina/uso terapêutico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Glucose , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/tratamento farmacológico
7.
Food Microbiol ; 122: 104553, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38839233

RESUMO

Biofilms formed by spoilage and pathogenic bacteria increase microbial persistence, causing an adverse influence on the quality of seafood. The mono-species biofilms are widely reported, however, the contamination of multi-species biofilms and their matrix in food environments are still not fully understood. Here, we assessed the contamination of multi-species biofilms in three seafood processing environments with different hygiene levels by detecting bacterial number and three biofilm matrix components (carbohydrates, extracellular DNA (eDNA), and proteins). Samples comprising seven food matrix surfaces and eight food processing equipment surfaces were collected from two seafood processing plants (XY and XC) and one seafood market (CC). The results showed that the bacterial counts ranged from 1.89 to 4.91 CFU/cm2 and 5.68 to 9.15 BCE/cm2 in these surfaces by cultivation and real-time PCR, respectively. Six biofilm hotspots were identified, including four in CC and two in XY. Among the three processing environments, the amplicon sequence variants (ASVs) of Proteobacteria, Bacteroidetes, and Actinobacteria decreased with improved processing hygiene, while Firmicutes showed a decrease in the four most abundant phyla. The most prevalent bacteria belonged to genera Psychrobacter, Acinetobacter, and Pseudomonas, demonstrating the significant differences and alteration in bacterial community composition during different environments. From the biofilm hotspots, 15 isolates with strong biofilm forming ability were identified, including 7 Pseudomonas, 7 Acinetobacter, and 1 Psychrobacter. The Pseudomonas isolates exhibited the highest production of EPS components and three strong motilities, whose characteristics were positively correlated. Thus, this study verified the presence of multi-species biofilms in seafood processing environments, offering preliminary insights into the diversity of microbial communities during processing. It highlights potential contamination sources and emphasizes the importance of understanding biofilms composition to control biofilms formation in seafood processing environments.


Assuntos
Bactérias , Biofilmes , Manipulação de Alimentos , Microbiologia de Alimentos , Microbiota , Alimentos Marinhos , Biofilmes/crescimento & desenvolvimento , Alimentos Marinhos/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/crescimento & desenvolvimento , Higiene , Contaminação de Alimentos/análise
8.
J Vis ; 24(6): 17, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38916886

RESUMO

A large body of literature has examined specificity and transfer of perceptual learning, suggesting a complex picture. Here, we distinguish between transfer over variations in a "task-relevant" feature (e.g., transfer of a learned orientation task to a different reference orientation) and transfer over a "task-irrelevant" feature (e.g., transfer of a learned orientation task to a different retinal location or different spatial frequency), and we focus on the mechanism for the latter. Experimentally, we assessed whether learning a judgment of one feature (such as orientation) using one value of an irrelevant feature (e.g., spatial frequency) transfers to another value of the irrelevant feature. Experiment 1 examined whether learning in eight-alternative orientation identification with one or multiple spatial frequencies transfers to stimuli at five different spatial frequencies. Experiment 2 paralleled Experiment 1, examining whether learning in eight-alternative spatial-frequency identification at one or multiple orientations transfers to stimuli with five different orientations. Training the orientation task with a single spatial frequency transferred widely to all other spatial frequencies, with a tendency to specificity when training with the highest spatial frequency. Training the spatial frequency task fully transferred across all orientations. Computationally, we extended the identification integrated reweighting theory (I-IRT) to account for the transfer data (Dosher, Liu, & Lu, 2023; Liu, Dosher, & Lu, 2023). Just as location-invariant representations in the original IRT explain transfer over retinal locations, incorporating feature-invariant representations effectively accounted for the observed transfer. Taken together, we suggest that feature-invariant representations can account for transfer of learning over a "task-irrelevant" feature.


Assuntos
Estimulação Luminosa , Humanos , Estimulação Luminosa/métodos , Adulto Jovem , Masculino , Percepção Visual/fisiologia , Adulto , Feminino , Transferência de Experiência/fisiologia , Aprendizagem/fisiologia , Orientação Espacial/fisiologia , Simulação por Computador , Orientação/fisiologia
9.
J Vis ; 24(5): 8, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38780934

RESUMO

Perceptual learning is a multifaceted process, encompassing general learning, between-session forgetting or consolidation, and within-session fast relearning and deterioration. The learning curve constructed from threshold estimates in blocks or sessions, based on tens or hundreds of trials, may obscure component processes; high temporal resolution is necessary. We developed two nonparametric inference procedures: a Bayesian inference procedure (BIP) to estimate the posterior distribution of contrast threshold in each learning block for each learner independently and a hierarchical Bayesian model (HBM) that computes the joint posterior distribution of contrast threshold across all learning blocks at the population, subject, and test levels via the covariance of contrast thresholds across blocks. We applied the procedures to the data from two studies that investigated the interaction between feedback and training accuracy in Gabor orientation identification over 1920 trials across six sessions and estimated learning curve with block sizes L = 10, 20, 40, 80, 160, and 320 trials. The HBM generated significantly better fits to the data, smaller standard deviations, and more precise estimates, compared to the BIP across all block sizes. In addition, the HBM generated unbiased estimates, whereas the BIP only generated unbiased estimates with large block sizes but exhibited increased bias with small block sizes. With L = 10, 20, and 40, we were able to consistently identify general learning, between-session forgetting, and rapid relearning and adaptation within sessions. The nonparametric HBM provides a general framework for fine-grained assessment of the learning curve and enables identification of component processes in perceptual learning.


Assuntos
Teorema de Bayes , Aprendizagem , Limiar Sensorial , Humanos , Aprendizagem/fisiologia , Limiar Sensorial/fisiologia , Percepção Visual/fisiologia , Sensibilidades de Contraste/fisiologia , Curva de Aprendizado , Estimulação Luminosa/métodos
10.
Nano Lett ; 23(3): 954-961, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36706049

RESUMO

In kagome lattice, with the emergence of Dirac cones and flat band in electronic structure, it provides a versatile ground for exploring intriguing interplay among frustrated geometry, topology and correlation. However, such engaging interest is strongly limited by available kagome materials in nature. Here we report on a synthetic strategy of constructing kagome systems via self-intercalation of Fe atoms into the van der Waals gap of FeSe2 via molecular beam epitaxy. Using low-temperature scanning tunneling microscopy, we unveil a kagome-like morphology upon intercalating a 2 × 2 ordered Fe atoms, resulting in a stoichiometry of Fe5Se8. Both the bias-dependent STM imaging and theoretical modeling calculations suggest that the kagome pattern mainly originates from slight but important reconstruction of topmost Se atoms, incurred by the nonequivalent subsurface Fe sites due to the intercalation. Our study demonstrates an alternative approach of constructing artificial kagome structures, which envisions to be tuned for exploring correlated quantum states.

11.
Infect Immun ; 91(5): e0010023, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37052497

RESUMO

Streptococcus pneumoniae relies on two-component systems (TCSs) to regulate the processes of pathogenicity, osmotic pressure, chemotaxis, and energy metabolism. The TCS01 system of S. pneumoniae is composed of HK01 (histidine kinase) and RR01 (response regulator). Previous studies have reported that an rr01 mutant reduced the pneumococcal virulence in rat pneumonia, bacteremia, a nasopharyngeal model, and infective endocarditis. However, the mechanism of TCS01 (HK/RR01) regulating pneumococcal virulence remains unclear. Here, pneumococcal mutant strains Δrr01, Δhk01, and Δrr01&hk01 were constructed, and bacterial adhesion and invasion to A549 cells were compared. RNA sequencing was performed in D39 wild-type and Δrr01 strains, and transcript profile changes were analyzed. Differentially expressed virulence genes in the Δrr01 strain were screened out and identified by quantitative real-time PCR (qRT-PCR). Our results showed that pneumococcal mutant strains exhibited attenuated adhesion and invasion to A549 cells and differential transcript profiles. Results of qRT-PCR identification showed that the differential virulence genes screened out were downregulated. Among those changed virulence genes in the Δrr01 strain, the downregulated expression level of choline binding protein pcpA was the most obvious. Complementation of rr01 and overexpression of pcpA in the Δrr01 strain partially restored both pneumococcal adhesion and invasion, and rr01 complementation made the expression of pcpA upregulated. These findings revealed that rr01 influenced pneumococcal virulence by regulating pcpA.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular , Infecções Pneumocócicas , Streptococcus pneumoniae , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidade , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Células A549 , Humanos , Infecções Pneumocócicas/metabolismo , Infecções Pneumocócicas/microbiologia , Aderência Bacteriana
12.
Radiology ; 308(2): e230124, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37606570

RESUMO

Background Lipid-rich plaques detected with intravascular imaging are associated with adverse cardiovascular events in patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS). But evidence about the prognostic implication of coronary CT angiography (CCTA) in NSTE ACS is limited. Purpose To assess whether quantitative variables at CCTA that reflect lipid content in nonrevascularized plaques in individuals with NSTE ACS might be predictors of subsequent nonrevascularized plaque-related major adverse cardiovascular events (MACEs). Materials and Methods In this multicenter prospective cohort study, from November 2017 to January 2019, individuals diagnosed with NSTE ACS (excluding those at very high risk) were enrolled and underwent CCTA before invasive coronary angiography (ICA) within 1 day. Lipid core was defined as areas with attenuation less than 30 HU in plaques. MACEs were defined as cardiac death, myocardial infarction, hospitalization for unstable angina, and revascularization. Participants were followed up at 6 months, 12 months, and annually thereafter for at least 3 years (ending by July 2022). Multivariable analysis using Cox proportional hazards regression models was performed to determine the association between lipid core burden, lipid core volume, and future nonrevascularized plaque-related MACEs at both the participant and plaque levels. Results A total of 342 participants (mean age, 57.9 years ± 11.1 [SD]; 263 male) were included for analysis with a median follow-up period of 4.0 years (IQR, 3.6-4.4 years). The 4-year nonrevascularized plaque-related MACE rate was 23.9% (95% CI: 19.1, 28.5). Lipid core burden (hazard ratio [HR], 12.6; 95% CI: 4.6, 34.3) was an independent predictor at the participant level, with an optimum threshold of 2.8%. Lipid core burden (HR, 12.1; 95% CI: 6.6, 22.3) and volume (HR, 11.0; 95% CI: 6.5, 18.4) were independent predictors at the plaque level, with an optimum threshold of 7.2% and 10.1 mm3, respectively. Conclusion In NSTE ACS, quantitative analysis of plaque lipid content at CCTA independently predicted participants and plaques at higher risk for future nonrevascularized plaque-related MACEs. Chinese Clinical Trial Registry no. ChiCTR1800018661 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Tavakoli and Duman in this issue.


Assuntos
Síndrome Coronariana Aguda , Angiografia por Tomografia Computadorizada , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Coronariana Aguda/diagnóstico por imagem , Angiografia Coronária , Estudos Prospectivos , Lipídeos
13.
Small ; 19(31): e2205291, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36635000

RESUMO

Fabricating polymer electrolyte membranes (PEMs) simultaneously with high ion conductivity and selectivity has always been an ultimate goal in many membrane-integrated systems for energy conversion and storage. Constructing broader ion-conducting channels usually enables high-efficient ion conductivity while often bringing increased crossover of other ions or molecules simultaneously, resulting in decreased selectivity. Here, the ultra-small carbon dots (CDs) with the selective barriers are self-assembled within proton-conducting channels of PEMs through electrostatic interaction to enhance the proton conductivity and selectivity simultaneously. The functional CDs regulate the nanophase separation of PEMs and optimize the hydration proton network enabling higher-efficient proton transport. Meanwhile, the CDs within proton-conducting channels prevent fuel from permeating selectively due to their repelling and spatial hindrance against fuel molecules, resulting in highly enhanced selectivity. Benefiting from the improved conductivity and selectivity, the open-circuit voltage and maximum power density of the direct methanol fuel cell (DMFC) equipped with the hybrid membranes raised by 23% and 93%, respectively. This work brings new insight to optimize polymer membranes for efficient and selective transport of ions or small molecules, solving the trade-off of conductivity and selectivity.

14.
J Transl Med ; 21(1): 851, 2023 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-38007511

RESUMO

BACKGROUND: The tumor microenvironment and intercellular communication between solid tumors and the surrounding stroma play crucial roles in cancer initiation, progression, and prognosis. Radiomics provides clinically relevant information from radiological images; however, its biological implications in uncovering tumor pathophysiology driven by cellular heterogeneity between the tumor and stroma are largely unknown. We aimed to identify radiogenomic signatures of cellular tumor-stroma heterogeneity (TSH) to improve breast cancer management and prognosis analysis. METHODS: This retrospective multicohort study included five datasets. Cell subpopulations were estimated using bulk gene expression data, and the relative difference in cell subpopulations between the tumor and stroma was used as a biomarker to categorize patients into good- and poor-survival groups. A radiogenomic signature-based model utilizing dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was developed to target TSH, and its clinical significance in relation to survival outcomes was independently validated. RESULTS: The final cohorts of 1330 women were included for cellular TSH biomarker identification (n = 112, mean age, 57.3 years ± 14.6) and validation (n = 886, mean age, 58.9 years ± 13.1), radiogenomic signature of TSH identification (n = 91, mean age, 55.5 years ± 11.4), and prognostic (n = 241) assessments. The cytotoxic lymphocyte biomarker differentiated patients into good- and poor-survival groups (p < 0.0001) and was independently validated (p = 0.014). The good survival group exhibited denser cell interconnections. The radiogenomic signature of TSH was identified and showed a positive association with overall survival (p = 0.038) and recurrence-free survival (p = 3 × 10-4). CONCLUSION: Radiogenomic signatures provide insights into prognostic factors that reflect the imbalanced tumor-stroma environment, thereby presenting breast cancer-specific biological implications and prognostic significance.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Estudos Retrospectivos , Perfilação da Expressão Gênica/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Tireotropina/genética , Microambiente Tumoral/genética
15.
Bioconjug Chem ; 34(1): 248-256, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36621834

RESUMO

Enzyme-responsive drug delivery systems have drawn much attention in the field of cancer theranostics due to their high sensitivity and substrate specificity under mild conditions. In this study, an amphiphilic polymer T1 is reported, which contains a tetraphenylethene unit and a poly(ethylene glycol) chain linked by an esterase-responsive phenolic ester bond. In aqueous solution, T1 formed stable micelles via self-assembly, which showed an aggregation-induced emission enhancement of 32-fold at 532 nm and a critical micelle concentration of 0.53 µM as well as esterase-responsive activity. The hydrophobic drug doxorubicin (DOX) was efficiently encapsulated into the micelles with a drug loading of 21%. In the presence of the esterase, the selective decomposition of drug-loaded T1 micelles was observed, and DOX was subsequently released with a half-life of 5 h. In vitro antitumor studies showed that T1@DOX micelles exhibited good therapeutic effects on HeLa cells, while normal cells remained mostly intact. In vivo anticancer experiments revealed that T1@DOX micelles indeed suppressed tumor growth and had reduced side effects compared to DOX·HCl. The present work showed the potential clinical application of esterase-responsive drug delivery in cancer therapy.


Assuntos
Micelas , Polietilenoglicóis , Humanos , Polietilenoglicóis/química , Células HeLa , Esterases , Portadores de Fármacos/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Polímeros/química , Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio
16.
Ann Surg Oncol ; 30(12): 7172-7180, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37543550

RESUMO

BACKGROUND: Surgery is the primary treatment for locally advanced differentiated thyroid cancer (DTC). However, some locally advanced patients are not candidates for R0/1 resection. There is limited evidence of neoadjuvant treatment in locally advanced DTC. Surufatinib targets multiple kinases, which is efficient, tolerable, and safe in patients with radioiodine-refractory DTC. In addition, surufatinib plus toripalimab (an anti-PD-1 antibody) showed encouraging antitumor activity in advanced solid tumors. This study was designed to evaluate the efficacy and safety of surufatinib plus toripalimab in locally advanced DTC in the neoadjuvant setting. METHODS: In this single-arm, phase II study, patients with pathologically confirmed unresectable or borderline resectable DTC were eligible and received a combination of 250 mg of surufatinib (orally daily) with 240 mg of toripalimab (intravenous, every 3 weeks). Treatment continued until satisfied for curative surgery, disease progression, withdrawal of consent, unacceptable toxicity, or investigator decision. Primary endpoint was objective response rate (ORR). Secondary endpoints included R0/1 resection rate, adverse events (AEs), etc. RESULTS: Ten patients were enrolled and received at least 4 cycles of treatment. The ORR was 60%. Nine patients received R0/1 resections after neoadjuvant treatment. The median best percentage change in the sum of the target lesion diameter was 32%. Most adverse events (AEs) were grade 1 or 2. CONCLUSIONS: Surufatinib in combination with toripalimab as neoadjuvant therapy for locally advanced DTC was feasible, and the majority of patients achieved R0/1 resection. It represents a new option for locally advanced DTC and needs further investigation.

17.
Analyst ; 148(10): 2214-2224, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37114554

RESUMO

Chlorpromazine (CPZ) is a medicine for nervous system disorders. Measuring CPZ in vivo can assist doctors in evaluating patients' blood drug concentration and monitoring drug metabolism. Therefore, an accurate in vivo detection of CPZ is crucial. In recent years, the acupuncture needle, traditionally used in Chinese medicine, has emerged as a potential electrode in the field of electrochemistry, with promising applications for in vivo detection. In this study, Au/Cu nanoparticles were electrodeposited onto an acupuncture needle electrode (ANE) to improve electrical conductivity and provide an electro-catalytic surface. Subsequently, 3-aminophenylboronic acid and CPZ were attracted to each other through intermolecular forces; at the same time, the interaction force of Au-S between CPZ and the AuNPs made the polymer layer grow around the CPZ molecules on the modified electrode surface. The imprinted nanocavities showed highly selective and sensitive detection performance for CPZ after elution. Inside the recognizable site and microenvironment of the cavities, the captured CPZ molecule provided a suitable configuration for the fluent electron transfer of the electroactive group within a short range from the Au/Cu bimetal. Under ideal conditions, the MIP/Au/Cu/ANE exhibited two good linear ranges of 0.1-100 µM and 100-1000 µM with a detection limit of 0.07 µM. Moreover, the sensors showed great selectivity, good stability and excellent repeatability, making them suitable for CPZ detection in human serum. This provides a novel idea for real-time and in vivo CPZ detection.


Assuntos
Terapia por Acupuntura , Técnicas Biossensoriais , Nanopartículas Metálicas , Impressão Molecular , Humanos , Clorpromazina , Ouro/química , Cobre/química , Nanopartículas Metálicas/química , Limite de Detecção , Eletrodos , Técnicas Eletroquímicas
18.
J Oral Pathol Med ; 52(5): 389-401, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36153671

RESUMO

BACKGROUND: Lymph node metastasis can independently predict oral squamous cell carcinoma patients' survival. This study would investigate the genetic and cellular differences between oral squamous cell carcinoma with positive and negative lymph node metastases. METHODS: We gathered single-cell RNA sequencing and bulk gene expression data from the Cancer Genome Atlas and Gene Expression Omnibus databases. Sixty lymph node-metastasis-related genes were discovered with refined single-cell RNA sequencing data analysis, and consensus clustering provided three molecular subtypes of oral squamous cell carcinoma. Least absolute shrinkage and selection operator analyses were then utilized to establish a five-gene risk model. CIBERSORT analysis revealed the immune infiltration profile of different risk subgroups. RESULTS: Oral squamous cell carcinoma patients were classified into three subtypes based on the 60 lymph node-metastasis-related key genes identified by single-cell RNA sequencing data. Patients in Subtype 3 showed a tendency for lymph node metastasis and poorer prognosis. Moreover, five biomarkers were selected from the 60 genes to construct a five-gene risk model evaluating the risk of lymph node metastasis. A lower probability of lymph node metastasis and a better prognosis was observed in the low-risk group. The immune infiltration of three different risk groups was explored with CIBERSORT. Besides, further analysis implied different sensitivities of anticancer drugs, including immunotherapy drugs and targeted compounds, in the three risk groups. CONCLUSION: In view of intratumoral heterogeneity, we found 60 genes associated with lymph node metastasis of oral squamous cell carcinoma. Subsequently, we constructed a five-gene signature that could improve the prediction of lymph node metastasis, clinical outcome, and promote individualized treatment strategies for oral squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Metástase Linfática/genética , Prognóstico , RNA-Seq
19.
Appl Microbiol Biotechnol ; 107(1): 313-326, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36414759

RESUMO

Vibrio parahaemolyticus (VP) as a prominent foodborne pathogen in seafood generally adheres to various surfaces and forms biofilms in the processing of aquatic products. The study aimed to elucidate the inhibitory efficacy and potential mechanism of salinity (NaCl) or it combined with citral against the biofilm formation of VP. Three VP strains formed the most biofilm at 1.0% NaCl, and their biofilms gradually declined with the increase of NaCl concentration. Compared with 1% NaCl, applying 3% and 5% NaCl or NaCl in combination with citral at 10-40 µg/mL significantly reduced biofilm biomass, cellular activity, and viable cells, as well as extracellular polymeric substances (EPS) and cell surface hydrophobicity. Sparser and thinner VP biofilm with large dead cells were observed under the combined treatment, in contrast to the dense architectures of biofilm formed at 1% NaCl. Although VP exhibited the strongest swimming and swarming ability at 3% NaCl, the two motilities were both significantly reduced by citral for all three salinities. Transcriptomic profiling revealed that, compared with 1% NaCl (Con), the two treatments consisting of 3% NaCl (Sal3) and it combined with 40 µg/mL citral (Com) drastically altered gene expression patterns in VP biofilm cells, resulting in 1196 and 1304 differentially expressed genes, respectively. The treatment of Com group altered the transcription of various genes related to chemotaxis, flagellar assembly, EPS synthesis, LuxS and CqsA-mediated quorum sensing, and c-di-GMP, which might interfere with biofilm development of VP. Our findings provided novel insights into the combined regulatory mechanism of high salinity and citral for antibiofilm formation in VP. KEY POINTS: • High salinity enhanced the antibiofilm efficacy of citral against Vibrio parahaemolyticus. • Combined treatment downregulated the expression of exopolysaccharide synthesis genes. • A total of 3% NaCl and combined treatments interfered with signaling pathways of QS and c-di-GMP.


Assuntos
Vibrio parahaemolyticus , Vibrio parahaemolyticus/genética , Cloreto de Sódio/farmacologia , Transcriptoma , Percepção de Quorum/genética , Biofilmes
20.
J Chem Phys ; 159(12)2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-38127373

RESUMO

How to fabricate perpendicularly oriented domains (PODs) of lamellar and cylinder phases in block copolymer thin films remains a major challenge. In this work, via a coarse-grained molecular dynamics simulation study, we report a solvent evaporation strategy starting from a mixed solution of A-b-B-type diblock copolymers (DBCs) and single-chain nanoparticles (SCNPs) with the same composition, which is capable of spontaneously generating PODs in drying DBC films induced by the interface segregation of SCNPs. The latter occurs at both the free surface and substrate and, consequently, neutralizes the interface selectivity of distinct blocks in DBCs, leading to spontaneous formation of PODs at both interfaces. The interface segregation of SCNPs is related to the weak solvophilicity of the internal cross-linker units. A mean-field theory calculation demonstrates that the increase in the chemical potential of SCNPs in the bulk region drives their interface segregation along with solvent evaporation. We believe that such a strategy can be useful in regulating the PODs of DBC films in practical applications.

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