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1.
Cereb Cortex ; 34(3)2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38436466

RESUMEN

The debate on whether computer gaming enhances players' cognitive function is an ongoing and contentious issue. Aiming to delve into the potential impacts of computer gaming on the players' cognitive function, we embarked on a brain imaging-derived phenotypes (IDPs)-wide Mendelian randomization (MR) study, utilizing publicly available data from a European population. Our findings indicate that computer gaming has a positive impact on fluid intelligence (odds ratio [OR] = 6.264, P = 4.361 × 10-10, 95% confidence interval [CI] 3.520-11.147) and cognitive function (OR = 3.322, P = 0.002, 95% CI 1.563-7.062). Out of the 3062 brain IDPs analyzed, only one phenotype, IDP NET100 0378, was significantly influenced by computer gaming (OR = 4.697, P = 1.10 × 10-5, 95% CI 2.357-9.361). Further MR analysis suggested that alterations in the IDP NET100 0378 caused by computer gaming may be a potential factor affecting fluid intelligence (OR = 1.076, P = 0.041, 95% CI 1.003-1.153). Our MR study lends support to the notion that computer gaming can facilitate the development of players' fluid intelligence by enhancing the connectivity between the motor cortex in the resting-state brain and key regions such as the left dorsolateral prefrontal cortex and the language center.


Asunto(s)
Análisis de la Aleatorización Mendeliana , Juegos de Video , Encéfalo/diagnóstico por imagen , Cognición , Computadores , Inteligencia , Fenotipo , Neuroimagen
2.
Nano Lett ; 23(11): 5123-5130, 2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37272668

RESUMEN

Developing cost-effective and highly efficient photocathodes toward polysulfide redox reduction is highly desirable for advanced quantum dot (QD) photovoltaics. Herein, we demonstrate nitrogen doped carbon (N-C) shell-supported iron single atom catalysts (Fe-SACs) capable of catalyzing polysulfide reduction in QD photovoltaics for the first time. Specifically, Fe-SACs with FeN4 active sites feature a power conversion efficiency of 13.7% for ZnCuInSe-QD photovoltaics (AM1.5G, 100 mW/cm2), which is the highest value for ZnCuInSe QD-based photovoltaics, outperforming those of Cu-SACs and N-C catalysts. Compared with N-C, Fe-SACs exhibit suitable energy level matching with polysulfide redox couples, revealed by the Kelvin probe force microscope, which accelerates the charge transferring at the interfaces of catalyst/polysulfide redox couple. Density functional theory calculations demonstrate that the outstanding catalytic activity of Fe-SACs originates from the preferable adsorption of S42- on the FeN4 active sites and the high activation degree of the S-S bonds in S42- initiated by the FeN4 active sites.

3.
PLoS Pathog ; 17(3): e1009481, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33788895

RESUMEN

TcpC is a virulence factor of uropathogenic E. coli (UPEC). It was found that TIR domain of TcpC impedes TLR signaling by direct association with MyD88. It has been a long-standing question whether bacterial pathogens have evolved a mechanism to manipulate MyD88 degradation by ubiquitin-proteasome pathway. Here, we show that TcpC is a MyD88-targeted E3 ubiquitin ligase. Kidney macrophages from mice with pyelonephritis induced by TcpC-secreting UPEC showed significantly decreased MyD88 protein levels. Recombinant TcpC (rTcpC) dose-dependently inhibited protein but not mRNA levels of MyD88 in macrophages. Moreover, rTcpC significantly promoted MyD88 ubiquitination and accumulation in proteasomes in macrophages. Cys12 and Trp106 in TcpC are crucial amino acids in maintaining its E3 activity. Therefore, TcpC blocks TLR signaling pathway by degradation of MyD88 through ubiquitin-proteasome system. Our findings provide not only a novel biochemical mechanism underlying TcpC-medicated immune evasion, but also the first example that bacterial pathogens inhibit MyD88-mediated signaling pathway by virulence factors that function as E3 ubiquitin ligase.


Asunto(s)
Proteínas de Escherichia coli/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Transducción de Señal/fisiología , Escherichia coli Uropatógena/patogenicidad , Factores de Virulencia/metabolismo , Animales , Línea Celular , Femenino , Humanos , Evasión Inmune/fisiología , Macrófagos , Ratones , Ratones Endogámicos C57BL , Pielonefritis/inmunología , Pielonefritis/microbiología , Receptores Toll-Like/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Escherichia coli Uropatógena/inmunología , Escherichia coli Uropatógena/metabolismo , Virulencia/fisiología
4.
Mar Drugs ; 21(4)2023 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-37103356

RESUMEN

Aeruginosins, a family of nonribosomal linear tetrapeptides discovered from cyanobacteria and sponges, exhibit in vitro inhibitory activity on various types of serine proteases. This family is characterized by the existence of the 2-carboxy-6-hydroxy-octahydroindole (Choi) moiety occupied at the central position of the tetrapeptide. Aeruginosins have attracted much attention due to their special structures and unique bioactivities. Although many studies on aeruginosins have been published, there has not yet been a comprehensive review that summarizes the diverse research ranging from biogenesis, structural characterization and biosynthesis to bioactivity. In this review, we provide an overview of the source, chemical structure as well as spectrum of bioactivities of aeruginosins. Furthermore, possible opportunities for future research and development of aeruginosins were discussed.


Asunto(s)
Productos Biológicos , Cianobacterias , Péptidos , Péptidos/química , Productos Biológicos/química
5.
Parasitol Res ; 122(7): 1567-1572, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37212833

RESUMEN

Mites serve as pathogens, allergens, or microbial containers, which can seriously damage the health of humans and animals. The substantial amount of mite species and their similar morphology make it complicated to identify and classify. Our mouse breeder incidentally noticed papular-type erythema with itching and peeling of the skin in several places, and an investigation revealed that this symptom was caused by an uncommon parasite that appeared on the skin and around the nest of the mice. By morphological observation, DNA extraction, PCR amplification, and DNA sequencing, we roughly identified the category of the parasite as a mite. Then, we designed a specific primer cox1, amplified and sequenced the mitochondrial cox1 gene fragment of the mite, calculated the intraspecific and interspecific differences, and reconstructed the phylogenetic tree for sequence alignment. Finally, this species was identified and named this Ornithonyssus bacoti-KF. According to the ivermectin gradient test, we found that 0.1 mg/mL concentration of ivermectin solution was the most effective for mite removal in the bath, with no recurrence after 6 months of treatment. Ornithonyssus bacoti, diagnosed by microscopic exam and confirmed by PCR amplification sequencing, was treated with ivermectin to control the rodent-borne parasite effectively.


Asunto(s)
Infestaciones por Ácaros , Ácaros , Humanos , Animales , Ratones , Infestaciones por Ácaros/diagnóstico , Infestaciones por Ácaros/tratamiento farmacológico , Infestaciones por Ácaros/parasitología , Ivermectina , Filogenia , Piel
6.
Int J Mol Sci ; 24(5)2023 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-36901796

RESUMEN

The water-to-land transition is one of the most important events in evolutionary history of vertebrates. However, the genetic basis underlying many of the adaptations during this transition remains unclear. Mud-dwelling gobies in the subfamily Amblyopinae are one of the teleosts lineages that show terrestriality and provide a useful system for clarifying the genetic changes underlying adaptations to terrestrial life. Here, we sequenced the mitogenome of six species in the subfamily Amblyopinae. Our results revealed a paraphyletic origin of Amblyopinae with respect to Oxudercinae, which are the most terrestrial fishes and lead an amphibious life in mudflats. This partly explains the terrestriality of Amblyopinae. We also detected unique tandemly repeated sequences in the mitochondrial control region in Amblyopinae, as well as in Oxudercinae, which mitigate oxidative DNA damage stemming from terrestrial environmental stress. Several genes, such as ND2, ND4, ND6 and COIII, have experienced positive selection, suggesting their important roles in enhancing the efficiency of ATP production to cope with the increased energy requirements for life in terrestrial environments. These results strongly suggest that the adaptive evolution of mitochondrial genes has played a key role in terrestrial adaptions in Amblyopinae, as well as in Oxudercinae, and provide new insights into the molecular mechanisms underlying the water-to-land transition in vertebrates.


Asunto(s)
Genoma Mitocondrial , Perciformes , Animales , Perciformes/genética , Adaptación Fisiológica , Ecosistema , Agua , Filogenia
7.
Socioecon Plann Sci ; 85: 101430, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36093279

RESUMEN

After the outbreak of COVID-19, the freight demand fell briefly, and as production resumed, the trucking share rate increased again, further increasing energy consumption and environmental pollution. To optimize the sudden changing freight structure, the study aims on developing an evolution model based on Markov's theory to estimate the freight structure post-COVID-19. The current study applies economic cybernetics to establish a freight structural adjustment path optimization model and solve the problem of how much freight transportation should increase each year under the premise that the total turnover of the freight industry continues to grow, and how many years it will take at least to reach a reasonable freight structure. The freight transport structure of China is used to examine the feasibility of the proposed model. The finding indicates that the development of China's freight transport structure is at an adjustment period and should enter a stable period by 2035 and the COVID-19 makes it harder to adjust the freight structure. Increasing the growth rate of the freight volume of railway and waterway transportation is the key to realizing the optimization of the freight structure, and the freight structure path optimization method can realize the rationalization of the freight structure in advance.

8.
Sensors (Basel) ; 22(14)2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35891100

RESUMEN

Although increasing evidences support the notion that psychiatric disorders are associated with abnormal communication between brain regions, scattered studies have investigated brain electrophysiological disconnectivity of patients with generalized anxiety disorder (GAD). To this end, this study intends to develop an analysis framework for automatic GAD detection through incorporating multidimensional EEG feature extraction and machine learning techniques. Specifically, resting-state EEG signals with a duration of 10 min were obtained from 45 patients with GAD and 36 healthy controls (HC). Then, an analysis framework of multidimensional EEG characteristics (including univariate power spectral density (PSD) and fuzzy entropy (FE), and multivariate functional connectivity (FC), which can decode the EEG information from three different dimensions) were introduced for extracting aberrated multidimensional EEG features via statistical inter-group comparisons. These aberrated features were subsequently fused and fed into three previously validated machine learning methods to evaluate classification performance for automatic patient detection. We showed that patients exhibited a significant increase in beta rhythm and decrease in alpha1 rhythm of PSD, together with the reduced long-range FC between frontal and other brain areas in all frequency bands. Moreover, these aberrated features contributed to a very good classification performance with 97.83 ± 0.40% of accuracy, 97.55 ± 0.31% of sensitivity, 97.78 ± 0.36% of specificity, and 97.95 ± 0.17% of F1. These findings corroborate previous hypothesis of disconnectivity in psychiatric disorders and further shed light on distribution patterns of aberrant spatio-spectral EEG characteristics, which may lead to potential application of automatic diagnosis of GAD.


Asunto(s)
Electroencefalografía , Aprendizaje Automático , Trastornos de Ansiedad/diagnóstico , Encéfalo , Electroencefalografía/métodos , Entropía , Humanos
9.
Sensors (Basel) ; 22(20)2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-36298387

RESUMEN

Mental fatigue is a widely studied topic on account of its serious negative effects. But how the neural mechanism of task switching before and after mental fatigue remains a question. To this end, this study aims to use brain functional network features to explore the answer to this question. Specifically, task-state EEG signals were recorded from 20 participants. The tasks include a 400-s 2-back-task (2-BT), followed by a 6480-s of mental arithmetic task (MAT), and then a 400-s 2-BT. Network features and functional connections were extracted and analyzed based on the selected task switching states, referred to from Pre_2-BT to Pre_MAT before mental fatigue and from Post_MAT to Post_2-BT after mental fatigue. The results showed that mental fatigue has been successfully induced by long-term MAT based on the significant changes in network characteristics and the high classification accuracy of 98% obtained with Support Vector Machines (SVM) between Pre_2-BT and Post_2-BT. when the task switched from Pre_2-BT to Pre_MAT, delta and beta rhythms exhibited significant changes among all network features and the selected functional connections showed an enhanced trend. As for the task switched from Post_MAT to Post_2-BT, the network features and selected functional connectivity of beta rhythm were opposite to the trend of task switching before mental fatigue. Our findings provide new insights to understand the neural mechanism of the brain in the process of task switching and indicate that the network features and functional connections of beta rhythm can be used as neural markers for task switching before and after mental fatigue.


Asunto(s)
Electroencefalografía , Fatiga Mental , Humanos , Electroencefalografía/métodos , Encéfalo , Mapeo Encefálico , Máquina de Vectores de Soporte
10.
Entropy (Basel) ; 24(3)2022 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-35327935

RESUMEN

Offline hand-drawn diagram recognition is concerned with digitizing diagrams sketched on paper or whiteboard to enable further editing. Some existing models can identify the individual objects like arrows and symbols, but they become involved in the dilemma of being unable to understand a diagram's structure. Such a shortage may be inconvenient to digitalization or reconstruction of a diagram from its hand-drawn version. Other methods can accomplish this goal, but they live on stroke temporary information and time-consuming post-processing, which somehow hinders the practicability of these methods. Recently, Convolutional Neural Networks (CNN) have been proved that they perform the state-of-the-art across many visual tasks. In this paper, we propose DrawnNet, a unified CNN-based keypoint-based detector, for recognizing individual symbols and understanding the structure of offline hand-drawn diagrams. DrawnNet is designed upon CornerNet with extensions of two novel keypoint pooling modules which serve to extract and aggregate geometric characteristics existing in polygonal contours such as rectangle, square, and diamond within hand-drawn diagrams, and an arrow orientation prediction branch which aims to predict which direction an arrow points to through predicting arrow keypoints. We conducted wide experiments on public diagram benchmarks to evaluate our proposed method. Results show that DrawnNet achieves 2.4%, 2.3%, and 1.7% recognition rate improvements compared with the state-of-the-art methods across benchmarks of FC-A, FC-B, and FA, respectively, outperforming existing diagram recognition systems on each metric. Ablation study reveals that our proposed method can effectively enable hand-drawn diagram recognition.

11.
J Infect Dis ; 224(4): 620-631, 2021 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-33864371

RESUMEN

BACKGROUND: We investigatedthe association between time-averaged area under the curve (AAUC) of cytomegalovirus (CMV) viral load (VL) by day 100 and overall survival (OS) at 1-year after hematopoietic cell transplantation (HCT). METHODS: In a retrospective cohort study, including patients receiving HCT between June 2010 and December 2017 from Memorial Sloan Kettering Cancer Center, AAUC was calculated for patients with detected VL. Patients were categorized into non-controllers (Q4) and controllers (Q1-Q3) using the highest AAUC quartile as cutoff. Cox models were used to estimate the association between AAUC and OS. Patients with non-detected CMV VL were categorized into elite-controllers (recipient+ [R+] or R-/donor+ [D+]) and R-/D-. RESULTS: The study (N = 952) included 282 controllers, 93 non-controllers, 275 elite-controllers, and 302 R-/D-. OS was 80.1% and 58.1% for controllers and non-controllers, respectively. In multivariable models, non-controllers had worse OS versus controllers (adjusted hazard ratio [HR] = 2.65; 95% confidence interval [CI], 1.71-4.12). In landmark analyses, controllers had similar OS as elite-controllers (HR = 1.26; 95% CI, .83-1.91) or R-/D- (HR = 0.98; 95% CI, .64-1.5). CONCLUSIONS: Non-controllers had worse OS 1-year post-HCT. Controllers had similar OS as elite-controllers or R-/D-. Future studies are needed to validate our AAUC cutoff across different cohorts and CMV management strategies.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Insuficiencia Multiorgánica/mortalidad , Carga Viral , Citomegalovirus , Infecciones por Citomegalovirus/mortalidad , Humanos , Cinética , Insuficiencia Multiorgánica/virología , Estudios Retrospectivos , Tasa de Supervivencia
12.
J Infect Dis ; 222(7): 1180-1187, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32374872

RESUMEN

BACKGROUND: We report on predictors of adenovirus (ADV) viremia and correlation of ADV viral kinetics with mortality in ex vivo T-cell depleted (TCD) hematopoietic cell transplant (HCT). METHODS: T cell-depleted HCT recipients from January 1, 2012 through September 30, 2018 were prospectively monitored for ADV in the plasma through Day (D) +100 posttransplant or for 16 weeks after the onset of ADV viremia. Adenovirus viremia was defined as ≥2 consecutive viral loads (VLs) ≥1000 copies/mL through D +100. Time-averaged area under the curve (AAUC) or peak ADV VL through 16 weeks after onset of ADV viremia were explored as predictors of mortality in Cox models. RESULTS: Of 586 patients (adult 81.7%), 51 (8.7%) developed ADV viremia by D +100. Age <18 years, recipient cytomegalovirus seropositivity, absolute lymphocyte count <300 cells/µL at D +30, and acute graft-versus-host disease were predictors of ADV viremia in multivariate models. Fifteen (29%) patients with ADV viremia died by D +180; 8 of 15 (53%) died from ADV. Peak ADV VL (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.52-3.33) and increasing AAUC (HR, 2.95; 95% CI, 1.83-4.75) correlated with mortality at D +180. CONCLUSIONS: In TCD HCT, peak ADV VL and ADV AAUC correlated with mortality at D +180. Our data support the potential utility of ADV viral kinetics as endpoints in clinical trials of ADV therapies.


Asunto(s)
Infecciones por Adenoviridae/mortalidad , Trasplante de Células Madre Hematopoyéticas , Depleción Linfocítica , Linfocitos T/inmunología , Acondicionamiento Pretrasplante , Viremia/mortalidad , Adenoviridae/crecimiento & desarrollo , Infecciones por Adenoviridae/inmunología , Adolescente , Adulto , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/virología , Enfermedades Hematológicas/inmunología , Enfermedades Hematológicas/mortalidad , Enfermedades Hematológicas/virología , Humanos , Cinética , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Análisis de Supervivencia , Linfocitos T/trasplante , Trasplante Homólogo , Carga Viral , Viremia/inmunología
13.
Biol Blood Marrow Transplant ; 26(10): 1937-1947, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32640313

RESUMEN

Cytomegalovirus (CMV) viremia occurs in 40% to 80% of CMV-seropositive (R+) recipients of allogeneic hematopoietic cell transplantation (HCT). The preemptive therapy (PET) strategy has reduced the risk of CMV end-organ disease (EOD) and associated mortality but may lead to substantial healthcare resource utilization (HCRU) and costs. Real-world data on the economic impact of PET is relevant for the evaluation of alternative strategies for CMV management. We examined the impact of clinically significant CMV treated with PET on inpatient length of stay (LOS), number of readmissions, and associated costs from day 0 through day 180 post-HCT. This was a retrospective study of R+ adults who underwent peripheral blood or marrow allogeneic HCT at Memorial Sloan Kettering Cancer Center between March 2013 and December 2017. Patients were routinely screened for CMV by qPCR and received PET according to institutional standards of care. Data were extracted from electronic medical records and hospital databases. Itemized cost data per patient were obtained from the Vizient database, adjusted to 2017 dollars using inflation indices. Study outcomes included HCRU evaluated by inpatient LOS and inpatient cost in patients who received PET for clinically significant CMV (PET group) compared with those who did not receive PET (no PET group) and the frequency and cost of CMV-related readmissions compared with non CMV-related readmissions. We used generalized linear models to examine the incremental HCRU and costs associated with PET controlling for other potential factors. Of 357 patients, PET was initiated in 208 (58.3%), at a median of 35 days after HCT. By day 180, 23 patients (6.4%) had developed CMV EOD and 3 (.8%) had died of CMV. Compared with the no PET group, the PET group had a longer LOS for HCT admission (P = .0276), longer total LOS by day 180 (P = .0001), a higher number of readmissions (P = .0001), a higher mean inpatient cost for HCT admission ($189,389 versus $151,646; P = .0133), and a higher total inpatient cost ($297,563 versus $205,815; P < .0001). Among PET recipients, CMV-related readmissions were associated with higher mean cost per episode compared with non CMV-related readmissions ($165,455 versus $89,419; P = .005). CMV-related readmissions comprised 40.6% of total all-cause readmissions and incurred 55.9% of total all-cause readmission costs in PET recipients. Our data show that patients treated with currently available PET had greater inpatient HCRU and cost, by day 180 compared with patients who did not receive PET. The cost of CMV-related readmissions accounted for 56% of total readmission cost among PET recipients. Future studies are needed to examine the cost-effectiveness of alternative strategies for CMV management.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Adulto , Antivirales/uso terapéutico , Citomegalovirus , Infecciones por Citomegalovirus/tratamiento farmacológico , Hospitalización , Humanos , Estudios Retrospectivos
14.
Biol Blood Marrow Transplant ; 26(8): 1482-1491, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32315708

RESUMEN

(Val)ganciclovir (vGCV) or foscarnet (FCN) as preemptive therapy (PET) for cytomegalovirus (CMV) after allogeneic hematopoietic cell transplantation (HCT) is associated with myelosuppression and nephrotoxicity, respectively. We analyzed a cohort of CMV-seropositive (R+) HCT recipients managed preemptively at a single center. The objectives of our study were to (1) quantify the frequencies of neutropenia and acute kidney injury (AKI) through day +100 (D100) post-HCT and at PET discontinuation and (2) assess the impact of PET on neutropenia and AKI in multivariate models. This was a retrospective cohort study of adult CMV R+ recipients who underwent allo-HCT at Memorial Sloan Kettering Cancer Center from March 18, 2013, through December 31, 2017, and were managed with PET. Patients were grouped by receipt of PET (PET and no PET). Neutropenia and AKI were defined by Common Terminology Criteria for Adverse Events version 4. Frequencies of toxicities by D100 were compared between relevant groups. The impact of PET on toxicities was examined in univariate and multivariate Poisson/negative binomial regression models. Of 368 CMV R+ HCT recipients, 208 (56.5%) received PET. Neutropenia by D100 occurred in 41.8% and 28.6% patients in PET and no PET, respectively (P = .0009). PET increased the risk of neutropenia (adjusted relative risk = 1.81; 95% confidence interval [CI], 1.48 to 2.21; P < .0001) in multivariate analyses. AKI by D100 occurred in 12.0% and 7.8% patients in PET and no PET, respectively (P = .19). PET increased the risk of AKI by 2.75-fold (95% CI, 1.71 to 4.42; P < .0001). When PET recipients were grouped by first antiviral, neutropenia by D100 occurred in 34.8% and 48.9% of vGCV and FCN recipients, respectively, (P = .08), and AKI occurred in 13.0% and 34.0% of vGCV and FCN recipients, respectively (P = .001). At discontinuation of vGCV or FCN, neutropenia was present in 11.2% versus 2.1% patients, respectively (P = .08), and AKI was present in 1.9% of versus 12.8% patients respectively (P = .005). Preemptive therapy for CMV increased the risk of neutropenia and AKI in the first 100 days post-HCT by 1.8-fold and 2.8-fold, respectively. Our results underscore the need for safer antivirals for CMV management in HCT recipients.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Adulto , Antivirales/efectos adversos , Estudios de Cohortes , Citomegalovirus , Infecciones por Citomegalovirus/tratamiento farmacológico , Ganciclovir/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estudios Retrospectivos
15.
Org Biomol Chem ; 16(16): 3026-3037, 2018 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-29634066

RESUMEN

A biomimetic synthetic strategy and combinatorial chemistry were used to synthesize 34 novel monoterpenoid indole alkaloid (MIA) analogues, and their cytotoxic activities against five cancer cell lines (SW-480, A-549, HL-60, SMMC-7721, and MCF-7) were determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Fourteen of these analogues (7, 16-18, and 23-32) showed significantly greater inhibition of tumour cell proliferation than cisplatin. Compounds 17 and 18 showed the highest cytotoxic activity against the HL-60 cell line with IC50 values of 0.90 µM and 0.43 µM, respectively. Compound 18 slightly induced apoptosis and arrested the cell cycle in SW-480, A-549, HL-60, SMMC-7721, and MCF-7 cells. Analysis of the primary structure-activity relationships reveals that the introduction of different substituent groups at the C-3, C-5, and C-6 positions of the indole moiety and the C-10 position of the genipin moiety might have an effect on the antitumour activity of the resulting compounds.


Asunto(s)
Antineoplásicos , Alcaloides de Triptamina Secologanina/análogos & derivados , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Alcaloides de Triptamina Secologanina/síntesis química , Alcaloides de Triptamina Secologanina/farmacología , Relación Estructura-Actividad
16.
BMC Med Inform Decis Mak ; 18(1): 134, 2018 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-30558581

RESUMEN

BACKGROUND: Breast cancer chemoprevention can reduce breast cancer incidence in high-risk women; however, chemoprevention is underutilized in the primary care setting. We conducted a pilot study of decision support tools among high-risk women and their primary care providers (PCPs). METHODS: The intervention included a decision aid (DA) for high-risk women, RealRisks, and a provider-centered tool, Breast Cancer Risk Navigation (BNAV). Patients completed validated surveys at baseline, after RealRisks and after their PCP clinical encounter or at 6-months. Referral for high-risk consultation and chemoprevention uptake were assessed via the electronic health record. The primary endpoint was accuracy of breast cancer risk perception at 6-months. RESULTS: Among 40 evaluable high-risk women, median age was 64.5 years and median 5-year breast cancer risk was 2.19%. After exposure to RealRisks, patients demonstrated an improvement in accurate breast cancer risk perceptions (p = 0.02), an increase in chemoprevention knowledge (p < 0.01), and 24% expressed interest in taking chemoprevention. Three women had a high-risk referral, and no one initiated chemoprevention. Decisional conflict significantly increased from after exposure to RealRisks to after their clinical encounter or at 6-months (p < 0.01). Accurate breast cancer risk perceptions improved and was sustained at 6-months or after clinical encounters. We discuss the side effect profile of chemoprevention and the care pathway when RealRisks was introduced to understand why patients experienced increased decision conflict. CONCLUSION: Future interventions should carefully link the use of a DA more proximally to the clinical encounter, investigate timed measurements of decision conflict and improve risk communication, shared decision making, and chemoprevention education for PCPs. Additional work remains to better understand the impact of decision aids targeting both patients and providers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02954900 November 4, 2016 Retrospectively registered.


Asunto(s)
Neoplasias de la Mama/prevención & control , Quimioprevención , Toma de Decisiones Clínicas , Toma de Decisiones , Técnicas de Apoyo para la Decisión , Conocimientos, Actitudes y Práctica en Salud , Atención Primaria de Salud , Medición de Riesgo , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Proyectos Piloto
17.
Diagnostics (Basel) ; 14(11)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38893648

RESUMEN

Current assessments for generalized anxiety disorder (GAD) are often subjective and do not rely on a standardized measure to evaluate the GAD across its severity levels. The lack of objective and multi-level quantitative diagnostic criteria poses as a significant challenge for individualized treatment strategies. To address this need, this study aims to establish a GAD grading and quantification diagnostic model by integrating an electroencephalogram (EEG) and ensemble learning. In this context, a total of 39 normal subjects and 80 GAD patients were recruited and divided into four groups: normal control, mild GAD, moderate GAD, and severe GAD. Ten minutes resting state EEG data were collected for every subject. Functional connectivity features were extracted from each EEG segment with different time windows. Then, ensemble learning was employed for GAD classification studies and brain mechanism analysis. Hence, the results showed that the Catboost model with a 10 s time window achieved an impressive 98.1% accuracy for four-level classification. Particularly, it was found that those functional connections situated between the frontal and temporal lobes were significantly more abundant than in other regions, with the beta rhythm being the most prominent. The analysis framework and findings of this study provide substantial evidence for the applications of artificial intelligence in the clinical diagnosis of GAD.

18.
Food Chem ; 446: 138831, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38402759

RESUMEN

Carvacrol is well-known natural antimicrobial compounds. However, its usage in fruit preservation is restricted owing to poor water solubility. Our study aims to address this limitation by combining carvacrol with whey protein isolate (WPI) to form nanoemulsion and enhancing antimicrobial properties and stability of nanoemulsion through ε-polylysine addition, thereby improving their application in fruit preservation. The results indicated that the nanoemulsion exhibited a double-layer structure. The physicochemical properties and storage stability were found to be favorable under the conditions of WPI (0.3 wt% v/v), Carvacrol (0.5 % v/v), and ε-polylysine (0.3 wt% v/v). In addition, the nanoemulsion had inhibitory effects on Staphylococcus aureus, Escherichia coli, and Aspergillus niger at concentrations of minimal inhibition concentration (32, 32, and 200 µg/mL, respectively). In addition, during a 7-day storage period, the nanoemulsion effectively preserved mangoes. Therefore, nanoemulsion could serve as a candidate for control of postharvest mangoes spoilage and extend its period of storage.


Asunto(s)
Antiinfecciosos , Cimenos , Mangifera , Polilisina/química , Emulsiones/farmacología , Antiinfecciosos/farmacología , Escherichia coli
19.
Zookeys ; 1203: 239-251, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855790

RESUMEN

Taenioides sp. is a small temperate fish originally known to inhabit muddy bottoms of brackish waters in coastal areas of China. However, it began to invade multiple inland freshwaters and caused severe damage to Chinese aquatic ecosystems in recent years. To investigate the sources and invasive history of this species, we examined the population structure of 141 individuals collected from seven locations based on partial mitochondrial D-loop regions. The results revealed that the genetic diversity gradually decreased from south to north, with the Yangtze River Estuary and Taihu Lake populations possessing the highest haplotype diversity (Hd), average number of differences (k), and nucleotide diversity (π) values, suggesting that they may be the sources of Taenioides sp. invasions. Isolation-by-distance analysis revealed a non-significant correlation (p = 0.166) between genetic and geographic distances among seven populations, indicating that dispersal mediated through the regional hydraulic projects may have played an essential role in Taenioides sp. invasions. The population genetic structure analysis revealed two diverged clades among seven populations, with clade 2 only detected in source populations, suggesting a possible difference in the invasion ability of the two clades. Our results provide insights into how native estuary fish become invasive through hydraulic projects and may provide critical information for the future control of this invasive species.

20.
Macromol Biosci ; 24(5): e2300476, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38245857

RESUMEN

Peripheral nerve injuries (PNI) represent a prevalent and severe category of damage resulting from traumatic incidents. Predominantly, the deficiency in nerve regeneration can be ascribed to enduring inflammatory reactions, hence imposing substantial clinical implications for patients. Fisetin, a flavonoid derived from plants, is naturally present in an array of vegetables and fruits, including strawberries, apples, onions, and cucumbers. It exhibits immunomodulatory properties through the reduction of inflammation and oxidative stress. In the present research, a nerve defect is addressed for the first time utilizing a scaffold primed for controlled fisetin release. In this regard, fisetin-loaded chitosan hydrogels are incorporated into the lumen of polycaprolactone (PCL) nerve guide conduits (NGCs). The hydrogel maintained a steady release of an appropriate fisetin dosage. The study outcomes indicated that the fisetin/chitosan/polycaprolactone (FIS/CS/PCL) NGCs amplified Schwann cell proliferation and neural expression, curtailed oxidative stress, alleviated inflammation, and improved functions, electrophysiological properties, and morphology. This pioneering scaffold has the potential to contribute significantly to the field of neuroengineering.


Asunto(s)
Quitosano , Flavonoles , Hidrogeles , Inflamación , Regeneración Nerviosa , Estrés Oxidativo , Poliésteres , Flavonoles/farmacología , Quitosano/química , Quitosano/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Regeneración Nerviosa/efectos de los fármacos , Poliésteres/química , Poliésteres/farmacología , Inflamación/tratamiento farmacológico , Inflamación/patología , Células de Schwann/efectos de los fármacos , Células de Schwann/metabolismo , Andamios del Tejido/química , Ratas , Regeneración Tisular Dirigida/métodos , Proliferación Celular/efectos de los fármacos , Flavonoides/farmacología , Flavonoides/química , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Traumatismos de los Nervios Periféricos/patología , Traumatismos de los Nervios Periféricos/terapia
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