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1.
Sci Rep ; 14(1): 11026, 2024 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744903

RESUMEN

Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02-1.09), vascular dementia (HR, 1.08; 95% CI 1.01-1.15), and non-Alzheimer's disease non-vascular dementia (HR, 1.09; 95% CI 1.03-1.14). No significant association was observed for Alzheimer's disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia.


Asunto(s)
Bancos de Muestras Biológicas , Demencia , Composición Familiar , Humanos , Femenino , Masculino , Reino Unido/epidemiología , Demencia/epidemiología , Demencia/etiología , Persona de Mediana Edad , Anciano , Factores de Riesgo , Estudios Prospectivos , Incidencia , Modelos de Riesgos Proporcionales , Encéfalo/patología , Biobanco del Reino Unido
2.
Genomics ; 116(3): 110855, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38703968

RESUMEN

Clostridium butyricum is a Gram-positive anaerobic bacterium known for its ability to produce butyate. In this study, we conducted whole-genome sequencing and assembly of 14C. butyricum industrial strains collected from various parts of China. We performed a pan-genome comparative analysis of the 14 assembled strains and 139 strains downloaded from NCBI. We found that the genes related to critical industrial production pathways were primarily present in the core and soft-core gene categories. The phylogenetic analysis revealed that strains from the same clade of the phylogenetic tree possessed similar antibiotic resistance and virulence factors, with most of these genes present in the shell and cloud gene categories. Finally, we predicted the genes producing bacteriocins and botulinum toxins as well as CRISPR systems responsible for host defense. In conclusion, our research provides a desirable pan-genome database for the industrial production, food application, and genetic research of C. butyricum.

3.
Small ; : e2311861, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38708808

RESUMEN

Low-range light absorption and rapid recombination of photo-generated charge carriers have prevented the occurrence of effective and applicable photocatalysis for decades. Quantum dots (QDs) offer a solution due to their size-controlled photon properties and charge separation capabilities. Herein, well-dispersed interstitial nitrogen-doped TiO2 QDs with stable oxygen vacancies (N-TiO2-x-VO) are fabricated by using a low-temperature, annealing-assisted hydrothermal method. Remarkably, electrostatic repulsion prevented aggregation arising from negative charges accumulated in situ on the surface of N-TiO2-x-VO, enabling complete solar spectrum utilization (200-800 nm) with a 2.5 eV bandgap. Enhanced UV-vis photocatalytic H2 evolution rate (HER) reached 2757 µmol g-1 h-1, 41.6 times higher than commercial TiO2 (66 µmol g-1 h-1). Strikingly, under visible light, HER rate was 189 µmol g-1 h-1. Experimental and simulated studies of mechanisms reveal that VO can serve as an electron reservoir of photo-generated charge carriers on N-doped active sites, and consequently, enhance the separation rate of exciton pairs. Moreover, the negative free energy (-0.35 V) indicates more favorable thermodynamics for HER as compared with bulk TiO2 (0.66 V). This research work paves a new way of developing efficient photocatalytic strategies of HER that are applicable in the sustainable carbon-zero energy supply.

4.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732136

RESUMEN

In the context of sustainable agriculture and biomaterial development, understanding and enhancing plant secondary cell wall formation are crucial for improving crop fiber quality and biomass conversion efficiency. This is especially critical for economically important crops like upland cotton (Gossypium hirsutum L.), for which fiber quality and its processing properties are essential. Through comprehensive genome-wide screening and analysis of expression patterns, we identified a particularly high expression of an R2R3 MYB transcription factor, GhMYB52 Like, in the development of the secondary cell wall in cotton fiber cells. Utilizing gene-editing technology to generate a loss-of-function mutant to clarify the role of GhMYB52 Like, we revealed that GhMYB52 Like does not directly contribute to cellulose synthesis in cotton fibers but instead represses a subset of lignin biosynthesis genes, establishing it as a lignin biosynthesis inhibitor. Concurrently, a substantial decrease in the lint index, a critical measure of cotton yield, was noted in parallel with an elevation in lignin levels. This study not only deepens our understanding of the molecular mechanisms underlying cotton fiber development but also offers new perspectives for the molecular improvement of other economically important crops and the enhancement of biomass energy utilization.


Asunto(s)
Fibra de Algodón , Regulación de la Expresión Génica de las Plantas , Gossypium , Lignina , Proteínas de Plantas , Lignina/biosíntesis , Gossypium/genética , Gossypium/metabolismo , Gossypium/crecimiento & desarrollo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Pared Celular/metabolismo , Pared Celular/genética , Celulosa/biosíntesis , Celulosa/metabolismo , Vías Biosintéticas
5.
Sci Total Environ ; 930: 172847, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38685422

RESUMEN

Earth's Critical Zone exhibits remarkable heterogeneity and complexity. Hence, further investigation is required to examine the composition of Earth's Critical Zone as well as the diverse eco-hydrological patterns they exhibit under varying climatic and geological circumstances. This exploration should primarily be conducted through the investigation and experiments of the hillslope unit, where the topography and weathered bedrock are representative, with particular emphasis on semi-arid regions where water resources serve as the primary limiting factor. Here, we have determined that the structure of the weathering profile displays systematic variation across the topography and heterogeneous landscape on uninterrupted slopes. Differences in the structure of the subsurface critical zone led to differences in its water storage capacity at the same time. Runoff in alpine shrubs and forests was dominated by subsurface runoff, and grassland was dominated by surface runoff. In the alpine shrub immediately adjacent to the watershed, an estimated quantity of 129 mm of water is stored within the unsaturated zone of the soil, serving as exchange water to replenish moisture in the underlying bedrock. In contrast to alpine shrubs, an estimated quantity of 62.7 mm of water originates from the unsaturated zone of soil and weathered bedrock in the forest. However, approximately 21.1 mm of moisture is unavailable to plants. The soil water storage in grasslands exhibits a decline throughout the growing season, with a subsequent augmentation occurring solely after substantial precipitation events exceeding 20 mm. In wet years, dynamic storage predominantly manifests as groundwater saturation throughout the entire ground and high subsurface runoff. In dry years, the limited runoff response indicates that the catchment's dynamic water storage primarily comprises "indirect" water storage, which predominantly resides within the soil, saprolite, and weathered rock below the "field capacity", subsequently being released into the atmosphere through evapotranspiration.

6.
J Virol ; 98(5): e0195923, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38634598

RESUMEN

The role of Culex mosquitoes in the transmission of Japanese encephalitis virus (JEV) is crucial, yet the mechanisms of JEV infection in these vectors remain unclear. Previous research has indicated that various host factors participate in JEV infection. Herein, we present evidence that mosquito sialic acids enhance JEV infection both in vivo and in vitro. By treating mosquitoes and C6/36 cells with neuraminidase or lectin, the function of sialic acids is effectively blocked, resulting in significant inhibition of JEV infection. Furthermore, knockdown of the sialic acid biosynthesis genes in Culex mosquitoes also leads to a reduction in JEV infection. Moreover, our research revealed that sialic acids play a role in the attachment of JEV to mosquito cells, but not in its internalization. To further explore the mechanisms underlying the promotion of JEV attachment by sialic acids, we conducted immunoprecipitation experiments to confirm the direct binding of sialic acids to the last α-helix in JEV envelope protein domain III. Overall, our study contributes to a molecular comprehension of the interaction between mosquitoes and JEV and offers potential strategies for preventing the dissemination of flavivirus in natural environments.IMPORTANCEIn this study, we aimed to investigate the impact of glycoconjugate sialic acids on mosquito infection with Japanese encephalitis virus (JEV). Our findings demonstrate that sialic acids play a crucial role in enhancing JEV infection by facilitating the attachment of the virus to the cell membrane. Furthermore, our investigation revealed that sialic acids directly bind to the final α-helix in the JEV envelope protein domain III, thereby accelerating virus adsorption. Collectively, our results highlight the significance of mosquito sialic acids in JEV infection within vectors, contributing to a better understanding of the interaction between mosquitoes and JEV.


Asunto(s)
Culex , Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Mosquitos Vectores , Ácidos Siálicos , Acoplamiento Viral , Virus de la Encefalitis Japonesa (Especie)/fisiología , Virus de la Encefalitis Japonesa (Especie)/metabolismo , Animales , Culex/virología , Culex/metabolismo , Encefalitis Japonesa/virología , Encefalitis Japonesa/metabolismo , Mosquitos Vectores/virología , Ácidos Siálicos/metabolismo , Línea Celular , Proteínas del Envoltorio Viral/metabolismo , Proteínas del Envoltorio Viral/genética , Internalización del Virus , Ratones , Neuraminidasa/metabolismo , Neuraminidasa/genética
7.
Res Sq ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38645017

RESUMEN

Using spatial mapping processes to learn about threat and safety in an environment is crucial for survival. Research using conditioning paradigms has explored the effects of state (transient arousal) and trait anxiety (anxiety as an aspect of personality) on threat learning and acquisition. However, results are mixed, and little is known regarding why some individuals do not learn to discriminate between threat and safety during contextual conditioning. We used a virtual reality (VR) contextual threat conditioning paradigm to elucidate the effects of state and trait anxiety on contextual threat learning. 70 healthy participants (46 female) navigated and "picked" flowers in a VR environment. Flowers picked in the dangerous zone (half of the environment) were paired with an electric shock (or "bee sting") to the hand; flowers picked in the safe zone were never paired with a shock. Participants also collected and returned neutral objects as a measure of spatial memory. Galvanic skin response (GSR) was measured throughout the task and anxiety was assessed via the State Trait Anxiety Inventory (STAI). Participants were categorized as learners if they correctly identified the two zones after the task. Non-learners, compared to learners, performed significantly worse during the spatial memory task and demonstrated significantly higher state anxiety scores and GSR levels throughout the task. Learners showed higher skin conductance response (SCR) in the dangerous zone compared to the safe zone while non-learners showed no SCR differences between zones. These results indicate that state anxiety may impair spatial mapping, disrupting contextual threat learning.

8.
J Environ Sci (China) ; 143: 35-46, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38644022

RESUMEN

Selenium (Se) in paddy rice is one of the significant sources of human Se nutrition. However, the effect of arsenic (As) pollution in soil on the translocation of Se species in rice plants is unclear. In this research, a pot experiment was designed to examine the effect of the addition of 50 mg As/kg soil as arsenite or arsenate on the migration of Se species from soil to indica Minghui 63 and Luyoumingzhan. The results showed that the antagonism between inorganic As and Se was closely related to the rice cultivar and Se oxidation state in soil. Relative to the standalone selenate treatment, arsenite significantly (p < 0.05) decreased the accumulation of selenocystine, selenomethionine and selenate in the roots, stems, sheaths, leaves, brans and kernels of both cultivars by 21.4%-100.0%, 40.0%-100.0%, 41.0%-100%, 5.4%-96.3%, 11.3%-100.0% and 26.2%-39.7% respectively, except for selenocystine in the kernels of indica Minghui 63 and selenomethionine in the leaves of indica Minghui 63 and the stems of indica Luyoumingzhan. Arsenate also decreased (p < 0.05) the accumulation of selenocystine, selenomethionine and selenate in the roots, stems, brans and kernels of both cultivars by 34.9%-100.0%, 30.2%-100.0%, 11.3%-100.0% and 5.6%-39.6% respectively, except for selenate in the stems of indica Minghui 63. However, relative to the standalone selenite treatment, arsenite and arsenate decreased (p < 0.05) the accumulation of selenocystine, selenomethionine and selenite only in the roots of indica Minghui 63 by 45.5%-100.0%. Our results suggested that arsenite and arsenate had better antagonism toward Se species in selenate-added soil than that in selenite-added soil; moreover, arsenite had a higher inhibiting effect on the accumulation of Se species than arsenate.


Asunto(s)
Arsénico , Oryza , Selenio , Contaminantes del Suelo , Suelo , Oryza/metabolismo , Contaminantes del Suelo/análisis , Contaminantes del Suelo/metabolismo , Selenio/análisis , Selenio/metabolismo , Arsénico/análisis , Arsénico/metabolismo , Suelo/química , Arsenitos
9.
Artículo en Inglés | MEDLINE | ID: mdl-38574238

RESUMEN

Acute lung injury is a common respiratory disease characterized by diffuse alveolar injury and interstitial edema, as well as a hyperinflammatory response, lung cell damage and oxidative stress. Foxq1, a member of the FOX family of transcription factors, is expressed in various tissues, such as the lungs, liver, and kidneys, and contributes to various biological processes, such as stress, metabolism, cell cycle arrest, and aging-related apoptosis. However, the role of Foxq1 in acute lung injury is unknown. We constructed ex vivo and in vivo acute lung injury models by lipopolysaccharide tracheal perfusion of ICR mice and conditioned medium stimulation of injured MLE-12 cells. Foxq1 expression was increased, and its localization was altered in our acute lung injury model. In normal or injured MLE-12 cells, knockdown of Foxq1 promoted cell survival, and overexpression had the opposite effect. This regulatory effect was likely mediated by Tle1 and the NFκB/Bcl2/Bax signaling pathway. These data suggest a potential link between Foxq1 and acute lung injury, indicating that Foxq1 can be used as a biomarker for the diagnosis of acute lung injury. Targeted inhibition of Foxq1 expression could promote alveolar epithelial cell survival and may provide a strategy for mitigating acute lung injury.

10.
Artículo en Inglés | MEDLINE | ID: mdl-38683709

RESUMEN

Multiview attribute graph clustering aims to cluster nodes into disjoint categories by taking advantage of the multiview topological structures and the node attribute values. However, the existing works fail to explicitly discover the inherent relationships in multiview topological graph matrices while considering different properties between the graphs. Besides, they cannot well handle the sparse structure of some graphs in the learning procedure of graph embeddings. Therefore, in this article, we propose a novel contrastive multiview attribute graph clustering (CMAGC) with adaptive encoders method. Within this framework, the adaptive encoders concerning different properties of distinct topological graphs are chosen to integrate multiview attribute graph information by checking whether there exists high-order neighbor information or not. Meanwhile, the number of layers of the GCN encoders is selected according to the prior knowledge related to the characteristics of different topological graphs. In particular, the feature-level and cluster-level contrastive learning are conducted on the multiview soft assignment representations, where the union of the first-order neighbors from the corresponding graph pairs is regarded as the positive pairs for data augmentation and the sparse neighbor information problem in some graphs can be well dealt with. To the best of our knowledge, it is the first time to explicitly deal with the inherent relationships from the interview and intraview perspectives. Extensive experiments are conducted on several datasets to verify the superiority of the proposed CMAGC method compared with the state-of-the-art methods.

11.
BMC Cancer ; 24(1): 510, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654281

RESUMEN

BACKGROUND: To develop a deep learning(DL) model utilizing ultrasound images, and evaluate its efficacy in distinguishing between benign and malignant parotid tumors (PTs), as well as its practicality in assisting clinicians with accurate diagnosis. METHODS: A total of 2211 ultrasound images of 980 pathologically confirmed PTs (Training set: n = 721; Validation set: n = 82; Internal-test set: n = 89; External-test set: n = 88) from 907 patients were retrospectively included in this study. The optimal model was selected and the diagnostic performance evaluation is conducted by utilizing the area under curve (AUC) of the receiver-operating characteristic(ROC) based on five different DL networks constructed at varying depths. Furthermore, a comparison of different seniority radiologists was made in the presence of the optimal auxiliary diagnosis model. Additionally, the diagnostic confusion matrix of the optimal model was calculated, and an analysis and summary of misjudged cases' characteristics were conducted. RESULTS: The Resnet18 demonstrated superior diagnostic performance, with an AUC value of 0.947, accuracy of 88.5%, sensitivity of 78.2%, and specificity of 92.7% in internal-test set, and with an AUC value of 0.925, accuracy of 89.8%, sensitivity of 83.3%, and specificity of 90.6% in external-test set. The PTs were subjectively assessed twice by six radiologists, both with and without the assisted of the model. With the assisted of the model, both junior and senior radiologists demonstrated enhanced diagnostic performance. In the internal-test set, there was an increase in AUC values by 0.062 and 0.082 for junior radiologists respectively, while senior radiologists experienced an improvement of 0.066 and 0.106 in their respective AUC values. CONCLUSIONS: The DL model based on ultrasound images demonstrates exceptional capability in distinguishing between benign and malignant PTs, thereby assisting radiologists of varying expertise levels to achieve heightened diagnostic performance, and serve as a noninvasive imaging adjunct diagnostic method for clinical purposes.


Asunto(s)
Aprendizaje Profundo , Neoplasias de la Parótida , Ultrasonografía , Humanos , Estudios Retrospectivos , Ultrasonografía/métodos , Neoplasias de la Parótida/diagnóstico por imagen , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/diagnóstico , Masculino , Persona de Mediana Edad , Femenino , Adulto , Anciano , Adulto Joven , Curva ROC , Diagnóstico Diferencial , Adolescente , Anciano de 80 o más Años , Sensibilidad y Especificidad , Niño
12.
J Neurosci ; 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658167

RESUMEN

Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects millions of seniors in the US. Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to study neurophysiology in AD and its prodromal condition, mild cognitive impairment (MCI). The intrinsic neural timescale (INT), which can be estimated through the magnitude of the autocorrelation of neural signals from rs-fMRI, is thought to quantify the duration that neural information is stored in a local circuit. Such heterogeneity of the timescales forms a basis of the brain functional hierarchy and captures an aspect of circuit dynamics relevant to excitation/inhibition balance, which is broadly relevant for cognitive functions. Given that, we applied rs-fMRI to test whether distinct changes of INT at different hierarchies are present in people with MCI, those progressing to AD (called Converter), and AD patients of both sexes. Linear mixed effect model was implemented to detect altered hierarchical gradients across populations followed by pairwise comparisons to identify regional differences. High similarities between AD and Converter were observed. Specifically, the inferior temporal, caudate, pallidum areas exhibit significant alterations in both AD and Converter. Distinct INT related pathological changes in MCI and AD were found. For AD/Converter, neural information is stored for a longer time in lower hierarchical areas, while higher levels of hierarchy seem to be preferentially impaired in MCI leading to a less pronounced hierarchical gradients. These results inform that the INT holds great potential as an additional measure for AD prediction, even a stable biomarker for clinical diagnosis.Significance Statement We observed high similarities of intrinsic neural timescales (INT) between patients with Alzheimer's Disease (AD) and people that will later progress to AD (called Converter), deviating from cognitively normal individuals. This indicates that pathological excitation/inhibition imbalance already started before the conversion to AD. We also revealed distinct pathophysiological changes in stable mild cognitive impairment (MCI) and AD/Converter. For the AD and Converter, neural information is stored for a longer time in lower brain hierarchical areas; while higher levels of the hierarchy seem to be preferentially impaired in stable MCI. These results suggest the potential for INT as an additional measure for AD prediction, even a stable biomarker for clinical diagnosis.

13.
J Biophotonics ; 17(5): e202400023, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38576140

RESUMEN

Light exposure has been proven to have a significant impact on human health. As a result, researchers are increasingly exploring its potential benefits and drawbacks. With advancements in understanding light and the manufacturing of light sources, modern health lighting has become widely utilized in daily life and plays a critical role in the prevention and treatment of various illnesses. The use of light in healthcare is a global trend, with many countries actively promoting the development and application of relevant scientific research and medical technology. This field has gained worldwide attention and support from scientists and doctors alike. In this review, we examine the application of lighting in human health and recent breakthroughs in light exposure related to pathology, therapeutic strategies, molecular changes, and more. Finally, we also discuss potential future developments and areas of application.


Asunto(s)
Luz , Humanos , Salud , Fototerapia , Iluminación
14.
Biomed Pharmacother ; 174: 116476, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38520872

RESUMEN

BACKGROUND: Increasing global overweight and obesity rates not only increase the prevalence of myocardial infarction (MI), but also exacerbate ischemic injury and result in worsened prognosis. Currently, there are no drugs that can reverse myocardial damage once MI has occurred, therefore discovering drugs that can potentially limit the extent of ischemic damage to the myocardium is critical. Resveratrol is a polyphenol known for its antioxidant properties, however whether prolonged daily intake of resveratrol during obesity can protect against MI-induced damage remains unexplored. METHODS: We established murine models of obesity via high-fat/high-fructose diet, along with daily administrations of resveratrol or vehicle, then performed surgical MI to examine the effects and mechanisms of resveratrol in protecting against myocardial ischemic injury. RESULTS: Daily administration of resveratrol in obese mice robustly protected against myocardial ischemic injury and improved post-MI cardiac function. Resveratrol strongly inhibited oxidative and DNA damage via activating SIRT3/FOXO3a-dependent antioxidant enzymes following MI, which were completely prevented upon administration of 3-TYP, a selective SIRT3 inhibitor. Hence, the cardioprotective effects of prolonged resveratrol intake in protecting obese mice against myocardial ischemic injury was due to reestablishment of intracellular redox homeostasis through activation of SIRT3/FOXO3a signaling pathway. CONCLUSION: Our findings provide important new evidence that supports the daily intake of resveratrol, especially in those overweight or obese, which can robustly decrease the extent of ischemic damage following MI. Our study therefore provides new mechanistic insight and suggests the therapeutic potential of resveratrol as an invaluable drug in the treatment of ischemic heart diseases.


Asunto(s)
Proteína Forkhead Box O3 , Homeostasis , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad , Oxidación-Reducción , Resveratrol , Transducción de Señal , Sirtuina 3 , Animales , Resveratrol/farmacología , Transducción de Señal/efectos de los fármacos , Sirtuina 3/metabolismo , Masculino , Oxidación-Reducción/efectos de los fármacos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/complicaciones , Proteína Forkhead Box O3/metabolismo , Homeostasis/efectos de los fármacos , Ratones , Antioxidantes/farmacología , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Infarto del Miocardio/prevención & control , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/tratamiento farmacológico , Cardiotónicos/farmacología , Estilbenos/farmacología , Estilbenos/uso terapéutico
15.
J Med Chem ; 67(6): 4560-4582, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38502936

RESUMEN

Inspired by the structure of dysoxylactam A (DLA) that has been demonstrated to reverse P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) effectively, 61 structurally simplified cyclolipopeptides were thus designed and synthesized via an effective method, and their reversing P-gp-mediated MDR potentials were evaluated, which provided a series of more potent analogues and allowed us to explore their structure-activity relationship (SAR). Among them, a well-simplified compound, 56, with only two chiral centers that all derived from amino acids dramatically reversed drug resistance in KBV200 cells at 10 µM in combination with vinorelbine (VNR), paclitaxel (PTX), and adriamycin (ADR), respectively, which is more promising than DLA. The mechanism study showed that 56 reversed the MDR of tumor cells by inhibiting the transport function of P-gp rather than reducing its expression. Notably, compound 56 effectively restored the sensitivity of MDR tumors to VNR in vivo at a dosage without obvious toxicity.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Resistencia a Antineoplásicos , Lipopéptidos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Resistencia a Múltiples Medicamentos , Subfamilia B de Transportador de Casetes de Unión a ATP , Doxorrubicina/farmacología , Línea Celular Tumoral
16.
Sci Rep ; 14(1): 6162, 2024 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-38485743

RESUMEN

Marital status is an independent prognostic factor for survival in many types of cancers, but its prognostic impact on patients with prostate cancer (PCa) has not been established. The aim of this study was to explore the independent prognostic factors of PCa and to investigate the effect of marital status on survival outcomes in patients with different stratified by PCa. Using the surveillance, epidemiology, and end results (SEER) database, we collected data on 584,655 PCa patients diagnosed between 1975 and 2019. Marital status was classified as married, divorced, widowed, and single. We used the Kaplan-Meier analysis and single multivariate Cox proportional hazards regression analysis to determine the effect of marital status on overall survival (OS) and cancer-specific survival (CSS). In addition, we performed subgroup analyses for different ages, Gleason score and PSA values, and performed a 1:1 propensity score matching (PSM) to reduce the impact of confounding factors to obtain more accurate matching results. According to our findings, marital status was an independent prognostic factor for the survival of PCa patients and a better prognosis of married patients. Moreover, we also found that factors such as age, TNM stage, Gleason score, and PSA concentration were also considered as important predictors for the prognosis of PCa. The above findings can facilitate early detection and treatment of high-risk PCa patients, prolong their life and reduce family burden.


Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Puntaje de Propensión , Programa de VERF , Estado Civil , Pronóstico
17.
Ocul Immunol Inflamm ; : 1-7, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38427335

RESUMEN

PURPOSE: To report the effect of topical application of recombinant human nerve growth factor (rhNGF) eye drops on corneal epithelial regeneration in patients with refractory epitheliopathy. METHODS: A retrospective chart review was conducted on patients treated with topical rhNGF for refractory epithelial keratopathy due to stage I neurotrophic keratitis (NK). Data regarding demographics and ocular/systemic past medical history was extracted from patient charts. Visual acuity and corneal staining scores were recorded at baseline and subsequent follow-up visits at 8 weeks and 3 months. Measurements from the worse eye were used to compare before and after treatment values. RESULTS: We identified 14 patients (median age 68 years, 21% male) who received rhNGF treatment for refractory epithelial keratopathy. After an 8-week treatment with topical rhNGF, the median corneal staining score in the worse eye improved from 4 to 1 (p = 0.001). All patients showed at least one-grade improvement in corneal staining at 8 weeks, with sustained effect in seven patients at 3 months. A better response was observed in eyes with post-radiation epithelial keratopathy, LASIK, and Sjogren's disease. Those with chronic use of other topical treatments and uncontrolled diabetes mellitus demonstrated incomplete responses. Eight patients reported mild-to-moderate ocular discomfort from drop application that fully resolved after completion of treatment. CONCLUSIONS: Topical rhNGF was effective and safe for refractory epithelial keratopathy in our small cohort, but sustained effects were seen only in certain etiologies for up to 3 months. Further studies are needed for optimal dosing and duration based on underlying causes.

18.
Chin J Traumatol ; 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38458896

RESUMEN

PURPOSE: Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries. METHODS: This case control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median and quartiles. Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. RESULTS: According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% CI: 2.08 - 25.42, p = 0.002), 2.85 (95% CI: 1.11 - 7.31, p = 0.030), 2.62 (95% CI: 1.12 - 6.13, p = 0.027), 2.44 (95% CI: 1.25 - 4.76, p = 0.009), and 1.5 (95% CI: 1.10 - 2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ2 = 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ2 = 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. CONCLUSION: Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

19.
J Phys Chem Lett ; 15(8): 2111-2116, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38360578

RESUMEN

Depletion forces, commonly modeled with rigid body assumptions, inadequately describe nanoparticle behavior. This study introduces the roles of Soret and Dufour effects in nanoparticle systems, focusing on mass and energy gradient interchange. The Dufour effect drives energy flow through mass gradients, which implies the possibility of driving the energy flow near the nanoparticles to induce phase transitions via manipulating the monomer concentrations. Our experimental platform confirmed these theories, synthesizing HCP quantum dots from Au, Ag, Pd, and mixed halide perovskites under varied precursor concentrations. By analyzing energy flow and nucleation dynamics through the Dufour effect, we mapped phase transition thresholds, linking them to material entropy. This study provides insight into nanoparticle assembly and phase behavior, highlighting the significance of entropy in nucleation dynamics.

20.
J Org Chem ; 89(5): 3471-3480, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38350101

RESUMEN

A Pd-catalyzed thiocarbonylative cyclization of N-(o-iodoaryl)acrylamides with easily accessible thioformates has been developed. The reaction has a wide substrate scope with good yields and represents a powerful route to the synthesis of thioester-functionalized oxindoles. Both S-aryl and alkyl thioformates as the thioester sources were well tolerated. The active Pd-CO intermediate may play an important role in the transformation process.

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