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1.
J Affect Disord ; 358: 52-60, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38703907

RESUMEN

BACKGROUND: Adolescence involves a period of swift change, including the development of personality vulnerabilities (i.e., dependency and self-criticism) that act as transdiagnostic factors to psychopathology. Over the past several decades, numerous short revisions have condensed the Depressive Experiences Questionnaire (DEQ) into more efficient measures of personality vulnerability. Prior research has investigated the psychometric properties of the short DEQs in adult and clinical samples. However, there has been insufficient exploration within adolescents, who are in addition marked by fluctuating personality vulnerabilities. METHOD: A representative large sample of adolescents and emerging adults in China aged 10 to 25 (N = 23,953) was administered five short DEQs, including the Revised DEQ (RevDEQ), Reconstructed DEQ (RecDEQ), Theoretical DEQ-21/12 (TDEQ-21/12) and adolescent DEQ (DEQ-A). The data was evaluated for internal consistency and criterion-related validity, while factor structure and measurement invariances across gender and age groups were analyzed by confirmatory factor analysis (CFA). A subset of the original sample (N = 2874) was retested after six months and analyzed for test-retest reliability and cross-time invariance. RESULT: CFA of the TDEQ-21/12 and RecDEQ supported the intended two-factor model. Good criterion-related validity, internal consistency and test-retest reliability for these three versions were found. Satisfying measurement invariances across gender, time, and age groups were established. LIMITATION: The study's scope was confined to non-clinical adolescent populations within China, highlighting a gap in cross-cultural and clinical applicability. CONCLUSION: The present study supports the use of the TDEQ-21/12 and RecDEQ as valid and concise instruments for measuring Chinese adolescent personality vulnerability.

2.
Nat Commun ; 15(1): 3782, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38710678

RESUMEN

Thermoelectrics have great potential for use in waste heat recovery to improve energy utilization. Moreover, serving as a solid-state heat pump, they have found practical application in cooling electronic products. Nevertheless, the scarcity of commercial Bi2Te3 raw materials has impeded the sustainable and widespread application of thermoelectric technology. In this study, we developed a low-cost and earth-abundant PbS compound with impressive thermoelectric performance. The optimized n-type PbS material achieved a record-high room temperature ZT of 0.64 in this system. Additionally, the first thermoelectric cooling device based on n-type PbS was fabricated, which exhibits a remarkable cooling temperature difference of ~36.9 K at room temperature. Meanwhile, the power generation efficiency of a single-leg device employing our n-type PbS material reaches ~8%, showing significant potential in harvesting waste heat into valuable electrical power. This study demonstrates the feasibility of sustainable n-type PbS as a viable alternative to commercial Bi2Te3, thereby extending the application of thermoelectrics.

3.
Molecules ; 29(7)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38611758

RESUMEN

Alzheimer's disease (AD) is a complex degenerative disease of the central nervous system that is clinically characterized by a progressive decline in memory and cognitive function. The pathogenesis of AD is intricate and not yet fully understood. Neuroinflammation, particularly microglial activation-mediated neuroinflammation, is believed to play a crucial role in increasing the risk, triggering the onset, and hastening the progression of AD. Modulating microglial activation and regulating microglial energy metabolic disorder are seen as promising strategies to intervene in AD. The application of anti-inflammatory drugs and the targeting of microglia for the prevention and treatment of AD has emerged as a new area of research interest. This article provides a comprehensive review of the role of neuroinflammation of microglial regulation in the development of AD, exploring the connection between microglial energy metabolic disorder, neuroinflammation, and AD development. Additionally, the advancements in anti-inflammatory and microglia-regulating therapies for AD are discussed.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Microglía , Enfermedades Neuroinflamatorias , Sistema Nervioso Central , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico
4.
Int J Biol Macromol ; 269(Pt 2): 131720, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38677692

RESUMEN

The human nervous system is an incredibly intricate physiological network, and neural cells lack the ability to repair and regenerate after a brain injury. 3-dimensional (3D) bioprinting technology offers a promising strategy for constructing biomimetic organ constructs and in vitro brain/disease models. The bioink serves as a pivotal component that emulates the microenvironment of biomimetic construct and exerts a profound influence on cellular behaviors. In this study, a series of mechanically adjustable and dual crosslinking bioinks were developed using photocrosslinkable methacrylated silk fibroin (SilMA) in combination with the ionic crosslinking material, pectin, or pectin methacryloyl (PecMA) with silk fibroin (SF) supplementation. SilMA/pectin exhibited superior properties, with SilMA providing biocompatibility and adjustable mechanical properties, while the addition of pectin enhanced printability. The porous structure supported neural cell growth, and 15 % SilMA/0.5 % pectin bioinks displayed excellent printability and shape fidelity. Neural stem/progenitor cells (NSPCs)-loaded bioinks were used to construct a 3D brain model, demonstrating sustained vitality and high neuronal differentiation without the need for growth factors. The SilMA/pectin bioinks demonstrated adjustable mechanical properties, favorable biocompatibility, and an environment highly conducive to neural induction, offering an alternative approach for neural tissue engineering applications or in vitro brain models.

5.
Micromachines (Basel) ; 15(4)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38675253

RESUMEN

To obtain precise positional information, in this study, we propose an adaptive expectation-maximization (EM)-based Kalman filter (KF)/finite impulse response (FIR) integrated filter for inertial navigation system (INS)-based posture capture of human upper limbs. Initially, a data fusion model for wrist and elbow position is developed. Subsequently, the Mahalanobis distance is utilized to evaluate the performance of the filter. The integrated filter employs the EM-based KF to enhance noise estimation accuracy when the performance of KF declines. Conversely, upon deterioration in the performance of the EM-based KF, which is evaluated using the Mahalanobis distance, the FIR filter is employed to maintain the effectiveness of the data fusion filter. This research utilizes the proposed EM-based KF/FIR integrated filter to ascertain wrist and elbow positions. The empirical results demonstrate the proficiency of the proposed approach in estimating these positions, thereby overcoming the challenge and highlighting its inherent effectiveness.

6.
World J Gastroenterol ; 30(10): 1405-1419, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38596488

RESUMEN

BACKGROUND: Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology. Alkaline sphingomyelinase (alk-SMase) is specifically expressed by intestinal epithelial cells, and has been reported to play an anti-inflammatory role. However, the underlying mechanism is still unclear. AIM: To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium (DSS)-induced colitis. METHODS: Mice were administered 3% DSS drinking water, and disease activity index was determined to evaluate the status of colitis. Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran, and bacterial translocation was evaluated by measuring serum lipopolysaccharide. Intestinal epithelial cell ultrastructure was observed by electron microscopy. Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA, respectively. Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels. RESULTS: Compared to wild-type (WT) mice, inflammation and intestinal permeability in alk-SMase knockout (KO) mice were more severe beginning 4 d after DSS induction. The mRNA and protein levels of intestinal barrier proteins, including zonula occludens-1, occludin, claudin-3, claudin-5, claudin-8, mucin 2, and secretory immunoglobulin A, were significantly reduced on 4 d after DSS treatment. Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells. Furthermore, by day 4, mitochondria appeared swollen and degenerated. Additionally, compared to WT mice, serum malondialdehyde levels in KO mice were higher, and the antioxidant capacity was significantly lower. The expression of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment. mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased. Finally, colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone, which is an Nrf2 activator. CONCLUSION: Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.


Asunto(s)
Colitis Ulcerosa , Colitis , Enfermedad de Niemann-Pick Tipo A , Animales , Ratones , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Colitis/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Colon , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Mucosa Intestinal , Ratones Endogámicos C57BL , Ratones Noqueados , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedad de Niemann-Pick Tipo A/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , ARN Mensajero/metabolismo
7.
Sci Bull (Beijing) ; 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38688741

RESUMEN

Thermoelectric materials have a wide range of application because they can be directly used in refrigeration and power generation. And the Bi2Te3 stand out because of its excellent thermoelectric performance and are used in commercial thermoelectric devices. However, n-type Bi2Te3 has seriously hindered the development of Bi2Te3-based thermoelectric devices due to its weak mechanical properties and inferior thermoelectric performance. Therefore, it is urgent to develop a high-performance n-type Bi2Te3 polycrystalline. In this work, we employed interstitial Cu and the hot deformation process to optimize the thermoelectric properties of Bi2Te2.7Se0.3, and a high-performance thermoelectric module was fabricated based on this material. Our combined theoretical and experimental effort indicates that the interstitial Cu reduce the defect density in the matrix and suppresses the donor-like effect, leading to a lattice plainification effect in the material. In addition, the two-step hot deformation process significantly improves the preferred orientation of the material and boosts the mobility. As a result, a maximum ZT of 1.27 at 373 K and a remarkable high ZTave of 1.22 across the temperature range of 300-425 K are obtained. The thermoelectric generator (TEG, 7-pair) and thermoelectric cooling (TEC, 127-pair) modules were fabricated with our n-type textured Cu0.01Bi2Te2.7Se0.3 coupled with commercial p-type Bi2Te3. The TEC module demonstrates superior cooling efficiency compared with the commercial Bi2Te3 device, achieving a ΔT of 65 and 83.4 K when the hot end temperature at 300 and 350 K, respectively. In addition, the TEG module attains an impressive conversion efficiency of 6.5% at a ΔT of 225 K, which is almost the highest value among the reported Bi2Te3-based TEG modules.

8.
J Alzheimers Dis ; 98(2): 643-657, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38427489

RESUMEN

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease needing effective therapeutics urgently. Sildenafil, one of the approved phosphodiesterase-5 inhibitors, has been implicated as having potential effect in AD. Objective: To investigate the potential therapeutic benefit of sildenafil on AD. Methods: We performed real-world patient data analysis using the MarketScan® Medicare Supplemental and the Clinformatics® databases. We conducted propensity score-stratified analyses after adjusting confounding factors (i.e., sex, age, race, and comorbidities). We used both familial and sporadic AD patient induced pluripotent stem cells (iPSC) derived neurons to evaluate the sildenafil's mechanism-of-action. Results: We showed that sildenafil usage is associated with reduced likelihood of AD across four new drug compactor cohorts, including bumetanide, furosemide, spironolactone, and nifedipine. For instance, sildenafil usage is associated with a 54% reduced incidence of AD in MarketScan® (hazard ratio [HR] = 0.46, 95% CI 0.32- 0.66) and a 30% reduced prevalence of AD in Clinformatics® (HR = 0.70, 95% CI 0.49- 1.00) compared to spironolactone. We found that sildenafil treatment reduced tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic AD patient iPSC-derived neurons. RNA-sequencing data analysis of sildenafil-treated AD patient iPSC-derived neurons reveals that sildenafil specifically target AD related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in AD. Conclusions: These real-world patient data validation and mechanistic observations from patient iPSC-derived neurons further suggested that sildenafil is a potential repurposable drug for AD. Yet, randomized clinical trials are warranted to validate the causal treatment effects of sildenafil in AD.


Asunto(s)
Enfermedad de Alzheimer , Células Madre Pluripotentes Inducidas , Enfermedades Neurodegenerativas , Anciano , Estados Unidos , Humanos , Enfermedad de Alzheimer/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Citrato de Sildenafil/farmacología , Citrato de Sildenafil/uso terapéutico , Enfermedades Neurodegenerativas/metabolismo , Espironolactona/metabolismo , Espironolactona/farmacología , Proteínas tau/metabolismo , Medicare , Neuronas/metabolismo
9.
Int J Biol Macromol ; 266(Pt 1): 131140, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38537864

RESUMEN

Conventional textile dyeing relies on the use of dyes and pigments, which can cause severe environmental contamination and waste a large amount of water. Structural coloring is one of the effective ways to achieve environmentally friendly coloring of textiles. In this work, three plant polyphenols with the same o-benzenetriol structure (tannic acid (TA), gallic acid (GA), and tea polyphenol (TP)) were selected as raw materials. Three plant polyphenols can quickly form nanofilms at the gas-liquid interface through a Schiff base reaction with polyethyleneimine (PEI) under mildly alkaline conditions, which were deposited to the surface of silk fabric, allowing precise control over the thickness of film by adjusting the time, resulting in various structurally colored silk fabric. This method for creating structural colors is not substrate-specific and enables the quick production of structural colors on various textile substrates. Furthermore, the structural color silk fabric based on plant polyphenol has antibacterial performance. This textile coloring method is simple, cost-effective and environmentally friendly, providing a new approach to eco-friendly textile dyeing.


Asunto(s)
Color , Polifenoles , Seda , Textiles , Polifenoles/química , Seda/química , Colorantes/química , Antibacterianos/química , Antibacterianos/farmacología
11.
Artículo en Inglés | MEDLINE | ID: mdl-38310573

RESUMEN

BACKGROUND: To a certain extent, traditional Chinese medicine (TCM)-based anesthesia has replaced opiate administration in recent years. Preliminary drug screening has revealed that scopolamine may affect breast cancer (BC) metastasis by an unknown mechanism. METHODS: Network pharmacology, bioinformatics, and protein-protein interaction (PPI) topological analysis were implemented to identify the core genes linking scopolamine and BC. The core genes were then subjected to gene expression profiling interactive analysis (GEPIA). The top ten pathways were detected by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The impact of immune infiltration on the core gene difference and survival analyses was then determined. Molecular docking was then performed on the core genes and the main active components. RESULTS: Protein kinase 1 (AKT1), epidermal growth factor receptor (EGFR), heat shock protein 90 alpha class A (HSP90AA1), caspase 3 (CASP3), and estrogen receptor 1 (ESR1) were the key genes in the interaction between scopolamine and BC cells. The KEGG enrichment analysis disclosed that the top ten pathways significantly associated with the scopolamine response in BC included "protein glycosylation," "phosphoinositide 3-kinase (PI3K)-Akt signaling," "mitogen- activated protein kinase (MAPK) signaling" and others. The AKT1, EGFR, and especially the HSP90AA1 expression levels were correlated with survival in patients with BC. Immune infiltration also influenced the survival outcome. Molecular docking demonstrated that scopolamine bound and formed stable complexes with the protein products of all five aforementioned genes. CONCLUSION: Scopolamine has multiple targets regulating BC cell function and may increase the risk of metastasis during treatment. Therefore, it should be preoperatively administered with caution to patients with BC.

12.
Biomimetics (Basel) ; 9(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38248589

RESUMEN

Traditional textile dyeing uses chemical pigments and dyes, which consumes a large amount of water and causes serious environmental pollution. Structural color is an essential means of achieving green dyeing of textiles, and thin-film interference is one of the principles of structural coloring. In the assembly of structural color films, it is necessary to introduce dark materials to suppress light scattering and improve the brightness of the fabric. In this study, the conditions for the generation of nanofilms of catechin (CC) at the gas-liquid interface were successfully investigated. At the same time, environmentally friendly colored silk fabrics were novelly prepared using polycatechin (PCC) structural color films. In addition, it was found that various structural colors were obtained on the surface of silk fabrics by adjusting the time. Meanwhile, the color fastness of the structural colored fabrics was improved by introducing polyvinylpyrrolidone (PVP) to form a strong hydrogen bond between the fabric and catechin. PCC film is uniform and smooth, with a special double-layer structure, and can be attached to the surface of silk fabrics, giving the fabrics special structural colors. Through the thin-film interference formed between the visible light and the PCC film, the silk fabrics obtain bright, controllable, and uniform structural colors. This method is easy to operate and provides a new way of thinking for environmental-protection-oriented coloring of fabrics.

13.
Diabetol Metab Syndr ; 16(1): 17, 2024 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-38217060

RESUMEN

AIMS: To identify the gestational weight gain (GWG) patterns in women with gestational diabetes mellitus (GDM) and evaluate their association with offspring weight status from birth to 40 months. MATERIALS AND METHODS: This study included 2,723 GDM-mother-child pairs from the Beijing Birth Cohort Study. The association between GWG trajectories identified by the latent class model and offspring weight outcomes from birth to 40 months were evaluated, after adjustment for maternal age, parity, pre-pregnancy body mass index, maternal height, and blood glucose levels. RESULTS: Three GWG rate groups, including the non-excessive GWG group (1,994/2,732), excessive GWG group (598 /2,732), and excessive early GWG group (140/2,732), were identified in women with GDM, respectively. Compared to the non-excessive GWG group, the adjusted OR (aOR) and 95% CI were 1.83 (1.35-2.47) and 1.79 (1.06-3.01) for macrosomia, 1.33 (1.07-1.66) and 1.48 (1.01-2.17) for large for gestational age (LGA) in the excessive GWG group and excessive early GWG group. Excessive GWG was also associated with an increased risk of BMI-for-age at 40 months (aOR = 1.66, 95% CI 1.14-2.42). CONCLUSIONS: Both excessive GWG and excessive early GWG increased the risk of macrosomia and LGA in women with GDM, but only the excessive GWG was associated with childhood overweight/obesity. The results suggest the long-term impact of GWG on offspring weight status in women with GDM and the potential benefits of GWG restriction after GDM diagnosis.

14.
Mater Horiz ; 11(4): 876-902, 2024 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-38175543

RESUMEN

An MXene is a novel two-dimensional transition metal carbide or nitride, with a typical formula of Mn+1XnTx (M = transition metals, X = carbon or nitrogen, and T = functional groups). MXenes have found wide application in biomedicine and biosensing, owing to their high biocompatibility, abundant reactive surface groups, good conductivity, and photothermal properties. Applications include photo- and electrochemical sensors, energy storage, and electronics. This review will highlight recent applications of MXene and MXene-derived materials in drug delivery, tissue engineering, antimicrobial activity, and biosensors (optical and electrochemical). We further elaborate on recent developments in utilizing MXenes for photothermal cancer therapy, and we explore multimodal treatments, including the integration of chemotherapeutic agents or magnetic nanoparticles for enhanced therapeutic efficacy. The high surface area and reactivity of MXenes provide an interface to respond to the changes in the environment, allowing MXene-based drug carriers to respond to changes in pH, reactive oxygen species (ROS), and electrical signals for controlled release applications. Furthermore, the conductivity of MXene enables it to provide electrical stimulation for cultured cells and endows it with photocatalytic capabilities that can be used in antibiotic applications. Wearable and in situ sensors incorporating MXenes are also included. Major challenges and future development directions of MXenes in biomedical applications are also discussed. The remarkable properties of MXenes will undoubtedly lead to their increasing use in the applications discussed here, as well as many others.


Asunto(s)
Antibacterianos , Carbono , Nitritos , Elementos de Transición , Terapia Combinada , Portadores de Fármacos
15.
Bioengineering (Basel) ; 11(1)2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38247971

RESUMEN

The surge in deep learning-driven EMR research has centered on harnessing diverse data forms. Yet, the amalgamation of diverse modalities within time series data remains an underexplored realm. This study probes a multimodal fusion approach, merging temporal and non-temporal clinical notes along with tabular data. We leveraged data from 1271 myocardial infarction and 6450 stroke inpatients at a Beijing tertiary hospital. Our dataset encompassed static, and time series note data, coupled with static and time series table data. The temporal data underwent a preprocessing phase, padding to a 30-day interval, and segmenting into 3-day sub-sequences. These were fed into a long short-term memory (LSTM) network for sub-sequence representation. Multimodal attention gates were implemented for both static and temporal subsequence representations, culminating in fused representations. An attention-backtracking module was introduced for the latter, adept at capturing enduring dependencies in temporal fused representations. The concatenated results were channeled into an LSTM to yield the ultimate fused representation. Initially, two note modalities were designated as primary modes, and subsequently, the proposed fusion model was compared with comparative models including recent models such as Crossformer. The proposed model consistently exhibited superior predictive prowess in both tasks. Removing the attention-backtracking module led to performance decline. The proposed model consistently shows excellent predictive capabilities in both tasks. The proposed method not only effectively integrates data from the four modalities, but also has a good understanding of how to handle irregular time series data and lengthy clinical texts. An effective method is provided, which is expected to be more widely used in multimodal medical data representation.

16.
Sci Total Environ ; 917: 170434, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38278266

RESUMEN

Hydrothermal vents (HVs) and cold seeps (CSs) are typical deep-sea extreme ecosystems with their own geochemical characteristics to supply the unique living conditions for local communities. Once HVs or CSs stop emission, the dramatic environmental change would pose survival risks to deep-sea organisms. Up to now, limited knowledge has been available to understand the biological responses and adaptive strategy to the extreme environments and their transition from active to extinct stage, mainly due to the technical difficulties and lack of representative organisms. In this study, bathymodiolin mussels, the dominant and successful species surviving in diverse deep-sea extreme ecosystems, were collected from active and extinct HVs (Southwest Indian Ocean) or CSs (South China Sea) via two individual cruises. The transcriptomic analysis and determination of multiple biological indexes in stress defense and metabolic systems were conducted in both gills and digestive glands of mussels, together with the metagenomic analysis of symbionts in mussels. The results revealed the ecosystem- and tissue-specific transcriptional regulation in mussels, addressing the autologous adaptations in antioxidant defense, energy utilization and key compounds (i.e. sulfur) metabolism. In detail, the successful antioxidant defense contributed to conquering the oxidative stress induced during the unavoidable metabolism of xenobiotics commonly existing in the extreme ecosystems; changes in metabolic rate functioned to handle toxic matters in different surroundings; upregulated gene expression of sulfide:quinone oxidoreductase indicated an active sulfide detoxification in mussels from HVs and active stage of HVs & CSs. Coordinately, a heterologous adaptation, characterized by the functional compensation between symbionts and mussels in energy utilization, sulfur and carbon metabolism, was also evidenced by the bacterial metagenomic analysis. Taken together, a new insight was proposed that symbiotic bathymodiolin mussels would develop a "finetuning" strategy combining the autologous and heterologous regulations to fulfill the efficient and effective adaptations for successful survival.


Asunto(s)
Bivalvos , Respiraderos Hidrotermales , Animales , Ecosistema , Antioxidantes , Azufre , Sulfuros , Filogenia
17.
Res Sq ; 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38260360

RESUMEN

Understanding the spatial organization of nucleoporins (Nups) with intrinsically disordered domains within the nuclear pore complex (NPC) is crucial for deciphering eukaryotic nucleocytoplasmic transport. Leveraging high-speed 2D single-molecule tracking and virtual 3D super-resolution microscopy in live HeLa cells, we investigated the spatial distribution of all eleven phenylalanine-glycine (FG)-rich Nups within individual NPCs. Our study reveals a nuanced landscape of FG-Nup conformations and arrangements. Five FG-Nups are steadfastly anchored at the NPC scaffold, collectively shaping a central doughnut-shaped channel, while six others exhibit heightened flexibility, extending towards the cytoplasmic and nucleoplasmic regions. Intriguingly, Nup214 and Nup153 contribute to cap-like structures that dynamically alternate between open and closed states along the nucleocytoplasmic transport axis, impacting the cytoplasmic and nuclear sides, respectively. Furthermore, Nup98, concentrated at the scaffold region, extends throughout the entire NPC while overlapping with other FG-Nups. Together, these eleven FG-Nups compose a versatile, capped trichoid channel spanning approximately 270 nm across the nuclear envelope. This adaptable trichoid channel facilitates a spectrum of pathways for passive diffusion and facilitated nucleocytoplasmic transport. Our comprehensive mapping of FG-Nup organization within live NPCs offers a unifying mechanism accommodating multiple transport pathways, thereby advancing our understanding of cellular transport processes.

18.
Anticancer Drugs ; 35(3): 227-236, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38085677

RESUMEN

Ferroptosis is a novel form of cell death, which is distinguished from apoptosis and necrosis, and characterized by accumulation of lipid-based reactive oxygen species (ROS) in an iron-dependent manner. Erastin, a small molecule, was widely reported to trigger ferroptosis in various kinds of cancer cells, including pancreatic cancer cells by inducing ROS accumulation. However, how erastin treatment exerts cytotoxicity is not still fully understood. In this study, the effects of erastin in causing pancreatic cancer cell death via inducing ferroptosis and apoptosis are investigated. As expected, erastin treatment caused ROS accumulation, increase in iron concentration and non-apoptotic cell death, which is different from that of induced by apoptosis inducer, staurosporine. Interestingly, erastin treatment caused the upregulation of clusterin, which contributes to the regulation of malignant behaviors of pancreatic cancer, including preventing apoptosis and inducing chemoresistance. Without erastin treatment, overexpressed clusterin significantly promoted cell proliferation, which is consistent with its cytoprotective roles. After erastin treatment, overexpressed clusterin decreased erastin-induced ROS accumulation and cell death. By measuring iron concentration, reduced glutathione (GSH) and glutathione peroxidase 4 (GPX4), it is revealed that clusterin caused resistance to erastin-induced ferroptosis potentially via maintaining the enzymatic activity of GPX4, without disturbing GSH amount. Thus, ferroptosis inducer, erastin, may crosstalk with apoptotic cell death via regulating clusterin, indicating a more complex regulatory network between ferroptosis and apoptosis.


Asunto(s)
Adenocarcinoma , Clusterina , Ferroptosis , Neoplasias Pancreáticas , Piperazinas , Humanos , Adenocarcinoma/tratamiento farmacológico , Clusterina/metabolismo , Ferroptosis/efectos de los fármacos , Hierro/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Piperazinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral
19.
Anticancer Drugs ; 35(2): 140-154, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-37694833

RESUMEN

Dinaciclib, a cyclin-dependent kinase-5 (CDK5) inhibitor, has significant anti-tumor properties. However, the precise mechanism of dinaciclib requires further investigation. Herein, we investigated the anti-tumor functions and molecular basis of dinaciclib in pancreatic ductal adenocarcinoma (PDAC). PDAC and matched para-carcinoma specimens were collected from the patients who underwent radical resection. Immunohistochemistry was performed to assess CDK5 expression. Cell proliferation ability, migration, and invasion were measured using Cell Counting Kit-8, wound healing, and transwell assay, respectively. The cell cycle and apoptosis were assessed using flow cytometry. Gene expression was examined using RNA-seq and quantitative real-time PCR. Protein expression of proteins was measured by western blot analysis and immunofluorescence microscopy. Tumor-bearing mice were intraperitoneally injected with dinaciclib. CDK5 is highly expressed in PDAC. The expression level of CDK5 was significantly related to tumor size, T stage, and the American Joint Committee on Cancer stage. High CDK5 expression can predict poor survival in PDAC patients. In addition, the expression level of CDK5 might be an independent prognostic factor for PDAC patients. Dinaciclib inhibits the growth and motility of PDAC cells and induces apoptosis and cell cycle arrest in the G2/M phase. Mechanistically, dinaciclib down-regulated yes-associated protein (YAP) mRNA and protein expression by reducing ß-catenin expression. Moreover, dinaciclib significantly inhibited PDAC cell growth in vivo . Our findings reveal a novel anti-tumor mechanism of dinaciclib in which it decreases YAP expression by down-regulating ß-catenin at the transcriptional level rather than by activating Hippo pathway-mediated phosphorylation-dependent degradation.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Ratones , Animales , beta Catenina/metabolismo , Cateninas/genética , Cateninas/metabolismo , Cateninas/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Proliferación Celular , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Movimiento Celular
20.
Small ; 20(3): e2302550, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37726238

RESUMEN

The structural coloration of textiles with bionic photonic crystals (PCs) is expected to become a critical approach to the ecological coloration of textiles. Rapid and large-area preparation of PC structurally colored textiles can be achieved via self-assembly of high mass fractions of liquid photonic crystals (LPCs). However, the rapid and large-scale manufacturing of LPCs remains a challenge. In this work, the pH regulator is added in the process of emulsion polymerization to solve the problem of phase transformation caused by the thermal decomposition of the initiator to produce H+ , directly achieving 40 wt.% PS nanospheres in the dispersion. Then oligomers and small-molecule salts are removed from the system via dialysis, and the pre-crystallized LPC system is efficiently prepared. Adjusting the particle size and the mass fraction of nanospheres is shown to be an efficient way to control the optical properties of LPCs. The rapid and large-area preparation of PC structural color fabric and the patterned PC structural color fabric with an iridescent effect is implemented by using LPCs as the assembly intermediate. By constructing the encapsulation layer on the surface of the PC structural color fabric, the consistency of high structural stability and high color saturation of the PC is realized.

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