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1.
Talanta ; 275: 126156, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38692048

RESUMEN

The development of simple methods for the isolation and quantification of exosomes in biological samples is important. By using the typical two-dimensional (2D) nanomaterials, graphene oxide (GO), the present work first studied the interaction of liposomes with the nanocomposites formed by adsorbing HRP on the GO surface and found the presence of liposomes led to the release of HRP from the GO surface to the solution phase triggering the luminol-H2O2 chemiluminescence (CL) reaction to emit light. Benefiting from the similarity of exosomes to liposomes in both composition and morphology aspects, the GO-HRP nanocomposites with a mass ratio of 120:1 and 160:1 were employed for the quantitative detection of exosomes in 100-fold diluted serum samples. The whole detection process took about 15 min and as low as 3.2 × 102 particles µL-1 of exosomes could be sensitively detected. In addition to GO-HRP nanocomposites, the CL responses of other nanocomposites obtained from adsorbing HRP on other 2D nanomaterials such as layered MoS2 for exosomes were also tested. MoS2-HRP exhibited similar behavior and the LODs for the detection of exosomes were 5.8 × 102 particles µL-1. The proposed assays were a biomarker-independent quantitative method that achieved the quantification of exosomes in serum samples directly without an isolation process.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38656706

RESUMEN

To assess ChatGPT 4.0 (ChatGPT) and Gemini Ultra 1.0 (Gemini) large language models on NONMEM coding tasks relevant to pharmacometrics and clinical pharmacology. ChatGPT and Gemini were assessed on tasks mimicking real-world applications of NONMEM. The tasks ranged from providing a curriculum for learning NONMEM, an overview of NONMEM code structure to generating code. Prompts in lay language to elicit NONMEM code for a linear pharmacokinetic (PK) model with oral administration and a more complex model with two parallel first-order absorption mechanisms were investigated. Reproducibility and the impact of "temperature" hyperparameter settings were assessed. The code was reviewed by two NONMEM experts. ChatGPT and Gemini provided NONMEM curriculum structures combining foundational knowledge with advanced concepts (e.g., covariate modeling and Bayesian approaches) and practical skills including NONMEM code structure and syntax. ChatGPT provided an informative summary of the NONMEM control stream structure and outlined the key NONMEM Translator (NM-TRAN) records needed. ChatGPT and Gemini were able to generate code blocks for the NONMEM control stream from the lay language prompts for the two coding tasks. The control streams contained focal structural and syntax errors that required revision before they could be executed without errors and warnings. The code output from ChatGPT and Gemini was not reproducible, and varying the temperature hyperparameter did not reduce the errors and omissions substantively. Large language models may be useful in pharmacometrics for efficiently generating an initial coding template for modeling projects. However, the output can contain errors and omissions that require correction.

3.
J Cell Mol Med ; 28(8): e18304, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38652093

RESUMEN

Liver hepatocellular carcinoma (LIHC) is a significant global health issue with limited treatment options. In this study, single-cell RNA sequencing (scRNA-seq) data were used to explore the molecular mechanisms of LIHC development and identify potential targets for therapy. The expression of peroxisome proliferator-activated receptors (PPAR)-related genes was analysed in LIHC samples, and primary cell populations, including natural killer cells, T cells, B cells, myeloid cells, endothelial cells, fibroblasts and hepatocytes, were identified. Analysis of the differentially expressed genes (DEGs) between normal and tumour tissues revealed significant changes in gene expression in various cell populations. PPAR activity was evaluated using the 'AUCell' R software, which indicated higher scores in the normal versus the malignant hepatocytes. Furthermore, the DEGs showed significant enrichment of pathways related to lipid and glucose metabolism, cell development, differentiation and inflammation. A prognostic model was then constructed using 8 PPARs-related genes, including FABP5, LPL, ACAA1, PPARD, FABP4, PLIN1, HMGCS2 and CYP7A1, identified using least absolute shrinkage and selection operator-Cox regression analysis, and validated in the TCGA-LIHC, ICGI-LIRI and GSE14520 datasets. Patients with low-risk scores had better prognosis in all cohorts. Based on the expression of the eight model genes, two clusters of patients were identified by ConsensusCluster analysis. We also predicted small-molecule drugs targeting the model genes, and identified perfluorohexanesulfonic acid, triflumizole and perfluorononanoic acid as potential candidates. Finally, wound healing assay confirmed that PPARD can promote the migration of liver cancer cells. Overall, our study offers novel perspectives on the molecular mechanisms of LIHC and potential areas for therapeutic intervention, which may facilitate the development of more effective treatment regimens.


Asunto(s)
Carcinoma Hepatocelular , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , Simulación del Acoplamiento Molecular , Receptores Activados del Proliferador del Peroxisoma , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Pronóstico , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Receptores Activados del Proliferador del Peroxisoma/genética , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo
4.
Behav Sci (Basel) ; 14(4)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38667074

RESUMEN

The belief in online news has become a topical issue. Previous studies demonstrated the role emotion plays in fake news vulnerability. However, few studies have explored the effect of empathy on online news belief. This study investigated the relationship between trait empathy, state empathy, belief in online news, and the potential moderating effect of news type. One hundred and forty undergraduates evaluated 50 online news pieces (25 real, 25 fake) regarding their belief, state empathy, valence, arousal, and familiarity. Trait empathy data were collected using the Chinese version of the Interpersonal Reactivity Index. State empathy was positively correlated with affective empathy in trait empathy and believability, and affective empathy was positively correlated with believability. The influence of affective empathy on news belief was partially mediated by state empathy and regulated by news type (fake, real). We discuss the influence of empathy on online news belief and its internal processes. This study shares some unique insights for researchers, practitioners, social media users, and social media platform providers.

5.
BMC Biotechnol ; 24(1): 20, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637734

RESUMEN

BACKGROUND: Obtaining high-quality chloroplast genome sequences requires chloroplast DNA (cpDNA) samples that meet the sequencing requirements. The quality of extracted cpDNA directly impacts the efficiency and accuracy of sequencing analysis. Currently, there are no reported methods for extracting cpDNA from Erigeron breviscapus. Therefore, we developed a suitable method for extracting cpDNA from E. breviscapus and further verified its applicability to other medicinal plants. RESULTS: We conducted a comparative analysis of chloroplast isolation and cpDNA extraction using modified high-salt low-pH method, the high-salt method, and the NaOH low-salt method, respectively. Subsequently, the number of cpDNA copies relative to the nuclear DNA (nDNA ) was quantified via qPCR. As anticipated, chloroplasts isolated from E. breviscapus using the modified high-salt low-pH method exhibited intact structures with minimal cell debris. Moreover, the concentration, purity, and quality of E. breviscapus cpDNA extracted through this method surpassed those obtained from the other two methods. Furthermore, qPCR analysis confirmed that the modified high-salt low-pH method effectively minimized nDNA contamination in the extracted cpDNA. We then applied the developed modified high-salt low-pH method to other medicinal plant species, including Mentha haplocalyx, Taraxacum mongolicum, and Portulaca oleracea. The resultant effect on chloroplast isolation and cpDNA extraction further validated the generalizability and efficacy of this method across different plant species. CONCLUSIONS: The modified high-salt low-pH method represents a reliable approach for obtaining high-quality cpDNA from E. breviscapus. Its universal applicability establishes a solid foundation for chloroplast genome sequencing and analysis of this species. Moreover, it serves as a benchmark for developing similar methods to extract chloroplast genomes from other medicinal plants.


Asunto(s)
Genoma del Cloroplasto , Plantas Medicinales , ADN de Cloroplastos/genética , Plantas Medicinales/genética , Cloroplastos/genética , Mapeo Cromosómico , Filogenia
6.
China CDC Wkly ; 6(12): 230-234, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38633432

RESUMEN

What is already known about this topic?: Brucellosis, mainly caused by Brucella melitensis (B. melitensis), is regarded as a significant zoonotic disease in China. In Weihai, located at the eastern end of the Shandong Peninsula, brucellosis has been in a low epidemic phase for the past five years. What is added by this report?: This was the initial report of a brucellosis outbreak in the last five years. Strains of B. melitensis bv. 3 from Weihai and other cities showed a close genetic relationship, suggesting a potential common ancestry. What are the implications for public health practice?: Epidemiological investigations depend on standardized and effective molecular typing methods and analysis tools for public health laboratories to identify and trace outbreaks. Understanding the circulation patterns of livestock in free-range households in heavily affected areas is essential for controlling the spread of brucellosis.

7.
Artículo en Inglés | MEDLINE | ID: mdl-38625465

RESUMEN

This paper uses green innovation and environmental pollution as the mediating variables to construct a mediating effect model to investigate whether China's carbon emission trading policy can improve regional eco-efficiency by reducing regional environmental pollution and stimulating green innovation. This study is based on panel data from 30 provinces and municipalities directly under China's central government and autonomous regions from 2003 to 2019. The eco-efficiency of these provinces is measured using the super-efficiency DEA model and the difference-in-difference method (DID). The results show that (1) China's emission trading policy significantly improves regional ecological efficiency and the per capita GDP. The improvement can effectively improve regional ecological efficiency. (2) The mediating effect of green innovation and environmental pollution is significant. That is, China's carbon emission trading policy further improves regional ecological efficiency by stimulating more green innovation and reducing the synergy brought by environmental pollution. (3) There are differences in the feedback of this impact mechanism between different regions: It shows the characteristics of the western region being more significant than the eastern region. The central region has no significant effect. The research conclusion can provide a policy reference for the subsequent unified promotion of the construction of a carbon emission trading market nationwide and a theoretical basis for helping to achieve the "dual carbon" goal.

8.
Angew Chem Int Ed Engl ; : e202402312, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38578652

RESUMEN

The finite periodic arrangement of functional nanomaterials on the two-dimensional scale enables the integration and enhancement of individual properties, making them an important research topic in the field of tuneable nanodevices. Although layer-controllable lattices such as graphene have been successfully synthesized, achieving similar control over colloidal nanoparticles remains a challenge. DNA origami technology has achieved remarkable breakthroughs in programmed nanoparticle assembly. Based on this technology, we proposed a hierarchical assembly strategy to construct a universal DNA origami platform with customized layer properties, which we called 2.5-dimensional (2.5D) DNA origami crystals. Methodologically, this strategy divides the assembly procedure into two steps: 1) array synthesis, and 2) lattice synthesis, which means that the layer properties, including layer number, interlayer distance, and surface morphology, can be flexibly customized based on the independent designs in each step. In practice, these synthesized 2.5D crystals not only pioneer the expansion of the DNA origami crystal library to a wider range of dimensions, but also highlight the technological potential for templating 2.5D colloidal nanomaterial lattices.

9.
Membranes (Basel) ; 14(3)2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38535286

RESUMEN

The mass transfer behavior in a hollow fiber membrane module of membrane-based artificial organs (such as artificial liver or artificial kidney) were studied by numerical simulation. A new computational fluid dynamics (CFD) method coupled with K-K equation and the tortuous capillary pore diffusion model (TCPDM) was proposed for the simulations. The urea clearance rate predicted by the use of the numerical model agrees well with the experimental data, which verifies the validity of our numerical model. The distributions of concentration, pressure, and velocity in the hollow fiber membrane module were obtained to analyze the mass transfer behaviors of bilirubin and bovine serum albumin (BSA), and the effects of tube-side flow rate, shell-side flow rate, and fiber tube length on the bilirubin or BSA clearance rate were studied. The results show that the solute transport mainly occurred in the near inlet regions in the hollow fiber membrane module. Increasing the tube-side flow rate and the fiber tube length can effectively enhance the solute clearance rate, while the shell-side flow rate has less influence on the BSA clearance. The clearance of macromolecule BSA is dominated by convective solute transport, while the clearance of small molecule bilirubin is significantly affected by both convective and diffusive solute transport.

10.
Int J Mol Sci ; 25(6)2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38542280

RESUMEN

Cardiomyocyte survival is a critical contributing process of host adaptive responses to cardiovascular diseases (CVD). Cells of the cardiovascular endothelium have recently been reported to promote cardiomyocyte survival through exosome-loading cargos. Sphingosylphosphorylcholine (SPC), an intermediate metabolite of sphingolipids, mediates protection against myocardial infarction (MI). Nevertheless, the mechanism of SPC delivery by vascular endothelial cell (VEC)-derived exosomes (VEC-Exos) remains uncharacterized at the time of this writing. The present study utilized a mice model of ischemia/reperfusion (I/R) to demonstrate that the administration of exosomes via tail vein injection significantly diminished the severity of I/R-induced cardiac damage and prevented apoptosis of cardiomyocytes. Moreover, SPC was here identified as the primary mediator of the observed protective effects of VEC-Exos. In addition, within this investigation, in vitro experiments using cardiomyocytes showed that SPC counteracted myocardial I/R injury by activating the Parkin and nuclear receptor subfamily group A member 2/optineurin (NR4A2/OPTN) pathways, in turn resulting in increased levels of mitophagy within I/R-affected myocardium. The present study highlights the potential therapeutic effects of SPC-rich exosomes secreted by VECs on alleviating I/R-induced apoptosis in cardiomyocytes, thereby providing strong experimental evidence to support the application of SPC as a potential therapeutic target in the prevention and treatment of myocardial infarction.


Asunto(s)
Exosomas , Infarto del Miocardio , Daño por Reperfusión Miocárdica , Fosforilcolina/análogos & derivados , Esfingosina/análogos & derivados , Ratones , Animales , Daño por Reperfusión Miocárdica/metabolismo , Mitofagia , Miocitos Cardíacos/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/metabolismo , Células Endoteliales/metabolismo , Exosomas/metabolismo , Apoptosis
11.
J Nanobiotechnology ; 22(1): 106, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38468300

RESUMEN

Understanding the intricate nanoscale architecture of neuronal myelin during central nervous system development is of utmost importance. However, current visualization methods heavily rely on electron microscopy or indirect fluorescent method, lacking direct and real-time imaging capabilities. Here, we introduce a breakthrough near-infrared emissive curcumin-BODIPY derivative (MyL-1) that enables direct visualization of myelin structure in brain tissues. The remarkable compatibility of MyL-1 with stimulated emission depletion nanoscopy allows for unprecedented super-resolution imaging of myelin ultrastructure. Through this innovative approach, we comprehensively characterize the nanoscale myelinogenesis in three dimensions over the course of brain development, spanning from infancy to adulthood in mouse models. Moreover, we investigate the correlation between myelin substances and Myelin Basic Protein (MBP), shedding light on the essential role of MBP in facilitating myelinogenesis during vertebral development. This novel material, MyL-1, opens up new avenues for studying and understanding the intricate process of myelinogenesis in a direct and non-invasive manner, paving the way for further advancements in the field of nanoscale neuroimaging.


Asunto(s)
Compuestos de Boro , Curcumina , Animales , Ratones , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Neuronas , Microscopía Electrónica
13.
Front Immunol ; 15: 1352873, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38440727

RESUMEN

Background: Neoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular carcinoma (HCC) are currently lacking. This systematic review and meta-analysis aims to investigate the reliability of neoadjuvant immunotherapy's efficacy and safety in the context of HCC. Methods: A systematic search was conducted across PubMed (MEDLINE), EMBASE, the Web of Science, the Cochrane Library, and conference proceedings to identify clinical trials involving resectable HCC and neoadjuvant immunotherapy. Single-arm meta-analyses were employed to compute odds ratios and 95% confidence intervals (CIs). Heterogeneity analysis, data quality assessment, and subgroup analyses based on the type of immunotherapy drugs and combination therapies were performed. This meta-analysis is registered in PROSPERO (identifier CRD42023474276). Results: This meta-analysis included 255 patients from 11 studies. Among resectable HCC patients, neoadjuvant immunotherapy exhibited an overall major pathological response (MPR) rate of 0.47 (95% CI 0.31-0.70) and a pathological complete response (pCR) rate of 0.22 (95% CI 0.14-0.36). The overall objective response rate (ORR) was 0.37 (95% CI 0.20-0.69), with a grade 3-4 treatment-related adverse event (TRAE) incidence rate of 0.35 (95% CI 0.24-0.51). Furthermore, the combined surgical resection rate was 3.08 (95% CI 1.66-5.72). Subgroup analysis shows no significant differences in the efficacy and safety of different single-agent immunotherapies; the efficacy of dual ICIs (Immune Checkpoint Inhibitors) combination therapy is superior to targeted combined immunotherapy and monotherapy, while the reverse is observed in terms of safety. Discussion: Neoadjuvant immunotherapy presents beneficial outcomes in the treatment of resectable HCC. However, large-scale, high-quality experiments are warranted in the future to provide robust data support.


Asunto(s)
Carcinoma Hepatocelular , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Terapia Neoadyuvante , Reproducibilidad de los Resultados
14.
BMC Biol ; 22(1): 50, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38414012

RESUMEN

BACKGROUND: The formation and domestication of ornamental traits are influenced by various aspects, such as the recognition of esthetic values and cultural traditions. Camellia japonica is widely appreciated and domesticated around the world mainly due to its rich variations in ornamental traits. Ornamental camellias have a diverse range of resources, including different bud variations from Camellia spp. as well as inter- and intra- specific hybridization. Despite research on the formation of ornamental traits, a basic understanding of their genetics and genomics is still lacking. RESULTS: Here, we report the chromosomal-level reference genome of C. japonica through combining multiple DNA-sequencing technologies and obtain a high-density genetic linkage map of 4255 markers by sequencing 98 interspecific F1 hybrids between C. japonica and C. chekiangoleosa. We identify two whole-genome duplication events in C. japonica: one is a shared ancient γ event, and the other is revealed to be specific to genus Camellia. Based on the micro-collinearity analysis, we find large-scale segmental duplication of chromosome 8, resulting to two copies of the AGAMOUS loci, which may play a key role in the domestication of floral shapes. To explore the regulatory mechanisms of seasonal flowering, we have analyzed year-round gene expression patterns of C. japonica and C. azalea-a sister plant of continuous flowering that has been widely used for cross breeding. Through comparative analyses of gene co-expression networks and annual gene expression patterns, we show that annual expression rhythms of some important regulators of seasonal growth and development, including GIGANTEA and CONSTANS of the photoperiod pathway, have been disrupted in C. azalea. Furthermore, we reveal that the distinctive expression patterns of FLOWERING LOCUS T can be correlated with the seasonal activities of flowering and flushing. We demonstrate that the regulatory module involved in GIGANTEA, CONSTANS, and FLOWERING LOCUS T is central to achieve seasonality. CONCLUSIONS: Through the genomic and comparative genomics characterizations of ornamental Camellia spp., we propose that duplication of chromosomal segments as well as the establishment of gene expression patterns has played a key role in the formation of ornamental traits (e.g., flower shape, flowering time). This work provides a valuable genomic platform for understanding the molecular basis of ornamental traits.


Asunto(s)
Camellia , Estaciones del Año , Camellia/genética , Fitomejoramiento , Genómica , Flores/genética , Expresión Génica , Regulación de la Expresión Génica de las Plantas
15.
Mater Horiz ; 11(9): 2169-2179, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38384254

RESUMEN

Batteries taking conversion-type iron fluorides as energy-dense cathodes provide the possibility for the power electrification of the transportation and aviation industries. However, a safe and low-toxicity synthesis method for fluorides and the design of a compatible electrolyte formula are still challenging. Here, we propose a dual strategy of mild C-F scissoring fluorination and a local high-concentration electrolyte (LHCE) to enable highly reversible Li-Fe-F conversion batteries. A facile and safe scissoring strategy at a low temperature (95 °C) enables the preparation of a carbon-iron fluoride composite with a porous cubic cage-like structure. CFx plays a double role as a solid fluorination agent and an in situ conductive network after defluorination. The as-prepared fluoride cathode delivers a reversible capacity as high as 300 mA h g-1 over 100 cycles. The further LHCE strategy not only enhances the oxidation stable voltage of the electrolyte (>5 V) and the transference number of Li+ (0.74), but also realizes dual protection of the fluoride cathode and Li metal anode by facilitating the construction of robust cathode- and anode-electrolyte interfaces, respectively. The LHCE-assisted fluoride battery releases a higher reversible capacity of 335 mA h g-1 after 130 cycles. This work provides a solution to high-performance carbon-fluoride conversion cathodes by a synergetic effect of tailored synthesis, electroactive particle texture and electrolyte formula.

16.
Adv Sci (Weinh) ; 11(12): e2309133, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38225729

RESUMEN

The Ilizarov technique has been continuously innovated to utilize tensile stress (TS) for inducing a bone development-like regenerative process, aiming to achieve skeletal elongation and reconstruction. However, it remains uncertain whether this distraction osteogenesis (DO) process induced by TS involves the pivotal coupling of angiogenesis and osteogenesis mediated by type H endothelial cells (THECs). In this study, it is demonstrated that the Ilizarov technique induces the formation of a metaphysis-like architecture composed of THECs, leading to segmental bone regeneration during the DO process. Mechanistically, cell-matrix interactions-mediated activation of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) transcriptionally upregulates the expression of Notch1 and Delta-like ligand 4, which act as direct positive regulators of THECs phenotype, in bone marrow endothelial cells (BMECs) upon TS stimulation. Simultaneously, the Notch intracellular domain enhances YAP/TAZ activity by transcriptionally upregulating YAP expression and stabilizing TAZ protein, thus establishing the YAP/TAZ-Notch circuit. Additionally, TS-stimulated BMECs secrete exosomes enriched with vital molecules in this positive feedback pathway, which can be utilized to promote segmental bone defect healing, mimicking the therapeutic effects of Ilizarov technique. The findings advance the understanding of TS-induced segmental bone regeneration and establish the foundation for innovative biological therapeutic strategies aimed at activating THECs.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Exosomas , Proteínas Adaptadoras Transductoras de Señales/genética , Transducción de Señal , Transactivadores/metabolismo , Proteínas Señalizadoras YAP , Células Endoteliales/metabolismo , Exosomas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Factores de Transcripción/metabolismo , Regeneración Ósea
17.
Adv Sci (Weinh) ; 11(12): e2307388, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38233202

RESUMEN

Ferroptosis is a necrotic form of iron-dependent regulatory cell death. Estrogen withdrawal can interfere with iron metabolism, which is responsible for the pathogenesis of postmenopausal osteoporosis (PMOP). Here, it is demonstrated that estrogen withdrawal induces iron accumulation in the skeleton and the ferroptosis of osteocytes, leading to reduced bone mineral density. Furthermore, the facilitatory effect of ferroptosis of osteocytes is verified in the occurrence and development of postmenopausal osteoporosis is associated with over activated osteoclastogenesis using a direct osteocyte/osteoclast coculture system and glutathione peroxidase 4 (GPX4) knockout ovariectomized mice. In addition, the nuclear factor erythroid derived 2-related factor-2 (Nrf2) signaling pathway is confirmed to be a crucial factor in the ferroptosis of osteocytic cells. Nrf2 regulates the expression of nuclear factor kappa-B ligand (RANKL) by regulating the DNA methylation level of the RANKL promoter mediated by DNA methyltransferase 3a (Dnmt3a), which is as an important mechanism in osteocytic ferroptosis-mediated osteoclastogenesis. Taken together, this data suggests that osteocytic ferroptosis is involved in PMOP and can be targeted to tune bone homeostasis.


Asunto(s)
Ferroptosis , Osteoporosis Posmenopáusica , Ratones , Humanos , Animales , Femenino , Osteocitos/metabolismo , Osteoporosis Posmenopáusica/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrógenos/metabolismo , Hierro/metabolismo
18.
Int J Med Sci ; 21(1): 137-150, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38164350

RESUMEN

Background: Focal adhesion kinase (FAK) is activated by mechanical stimulation and plays a vital role in distraction osteogenesis (DO), a well-established but lengthy procedure for repairing large bone defects. Both angiogenesis and osteogenesis contribute to bone regeneration during DO. However, the effects of ZINC40099027 (ZN27), a potent FAK activator, on angiogenesis, osteogenesis, and bone regeneration in DO remain unknown. Methods: The angiogenic potential of human umbilical vein endothelial cells (HUVECs) was evaluated using transwell migration and tube formation assays. The osteogenic activity of bone marrow mesenchymal stem cells (BMSCs) was assessed using alkaline phosphatase (ALP) and alizarin red s (ARS) staining. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunofluorescence staining were used to assay angiogenic markers, osteogenic markers, and FAK-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. In vivo, a rat tibia DO model was established to verify the effects of ZN27 on neovascularization and bone regeneration using radiological and histological analyses. Results: ZN27 promoted the migration and angiogenesis of HUVECs. Additionally, ZN27 facilitated the osteogenic differentiation of BMSCs, as revealed by increased ALP activity, calcium deposition, and expression of osteogenesis-specific markers. The ERK1/2-specific inhibitor PD98059 significantly hindered the effects of ZN27, suggesting the participation of FAK-ERK1/2 signaling in ZN27-enhanced angiogenesis and osteogenesis. As indicated by improved radiological and histological features, ZN27 induced active angiogenesis within the distraction area and accelerated bone regeneration in a rat DO model. Conclusion: Our results show that ZN27 targets FAK-ERK1/2 signaling to stimulate both angiogenesis and osteogenesis, and ZN27 accelerates bone regeneration in DO, suggesting the therapeutic potential of ZN27 for repairing large bone defects in the mechanobiological environment during DO.


Asunto(s)
Osteogénesis por Distracción , Osteogénesis , Ratas , Humanos , Animales , Proteína Quinasa 3 Activada por Mitógenos , Sistema de Señalización de MAP Quinasas , Regeneración Ósea , Diferenciación Celular , Células Endoteliales de la Vena Umbilical Humana , Células Cultivadas
19.
Mater Horiz ; 11(2): 480-489, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-37965817

RESUMEN

Rechargeable fluoride ion batteries (FIBs) as an emerging anion shuttle system are attracting much attention due to their potential advantages in terms of energy density, cost and safety. A liquid electrolyte system enables the FIB operation at low or room temperature due to its higher ionic conductivity than that of a solid F-ion electrolyte. However, the insolubility of fluoride salts in aprotic solvents limits the development of liquid F-ion electrolytes. Although the boron-based anion acceptors (AAs) can facilitate the dissolution of F-ion salts, they are prone to lead to a tough desolvation process for F- due to strong Lewis acidity and therefore an inferior electrochemical performance. Here, a new non-boron AA (6-thioguanine) with moderate Lewis acidity is proposed to dissolve F- in the sulfone solvent. The ionic conductivity of the corresponding electrolytes reaches a level of mS cm-1 at room temperature. A model FIB coin cell is successfully operated with high conversion reaction reversibility based on the coupled defluorination/fluorination mechanism of electrodes, enabling a low overpotential of 0.36 V and a reversible capacity of 126 mA h g-1 after 40 cycles.

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