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JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.
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Ion preintercalation is an effective method for fine-tuning the electrochemical characteristics of electrode materials, thereby enhancing the performance of aqueous ammonium-ion hybrid supercapacitors (A-HSCs). However, much of the current research on ion preintercalation lacks controllability, and the underlying mechanisms remain unclear. In this study, we employ a two-step electrochemical activation approach, involving galvanostatic charge-discharge and cyclic voltammetry, to modulate the preintercalation of NH4+ in MnO2. An in-depth analysis of the electrochemical activation mechanism is presented. This two-step electrochemical activation approach endows the final MnO2/AC electrode with a high capacitance of 917.4 F g-1, approximately 2.4 times higher than that of original MnO2. Furthermore, the MnO2/AC electrode retains approximately 93.4% of its capacitance after 10 000 cycles at a current density of 25 mA cm-2. Additionally, aqueous A-HSC, comprising MnO2/AC and P-MoO3, achieves a maximum energy density of 87.6 Wh kg-1. This study offers novel insights into the controllable ion preintercalation approach via electrochemical activation.
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This study aims to investigate the relationship between bullying victimization and mobile phone addiction (MPA) among college students, taking into consideration the mediating role of self-control and the moderating role of physical activity. A self-report survey was administered to college students from 4 universities in Guangxi, Liaoning, and Hunan provinces in China. Participants were asked to report their experiences of bullying victimization, level of MPA, self-control, and physical activity. Descriptive statistics, correlation analysis, and regression analysis were conducted to analyze the data. Mediation and moderation models were subsequently established to examine the relationships between variables. The results indicated a positive correlation between bullying victimization and MPA among college students. Additionally, bullying victimization was negatively correlated with self-control. Bullying victimization significantly predicted MPA, and self-control partially mediated this relationship. Furthermore, physical activity moderated the association between bullying victimization and self-control among college students. The findings suggest that self-control plays a partial mediating role in the relationship between bullying victimization and MPA among college students. Moreover, physical activity weakens the association between bullying victimization and self-control. Therefore, promoting physical activity to reduce MPA among college students who have experienced bullying victimization is highly recommended.
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Acoso Escolar , Teléfono Celular , Víctimas de Crimen , Ejercicio Físico , Autocontrol , Estudiantes , Humanos , Masculino , Femenino , Estudiantes/psicología , Acoso Escolar/psicología , Universidades , Adulto Joven , Víctimas de Crimen/psicología , Autocontrol/psicología , China/epidemiología , Adulto , Conducta Adictiva/psicología , Adolescente , Encuestas y Cuestionarios , AutoinformeRESUMEN
Atmospheric water harvesting has attracted much attention because of its potential to escalate the global freshwater shortage. However, the water collection efficiency is hindered by the trade-off between fast droplet nucleating and rapid droplet dripping due to the opposite requirements in the chemistry and the morphology of surfaces. Herein, the hierarchical porous composite film (ZIF-8@PVDF/PMMA, HPCF) with superhydrophobicity is designed for highly efficient and stable water harvesting. It indicates that the HPCF film has a large water contact angle (WCA) of 155.50° and ultralow sliding angle (SA) of 2°, exhibiting the self-cleaning function. Significantly, it is demonstrated that the water collection efficiency of HPCF can achieve 1.13 g·cm-2·h-1, which is much higher than the value of the blank sample, as well as most of the reported values. It is attributed to the hierarchical porous structure with the ZIF-8 crystals enhancing the surface roughness and endowing the film with the hydrophilic/superhydrophobic regions. This design promotes an optimal balance between droplet nucleation and shedding, significantly enhancing the water harvesting efficiency. Consequently, this work introduces an effective approach for water collection materials suitable for fog/mist conditions and provides an effective solution for the foggy area with water scarcity, demonstrating significance for advancing research aimed at mitigating the worldwide water shortage.
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Background: Pancreatic neuroendocrine neoplasm (pNEN) poses significant challenges in clinical management due to their heterogeneity and limited treatment options. In this study, we investigated the potential of simvastatin (SIM) as an anti-tumor agent in pNEN. Methods: We conducted cell culture experiments using QGP-1 and BON-1 cell lines and assessed cell viability, proliferation, migration, and invasion following SIM treatment. To further validate our findings, we performed in vivo experiments using a mouse xenograft model. Additionally, we investigated the underlying molecular mechanisms by analyzing changes in cell cycle progression, apoptosis, and signaling pathways. Results: SIM treatment suppresses pNEN growth both in vitro and in vivo, and led to G1 phase arrest in QGP-1 cells. In contrast, SIM affected both the G1-S and G2-M phase transitions in the BON-1 cell line and induced apoptosis, indicating diverse mechanisms of action. Furthermore, SIM treatment resulted in decreased expression of mutant p53 (mutp53) in BON-1 cells, suggesting a potential therapeutic strategy targeting mutp53. Modulation of the MAPK pathway was also implicated in QGP-1 cells. Conclusions: Our study highlights SIM as a promising candidate for pNEN treatment by inducing cell cycle arrest or apoptosis, potentially through the p53 and MAPK pathways. Further research is warranted to fully elucidate SIM's mechanisms of action and evaluate its therapeutic potential in clinical settings.
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Background: Stereotactic body radiotherapy (SBRT) combined immunotherapy has a synergistic effect on patients with stage IV tumors. However, the efficacy and prognostic factors analysis of SBRT combined immunotherapy for patients with pulmonary oligometastases have rarely been reported in the studies. The purpose of this study is to explore the efficacy and prognostic factors analysis of SBRT combined immunotherapy for patients with oligometastatic lung tumors. Methods: A retrospective analysis was conducted on 43 patients with advanced tumors who received SBRT combined with immunotherapy for pulmonary oligometastases from October 2018 to October 2021. Local control (LC), progression-free survival (PFS), and overall survival (OS) were assessed using the Kaplan-Meier method. Univariate and multivariate analyses of OS were performed using the Cox regression model, and the P value <0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve of neutrophil-to-lymphocyte ratio (NLR) after SBRT was generated. Spearman correlation analysis was used to determine the relationship of planning target volume (PTV) with absolute lymphocyte count (ALC) before and after SBRT and with neutrophil count (NE) after SBRT. Additionally, linear regression was used to examine the relationship between ALC after SBRT and clinical factors. Results: A total of 43 patients with pulmonary oligometastases receiving SBRT combined with immunotherapy were included in the study. The change in NLR after SBRT was statistically significant (P<0.001). At 1 and 2 years, respectively, the LC rates were 90.3% and 87.5%, the OS rates were 83.46% and 60.99%, and the PFS rates were 69.92% and 54.25%, with a median PFS of 27.00 (17.84-36.13) months. Univariate and multivariate Cox regression analyses showed that a shorter interval between radiotherapy and immunization [≤21 days; hazard ratio (HR) =1.10, 95% confidence interval (CI): 0.06-0.89; P=0.02] and a low NLR after SBRT (HR =0.24, 95% CI: 1.01-1.9; P=0.03) were associated with improved OS. The ROC curve identified 4.12 as the cutoff value for predicting OS based on NLR after SBRT. NLR after SBRT ≤4.12 significantly extended OS compared to NLR after SBRT >4.12 (log-rank P=0.001). Spearman correlation analysis and linear regression analysis showed that PTV was negatively correlated with ALC after SBRT. Conclusions: Our preliminary research shows that SBRT combined with immunotherapy has a good effect, and NLR after SBRT is a poor prognostic factor for OS. Larger PTV volume is associated with decreased ALC after SBRT.
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Background: Natural killer (NK) cells are proposed to participate in coronary artery disease (CAD) development. However, little is known about how CAD patients' NK cells respond to different stimulatory factors in terms of proliferation capability. Methods and results: Twenty-nine CAD patients' peripheral blood NK cells were isolated and individually treated with IL-2, IL-12, IL-15, IL-18, IL-21, cortisone acetate, hydrocortisone, or ascorbic acid for 36 hours, followed by cell cycle analysis using flow cytometry. The ratio of S and G2/M phase cell number to total cell number was defined as a proliferation index (PrI) and used for proliferative capability indication. The results showed that these eight factors resulted in different life cycle changes in the 29 NK cell samples. Remarkably, 28 out of 29 NK cell samples showed an obvious increase in PrI upon ascorbic acid treatment. The serum lactate dehydrogenase (LDH) level of the 29 CAD patients was measured. The results showed a negative correlation between serum LDH level and the CAD patients' NK cell PrI upon stimulation of interleukins, but not the non-interleukin stimulators. Consistently, a retrospective analysis of 46 CAD patients and 32 healthy donors showed that the circulating NK cell number negatively correlated with the serum LDH level in CAD patients. Unexpectedly, addition of LDH to NK cells significantly enhanced the production of IFN-γ, IL-10 and TNF-α, suggesting a strong regulatory role on NK cell's function. Conclusion: Ascorbic acid could promote the proliferation of the CAD patients' NK cells; LDH serum level may function as an indicator for NK cell proliferation capability and an immune-regulatory factor.
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Proliferación Celular , Enfermedad de la Arteria Coronaria , Citocinas , Células Asesinas Naturales , L-Lactato Deshidrogenasa , Humanos , Células Asesinas Naturales/inmunología , Enfermedad de la Arteria Coronaria/inmunología , Enfermedad de la Arteria Coronaria/sangre , Masculino , Femenino , Persona de Mediana Edad , L-Lactato Deshidrogenasa/sangre , Anciano , Células CultivadasRESUMEN
Tumor proliferation and metastasis are intricately linked to blood vessel formation, with vascular endothelial growth factor (VEGF) playing a pivotal role in orchestrating angiogenesis throughout tumor progression. Pseudolaric acid B (PAB) has emerged as a potent inhibitor of tumor cell proliferation, migration, and angiogenesis. In efforts to enhance its efficacy, 37 derivatives of PAB were synthesized and assessed for their capacity to suppress VEGF secretion in SiHa cells under hypoxic conditions. Notably, majority of these derivatives exhibited significant inhibition of VEGF protein secretion without inducing cytotoxicity. Among them, compound M2 displayed the most potent inhibitory activity, with an IC50 value of 0.68 µM, outperforming the lead compound PAB (IC50 = 5.44 µM). Compound M2 not only curbed the migration and angiogenesis of HUVECs under hypoxic conditions but also hindered the invasion of SiHa cells. Mechanistic investigations unveiled that compound M2 may impede the accumulation and nuclear translocation of hypoxia-inducible factor 1α (HIF-1α) in SiHa cells, thereby downregulating VEGF expression. This inhibitory effect on HIF-1α was corroborated by experiments utilizing the protease inhibitor MG-132 and protein synthesis inhibitor CHX, indicating that compound M2 diminishes HIF-1α levels by reducing its synthesis. Furthermore, compound M2 was observed to modulate the PI3K/AKT/mTOR and MAPK signaling pathways in tumor cells, thereby regulating HIF-1α translation and synthesis. In vivo studies demonstrated that compound M2 exhibited low toxicity and effectively curbed tumor growth. Immunohistochemistry analyses validated that compound M2 effectively suppressed the expression of HIF-1α and VEGF in tumor tissues, underscoring its potential as a promising therapeutic agent for targeting tumor angiogenesis.
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Inhibidores de la Angiogénesis , Antineoplásicos , Proliferación Celular , Diterpenos , Diseño de Fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Factor A de Crecimiento Endotelial Vascular , Humanos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/síntesis química , Inhibidores de la Angiogénesis/química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , Diterpenos/farmacología , Diterpenos/síntesis química , Diterpenos/química , Transducción de Señal/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Animales , Movimiento Celular/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismoRESUMEN
Supramolecular polymers are typical self-assemblies, in which repeating monomer units are bonded together with dynamic and reversible noncovalent interactions. Supramolecular polymers can combine the advantages of polymer science and supramolecular chemistry. Aggregation-induced emission (AIE) means that a molecule remains faintly emissive in the dispersed state but intensively luminescent in a highly aggregated state. AIE has brought new opportunities and further development potential to the field of polymeric chemistry. The integration of AIE luminogens with supramolecular interactions can provide new vitality for supramolecular polymers. Therefore, it is essential for scientists to understand the preparation and applications of AIE-active supramolecular polymers. This review focuses on the recent advanced progress in the preparation of AIE-active supramolecular polymers. In addition, we summarize the newly developed supramolecular polymers with an AIE nature and their applications in chemical sensing, and in vitro and in vivo imaging, as well as the visualization of their structure and properties. Finally, the development trends and challenges of AIE-active supramolecular polymers are prospected.
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Ammonium dinitramide (ADN), as a novel and environmentally friendly oxidizer, has strong hygroscopicity when exposed to high-humidity air, which seriously hinders its application in solid propellants. Modification of oxidizers by cocrystallization is an effective strategy to improve the hygroscopicity of energetic components. In this paper, the theoretical simulation of ADN/CL-20 cocrystals was developed via a directional hydrogen bonding design to establish a cocrystal with improved hygroscopicity. Intermolecular interaction analyses reveal that hydrogen bonds and van der Waals interactions synergistically lead to the formation of cocrystals. The ADN/CL-20 cocrystal was prepared experimentally by the spray drying self-assembly technique, and the corresponding thermal analysis and sensitivity properties were conducted to illustrate the thermal stability and high safety. Furthermore, the critical relative humidity (CRH) measurement was carried out to evaluate the hygroscopicity of the cocrystal, exhibiting a certain degree of antihygroscopic effect with a CRH of 65%. The hydrogen bonds formed between ADN and CL-20 saturate the ammonium ions of ADN, further preventing ADN from absorbing water molecules in the air. The ADN/CL-20 cocrystal has high specific impulse characteristics (Isp: 272.6 s). Accordingly, this work clearly demonstrates that the ADN/CL-20 cocrystal is expected to be used in a solid propellant to make up for the deficiency of the ADN oxidizer.
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The aim of this study was to investigate whether the protective effect of 2-deoxyglucose (2-DG) on lung ischemia/reperfusion (I/R) injury is mediated by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated pyroptosis in rats. Male Sprague-Dawley rats were randomly divided into control group, 2-DG group, lung I/R injury group (I/R group) and 2-DG+I/R group. 2-DG (0.7 g/kg) was intraperitoneally injected 1 h prior to lung ischemia. The tissue structure was measured under light microscope. Lung injury parameters were detected. The contents of malondialdehyde (MDA), myeloperoxidase (MPO) and lactate were determined by commercially available kits. ELISA was used to detect the levels of IL-1ß and IL-18. Western blot, qRT-PCR and immunofluorescence staining were used to measure the expression changes of glycolysis and pyroptosis related indicators. The results showed that there was no significant difference in the parameters between the control group and the 2-DG group. However, the lung injury parameters, oxidative stress response, lactic acid content, IL-1ß, and IL-18 levels were significantly increased in the I/R group. The protein expression levels of glycolysis and pyroptosis related indicators including hexokinase 2 (HK2), pyruvate kinase 2 (PKM2), NLRP3, Gasdermin superfamily member GSDMD-N, cleaved-Caspase1, cleaved-IL-1ß and cleaved-IL-18, and the gene expression levels of HK2, PKM2 and NLRP3 were markedly up-regulated in the I/R group compared with those in the control group. The expression of HK2 and NLRP3 was also increased detected by immunofluorescence staining. Compared with the I/R group, the 2-DG+I/R group exhibited significantly improved alveolar structure and inflammatory infiltration, reduced lung injury parameters, and decreased expression of glycolysis and pyroptosis related indicators. These results suggest that 2-DG protects against lung I/R injury possibly by inhibiting NLRP3-mediated pyroptosis in rats.
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Desoxiglucosa , Pulmón , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Ratas Sprague-Dawley , Daño por Reperfusión , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Masculino , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Ratas , Pulmón/metabolismo , Pulmón/patología , Desoxiglucosa/farmacología , Interleucina-1beta/metabolismo , Interleucina-18/metabolismo , Lesión Pulmonar/metabolismo , Lesión Pulmonar/prevención & control , Lesión Pulmonar/etiología , Estrés OxidativoRESUMEN
A circular non-touch mode capacitive pressure sensor can operate in both transverse and normal uniform loading modes, but the elastic behavior of its movable electrode plate is different under the two different loading modes, making its input-output analytical relationships between pressure and capacitance different. This suggests that when such a sensor operates, respectively, in transverse and normal uniform loading modes, the theory of its numerical design and calibration is different, in other words, the theory for the transverse uniform loading mode (available in the literature) cannot be used as the theory for the normal uniform loading mode (not yet available in the literature). In this paper, a circular non-touch mode capacitive pressure sensor operating in normal uniform loading mode is considered. The elastic behavior of the movable electrode plate of the sensor under normal uniform loading is analytically solved with the improved governing equations, and the improved analytical solution obtained can be used to mathematically describe the movable electrode plate with larger elastic deflections, in comparison with the existing two analytical solutions in the literature. This provides a larger technical space for developing the circular non-touch mode capacitive pressure sensors used for measuring the static gas pressure (belonging to normal uniform loading).
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Inflammatory bowel disease (IBD) refers to long-term medical conditions that involve inflammation of the digestive tract, and the global incidence and prevalence of IBD are on the rise. Gut microbes play an important role in maintaining the intestinal health of the host, and the occurrence, development, and therapeutic effects of IBD are closely related to the structural and functional changes of gut microbes. Published studies have shown that the natural products from traditional Chinese medicine have direct or indirect regulatory impacts on the composition and metabolism of the gut microbes. In this review, we summarize the research progress of several groups of natural products, i.e., flavonoids, alkaloids, saponins, polysaccharides, polyphenols, and terpenoids, for the therapeutic activities in relieving IBD symptoms. The role of gut microbes and their intestinal metabolites in managing the IBD is presented, with focusing on the mechanism of action of those natural products. Traditional Chinese medicine alleviated IBD symptoms by regulating gut microbes, providing important theoretical and practical basis for the treatment of variable inflammatory intestinal diseases.
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OBJECTIVES: To investigate whether high concentration iodinated contrast media (CM), compared with low concentration CM, could reduce pain and discomfort levels in patients who had level II and III venous conditions. METHODS: This prospective, single-center study enrolled patients who had level II and III venous conditions and underwent abdominal contrast-enhanced CT scan between July 2021 and February 2022. The venous condition to establish peripheral venous access for CM injection was graded using the Intravenous Access Scoring system, of which level II and III indicated poor venous condition and difficult venous access. Patients received iomeprol 400 in high concentration group and ioversol 320 in low group at an identical iodine delivery rate of 1.12 gI/s. The primary outcomes were pain and comfort levels. The secondary outcomes included adverse events and image quality. Patients rated pain intensity via Numerical Rating Scale and comfort level via Visual Analogue Scale with higher scores indicating higher levels of pain and discomfort. Quantitative and qualitative image assessment were compared between two groups. Continuous variables were compared using Student's t test or Mann-Whitney U test. Categorical variables were compared using χ2 test, χ2 test for trend or Fisher's exact test. RESULTS: A total of 206 patients (mean age, 60.13 ± 12.14 years; 81 males) were included with 99 in the high concentration group and 107 in the low concentration group. The high group had significantly lower pain scores (median 1 [IQR: 0-2] vs 2 (IQR 2-4), p < 0.001) and comfort scores (1 [IQR: 0-3] vs 3 [IQR: 2-5], p < 0.001) than the low group. Incidence of CM extravasation did not significantly differ (1.0 % vs 4.5 %, p = 0.214). No hypersensitivity reaction was observed. Qualitative assessment showed higher clarity scores of intrahepatic hepatic artery and portal vein in the high group. Quantitative assessment results were comparable between two groups. CONCLUSION: High concentration iodinated CM could lower pain intensity and improve comfort levels without comprising image quality of CT scan. High concentration CM is a preferable choice in patients with poor venous conditions during contrast-enhanced CT scan.
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Medios de Contraste , Yopamidol , Dimensión del Dolor , Tomografía Computarizada por Rayos X , Humanos , Medios de Contraste/efectos adversos , Medios de Contraste/administración & dosificación , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía Computarizada por Rayos X/métodos , Yopamidol/análogos & derivados , Yopamidol/administración & dosificación , Yopamidol/efectos adversos , Ácidos Triyodobenzoicos/efectos adversos , Ácidos Triyodobenzoicos/administración & dosificación , Anciano , Radiografía Abdominal/métodos , Dolor Abdominal/diagnóstico por imagen , Dolor Abdominal/prevención & control , Dolor Abdominal/inducido químicamenteRESUMEN
One-lung ventilation (OLV) during thoracic surgery often leads to post-operative complications, yet effective pharmacological interventions are lacking. This study reports a baicalin-based metal-coordination nanomedicine with disulfiram (DSF) co-loading to address one-lung ventilation-induced lung injury and reperfusion injury (OLV-LIRI). Baicalin, known for its robust antioxidant properties, suffers from poor water solubility and stability. Leveraging nanotechnology, baicalin's coordination is systematically explored with seven common metal ions, designing iron/copper-mediated binary coordination nanoparticles to overcome these limitations. The self-assembled nanoparticles, primarily formed through metal coordination and π-π stacking forces, encapsulated DSF, ensuring high colloidal stability in diverse physiological matrices. Upon a single-dose administration via endotracheal intubation, the nanoparticles efficiently accumulate in lung tissues and swiftly penetrate the pulmonary mucosa. Intracellularly, baicalin exhibits free radical scavenging activity to suppress inflammation. Concurrently, the release of Cu2+ and DSF enables the in situ generation of CuET, a potent inhibitor of cell pyroptosis. Harnessing these multifaceted mechanisms, the nanoparticles alleviate lung injury symptoms without notable toxic side effects, suggesting a promising preventive strategy for OLV-LIRI.
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An electrochemical aptasensor was developed by utilizing a DNA walker driven by catalytic hairpin assembly (CHA) with kanamycin as the model analyte. Kanamycin bound to the aptamer, causes the release of DNA walker, triggers the CHA reaction, leads to the cyclic movement of the walker's long arm, and results in cascade amplification of the signal. The guanine-rich sequences of the double-stranded products produced by CHA were folded to form G-quadruplex structures, with electrochemical active molecules Hemin embedded, forms G-quadruplex/Hemin complexes in situ on the electrode surface, thereby achieving sensitive, efficient, and label-free detection of kanamycin with a limit of detection (LOD) of 0.27 pM (S/N = 3). Meaningfully, the aptasensor demonstrated high sensitivity and reliability in the detection of kanamycin in milk and livestock wastewater samples, suggesting that it has great potential for application in detecting antibiotics in food products and water samples from the environment.
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Antibacterianos , Aptámeros de Nucleótidos , Técnicas Biosensibles , Técnicas Electroquímicas , G-Cuádruplex , Hemina , Kanamicina , Límite de Detección , Leche , Aptámeros de Nucleótidos/química , Kanamicina/análisis , Antibacterianos/análisis , Técnicas Electroquímicas/métodos , Técnicas Biosensibles/métodos , Leche/química , Hemina/química , Animales , Aguas Residuales/análisis , ADN/química , Catálisis , ElectrodosRESUMEN
Xeroderma pigmentosum is a rare autosomal recessive genodermatoses characterized by a deficiency in nucleotide excision repair. Erythropoietic protoporphyria is a rare inherited metabolic disease caused by the perturbation of heme. Xeroderma pigmentosum-erythropoietic protoporphyria is exceedingly rare. Hereby, we firstly report a young Chinese patient of xeroderma pigmentosum Group A with erythropoietic protoporphyria carrying an XPA Met214AsnfsTer7 frameshift mutation and a homozygous splicing mutation, c.315-48T>C, in the proband's intron3 of FECH.
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Ferroquelatasa , Protoporfiria Eritropoyética , Xerodermia Pigmentosa , Humanos , Protoporfiria Eritropoyética/genética , Protoporfiria Eritropoyética/complicaciones , Xerodermia Pigmentosa/genética , Xerodermia Pigmentosa/complicaciones , Ferroquelatasa/genética , Masculino , Proteína de la Xerodermia Pigmentosa del Grupo A/genética , Mutación , Pueblo Asiatico/genética , Femenino , China , Mutación del Sistema de Lectura , Pueblos del Este de AsiaRESUMEN
OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION: The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
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BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEJ) is increasing, and with poor prognosis. Lymph node status (LNs) is particularly important for planning treatment and evaluating the prognosis of patients with AEJ. However, the use of radiomic based on enhanced computed tomography (CT) to predict the preoperative lymph node metastasis (PLNM) status of the AEJ has yet to be reported. PURPOSE: We sought to investigate the value of radiomic features based on enhanced CT in the accurate prediction of PLNM in patients with AEJ. METHODS: Clinical features and enhanced CT data of 235 patients with AEJ from October 2017 to May 2023 were retrospectively analyzed. The data were randomly assigned to the training cohort (n = 164) or the external testing cohort (n = 71) at a ratio of 7:3. A CT-report model, clinical model, radiomic model, and radiomic-clinical combined model were developed to predict PLNM in patients with AEJ. Univariate and multivariate logistic regression were used to screen for independent clinical risk factors. Least absolute shrinkage and selection operator (LASSO) regression was used to select the radiomic features. Finally, a nomogram for the preoperative prediction of PLNM in AEJ was constructed by combining Radiomics-score and clinical risk factors. The models were evaluated by area under the receiver operating characteristic curve (AUC-ROC), calibration curve, and decision curve analyses. RESULTS: A total of 181 patients (181/235, 77.02%) had LNM. In the testing cohort, the AUC of the radiomic-clinical model was 0.863 [95% confidence interval (CI) = 0.738-0.957], and the radiomic model (0.816; 95% CI = 0.681-0.929), clinical model (0.792; 95% CI = 0.677-0.888), and CT-report model (0.755; 95% CI = 0.647-0.840). CONCLUSION: The radiomic-clinical model is a feasible method for predicting PLNM in patients with AEJ, helping to guide clinical decision-making and personalized treatment planning.