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Recent progress in stem cell therapy has demonstrated the therapeutic potential of intravenous stem cell infusions for treating the life-threatening lung disease of pulmonary fibrosis (PF). However, it is confronted with limitations, such as a lack of control over cellular function and rapid clearance by the host after implantation. In this study, we developed an innovative PF therapy through tracheal administration of microfluidic-templated stem cell-laden microcapsules, which effectively reversed the progression of inflammation and fibrotic injury. Our findings highlight that hydrogel microencapsulation can enhance the persistence of donor mesenchymal stem cells (MSCs) in the host while driving MSCs to substantially augment their therapeutic functions, including immunoregulation and matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) remodeling. We revealed that microencapsulation activates the MAPK signaling pathway in MSCs to increase MMP expression, thereby degrading overexpressed collagen accumulated in fibrotic lungs. Our research demonstrates the potential of hydrogel microcapsules to enhance the therapeutic efficacy of MSCs through cell-material interactions, presenting a promising yet straightforward strategy for designing advanced stem cell therapies for fibrotic diseases.
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Matriz Extracelular , Factores Inmunológicos , Fibrosis Pulmonar , Células Madre , Cápsulas/química , Factores Inmunológicos/química , Factores Inmunológicos/farmacología , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/terapia , Células Cultivadas , Humanos , Matriz Extracelular/química , Microfluídica , Supervivencia Celular/efectos de los fármacos , Hidrogeles/química , Masculino , Animales , Ratones , Ratones Endogámicos C57BL , Metaloproteinasas de la Matriz/metabolismoRESUMEN
Latexin (LXN) is abundant in macrophages and plays critical roles in inflammation. Much is known about macrophages in atherosclerosis, the role of macrophage LXN in atherosclerosis has remained elusive. Here, the expression of LXN in human and mouse atherosclerotic lesions was examined by immunofluorescence and immunohistochemistry. LXN knockout and LXN/ApoE double-knockout mice were generated to evaluate the functions of LXN in atherosclerosis. Bone marrow transplantation (BMT) experimentation was carried out to determine whether macrophage LXN regulates atherosclerosis. We found that LXN is enriched in human and murine atherosclerotic lesions, mainly localized to macrophages. LXN deletion ameliorated atherosclerosis in ApoE-/- mice. BMT demonstrate that deletion of LXN in bone marrow protects ApoE-/- mice against atherosclerosis. Mechanistically, we found that LXN targets and inhibits JAK1 in macrophages. LXN deficiency stimulates the JAK1/STAT3/ABC transporter pathway, thereby enhancing the anti-inflammatory and anti-oxidant phenotype, cholesterol efflux, subsequently minimizing foam cell formation and atherosclerosis. Gene therapy by treatment of atherosclerotic mice with adeno-associated virus harbouring LXN-depleting shRNA attenuated the disease phenotype. In summary, our study provides new clues for the role of LXN in the pathological regulation of atherosclerosis, and determines that LXN is a target for preventing atherosclerosis, which may be a potential new anti-atherosclerosis therapeutic target.
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Aterosclerosis , Células Espumosas , Macrófagos , Fenotipo , Animales , Aterosclerosis/patología , Aterosclerosis/metabolismo , Aterosclerosis/genética , Células Espumosas/metabolismo , Células Espumosas/patología , Ratones , Humanos , Macrófagos/metabolismo , Diferenciación Celular , Ratones Noqueados , Ratones Endogámicos C57BL , Masculino , Apolipoproteínas E/deficiencia , Apolipoproteínas E/metabolismo , Apolipoproteínas E/genética , Factor de Transcripción STAT3/metabolismoRESUMEN
BACKGROUND: This study aimed to explore the clinical significance of ruxolitinib and its effects on the proliferation and apoptosis of human erythroleukemia (HEL) cells and the expression of immune checkpoint molecules programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and regulatory T cells (Tregs) in HEL cells and JAK2 V617F-positive patients with myeloproliferative neoplasms (MPNs). METHODS: JAK2 V617F-positive patients with MPNs admitted to the Baoding No. 1 Hospital from January 2016 to September 2023 were recruited, including 30 patients for the newly diagnosed group and 10 for the treatment group. Additionally, 15 healthy volunteers were selected as the control group. JAK2 V617F mutation was detected by using fluorescence quantitative PCR, and the expression levels of phosphorylated JAK2 (p-JAK2), PD-1, and PD-L1 in fresh bone marrow were examined by immunohistochemistry. HEL cells were treated with ruxolitinib at different concentrations (0, 50, 100, 250, 500, and 1,000 nmol/L). Cell viability was detected by CCK-8 assay. The mRNA expression levels of JAK2, PD-1, and PD-L1 were determined by using fluorescence quantitative PCR. The protein expression of p-JAK2 was detected by Western blot and those of PD-1 and PD-L1 were evaluated by flow cytometry. The expression of PD-1, PD-L1, and Tregs after the 48-hour co-culture of primary bone marrow cells and HEL cells were also analyzed by flow cytometry. RESULTS: In the newly diagnosed group, the bone marrow myeloid cells highly expressed p-JAK2, PD-1, and PD-L1. The Tregs expression in their peripheral blood increased and was significantly higher than those in the treatment and control groups (all p < 0.05). Ruxolitinib at different concentrations could inhibit the proliferation of HEL cells and was positively correlated with treatment time and dose. Additionally, ruxolitinib could reduce p-JAK2, PD-1, and PD-L1 expression in HEL cells and Tregs expression. CONCLUSIONS: Ruxolitinib reduces the expression of p-JAK2, PD-1, and PD-L1 in JAK2 V617F-positive cells by specifically inhibiting the JAK2 signaling pathway, thereby suppressing the progression of MPNs.
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Antígeno B7-H1 , Janus Quinasa 2 , Trastornos Mieloproliferativos , Nitrilos , Pirazoles , Pirimidinas , Humanos , Pirazoles/farmacología , Pirazoles/uso terapéutico , Janus Quinasa 2/genética , Janus Quinasa 2/metabolismo , Nitrilos/farmacología , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/inmunología , Trastornos Mieloproliferativos/metabolismo , Adulto , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Anciano , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , MutaciónRESUMEN
Background: The prevalence of gene fusion is extremely low in unselected patients with colorectal cancer (CRC). Published data on gene fusions are limited by relatively small sample sizes, with a primary focus on Western populations. This study aimed to analyse actionable gene fusions in a large consecutive Chinese CRC population. Methods: This study included 5,534 consecutive CRC patients from the Genecast database. Genomic profiling was performed using a panel of 769 cancer-related genes. Data for 34 CRC patients with actionable gene fusions were also collected from cBioPortal and ChimerSeq. Results: Among 5,534 CRC patients, 54 (0.98%) had actionable gene fusions, with NTRK1/2/3 being the most common fusion (0.38%), accounting for 38.9% (21/54) of those with fusions. Actionable gene fusion enrichment was higher in patients with microsatellite instability-high (MSI-H) (6.7% vs. 0.5%, P < 0.001), RAS/BRAF wildtype (2.0% vs. 0.2%, P < 0.001) and RNF43 mutation (7.7% vs. 0.4%, P < 0.001) than in patients with microsatellite stability/MSI-low, RAS/BRAF mutation and RNF43 wildtype, respectively. When these markers were combined, the fusion detection rate increased. Among patients with RAS/BRAF wildtype and MSI-H, fusions were detected in 20.3% of patients. The fusion detection rate further increased to 37.5% when RNF43 mutation was added. The fusion detection rate was also higher in colon cancer than in rectal cancer. No significant differences in clinical or molecular features were found in patients with actionable gene fusions between the Genecast, cBioPortal, and ChimerSeq databases. Conclusions: Approximately 1% of the unselected Chinese CRC population carries actionable gene fusions, mostly involving NTRK. Actionable gene fusions are more prevalent in MSI-H, RAS/BRAF wildtype, or RNF43-mutated CRC, as well as in colon cancer. Mapping of these molecular markers can markedly increase the fusion detection rate, which can help clinicians select candidates for fusion testing and targeted therapy.
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Toosendanin (TSN), a tetracyclic triterpenoid derived from Melia toosendan and M. azedarach, demonstrates broad application prospects in cancer treatment. Although previously employed as a pesticide, recent studies have revealed its potential therapeutic value in treating various types of cancer. TSN exerts an anticancer effect via mechanisms including proliferation inhibition, apoptosis induction, migration suppression, and angiogenesis inhibition. However, TSN's toxicity, particularly its hepatotoxicity, significantly limits its therapeutic application. This review explored the dual nature of TSN, evaluating both its anticancer potential and toxicological risks, emphasizing the importance of balancing these aspects in therapeutic applications. Furthermore, we investigated the incorporation of TSN into novel therapeutic strategies, such as Proteolysis-targeting chimeras (PROTAC) technology and nanotechnology-based drug delivery systems (DDS), which enhance treatment efficacy while mitigating toxicity in normal tissues.
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Medicamentos Herbarios Chinos , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Animales , Apoptosis/efectos de los fármacos , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Sistemas de Liberación de Medicamentos , Proliferación Celular/efectos de los fármacos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , TriterpenosRESUMEN
BACKGROUND: Comprehensive treatment of gastric cancer (GC) is progressing, but the rapid proliferation and metastasis of GC remains a cause of high recurrence and mortality rates. In this study we investigated GC-associated circRNA tending to yield more insight into the mechanisms of gastric cancer development. METHODS: We detected the expression levels of circTSN in GC tissues and cell lines using qRT-PCR. The circular structure of circTSN was confirmed by Sanger sequencing, agarose gel electrophoresis and RNase R. A series of cell functional experiments were employed to investigate the implication of circTSN aberrant expression on the proliferation and metastasis of GC cells. The predicted binding domain between circTSN and miR-1825 was analyzed by luciferase reporter gene analysis. Meanwhile, subcutaneous tumor xenografts in nude mice were used to validate the role of circTSN in vivo. RESULTS: It was found that RNA levels of circTSN were significantly elevated in GC tissues and cell lines, which was also confirmed to contain a closed-loop structure. CCK8, clone formation, EdU, transwell and in vivo experiments indicated that the highly expressed circTSN was involved in the proliferation and metastasis process of GC. In addition, circTSN modulates the expression of SLC38A2 by sequence-specific binding to miR-1825. CONCLUSION: This study identified that circTSN, which is highly expressed in GC, was able to contribute to the proliferation and metastasis of GC cell through miR-1825/SLC38A2 axis and this might provide a new candidate target for the precision treatment of GC.
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The fabrication of scalable all-perovskite tandem solar cells is considered an attractive route to commercialize perovskite photovoltaic modules1. However, The certified efficiency of 1-cm2 scale all-perovskite tandem solar cells lags behind their small-area (~0.1 cm2) counterparts2,3. This performance deficit originates from inhomogeneity in wide-bandgap (WBG) perovskite solar cells (PSCs) at a large scale. The inhomogeneity is known to be introduced at the bottom interface and within the perovskite bulk itself4,5. Here we uncover another crucial source for the inhomogeneity - the top interface formed during the deposition of the electron transport layer (ETL, C60). Meanwhile, the poor ETL interface is also a significant limitation of device performance. We address this issue by introducing a mixture of 4-fluorophenethylamine (F-PEA) and 4-trifluoromethyl-phenylammonium (CF3-PA) to create a tailored two-dimensional perovskite layer (TTDL), in which F-PEA forms a two-dimensional perovskite at the surface reducing contact losses and inhomogeneity, CF3-PA enhances charge extraction and transport. As a result, we demonstrate a high open-circuit voltage of 1.35 V and an efficiency of 20.5% in 1.77-eV WBG PSCs at a square centimeter scale. By stacking with a narrow-bandgap perovskite sub-cell, we report 1.05 cm2 all-perovskite tandem cells delivering 28.5% (certified 28.2%) efficiency, the highest among all reported so far. Our work showcases the importance of treating the top perovskite/ETL contact for upscaling perovskite solar cells.
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The goal of RGB-Thermal (RGB-T) tracking is to utilize the synergistic and complementary strengths of RGB and TIR modalities to enhance tracking in diverse situations, with cross-modal interaction being a crucial element. Earlier methods often simply combine the features of the RGB and TIR search frames, leading to a coarse interaction that also introduced unnecessary background noise. Many other approaches sample candidate boxes from search frames and apply different fusion techniques to individual pairs of RGB and TIR boxes, which confines cross-modal interactions to local areas and results in insufficient context modeling. Additionally, mining video temporal contexts is also under-explored in RGB-T tracking. To alleviate these limitations, we propose a novel Template-Bridged Search region Interaction (TBSI) module that exploits templates as the medium to bridge the cross-modal interaction between RGB and TIR search regions by gathering and distributing target-relevant object and environment contexts. An Illumination Guided Fusion (IGF) module is designed to adaptively fuse RGB and TIR search region tokens with a global illumination factor. Furthermore, in the inference stage, we also propose an efficient Target-Preserved Template Updating (TPTU) strategy, leveraging the temporal context within video sequences to accommodate the target's appearance change. Our proposed modules are integrated into a ViT backbone for joint feature extraction, search-template matching, and cross-modal interaction. Extensive experiments on three popular RGB-T tracking benchmarks demonstrate our method achieves new state-of-the-art performances. Code is available at https://github.com/RyanHTR/TBSI.
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Transcranial direct current stimulation (tDCS) is an important method for treating mental illnesses and neurodegenerative diseases. This paper reconstructed two ex vivo brain slice models based on rat brain slice staining images and magnetic resonance imaging (MRI) data respectively, and the current densities of hippocampus after cortical tDCS were obtained through finite element calculation. Subsequently, a neuron model was used to calculate the response of rat hippocampal pyramidal neuron under these current densities, and the neuronal responses of the two models under different stimulation parameters were compared. The results show that a minimum stimulation voltage of 17 V can excite hippocampal pyramidal neuron in the model based on brain slice staining images, while 24 V is required in the MRI-based model. The results indicate that the model based on brain slice staining images has advantages in precision and electric field propagation simulation, and its results are closer to real measurements, which can provide guidance for the selection of tDCS parameters and scientific basis for precise stimulation.
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Encéfalo , Hipocampo , Imagen por Resonancia Magnética , Estimulación Transcraneal de Corriente Directa , Estimulación Transcraneal de Corriente Directa/métodos , Animales , Ratas , Hipocampo/fisiología , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Simulación por Computador , Células Piramidales/fisiología , Análisis de Elementos Finitos , Modelos Neurológicos , Neuronas/fisiologíaRESUMEN
BACKGROUND: Pet-derived allergens are another source of indoor air pollution which could affect human health. However, the association between pet ownership and the risk of dry eye symptoms (DES) remains to be elucidated. METHODS: We conducted a nationwide cross-sectional survey among Chinese residents aged over 12 years from June 20, 2022 to August 31, 2022. The Ocular Surface Disease Index-6 (OSDI-6) questionnaire was utilized to evaluate the presence of DES. Multivariable logistic regression models were used to analyze the associations between pet ownership and DES. Subgroup analyses were conducted based on sex, age, residence and affective disorders, and sensitivity analysis by excluding participants with major ocular diseases. The interactions between pet ownership and other risk factors on DES were explored in the additive scale by calculating the synergy index (SI). RESULTS: A total of 21,916 subjects replied to the questionnaire. The prevalence of DES was 43.6 % (95 % confidence interval (CI), 43.0 %-44.3 %). Pet ownership was significantly associated with increased risk of DES (Odds ratio (OR): 1.13, 95%CI: 1.05-1.21), especially among the elderly (OR: 1.28, 95%CI: 1.09-1.51) and urban residents (OR: 1.13, 95%CI: 1.04-1.24). The individual effect of allergic rhinitis on DES was 2.59 (95%CI: 1.27-5.53), while the joint effect of pets and allergic rhinitis was 5.26 (95%CI: 1.20-36.74), suggesting a synergistic interaction with a SI of 2.48 (95%CI: 0.25-24.39). Furthermore, the interaction analysis also indicated a synergistic interaction between pet ownership and low health literacy with a SI of 1.12 (95%CI: 0.66-1.87). CONCLUSION: Pet ownership was identified as a risk factor for DES. The synergistic interaction of pet ownership and allergic rhinitis suggests shared mechanisms between DES and allergic conditions.
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Isotschimgine (ITG) is a bornane-type monoterpenoid derivative naturally occurring in genus Ferula plants and propolis. Its effects on aging and the underlying mechanisms are not yet well understood. This study employed Caenorhabditis elegans (C. elegans) as a model organism to evaluate the potential of ITG in extending lifespan, enhancing healthspan, and promoting neuroprotection, while exploring the underlying mechanisms involved. The results showed that ITG extended the lifespan and healthspan of C. elegans, significantly enhanced stress resistance and detoxification functions. Studies on mutants and qPCR data indicated that ITG-mediated lifespan extension was modulated by the insulin/IGF-1 signaling pathway and nuclear hormone receptors. Furthermore, ITG markedly increased stress-responsive genes, including daf-16 and its downstream genes sod-3 and hsp-16.2, as well as NHR downstream detoxification-related genes cyp35a1, cyp35b3, cyp35c1, gst-4, pgp-3 and pgp-13. Additionally, ITG alleviated ß-amyloid-induced paralysis and behavioral dysfunction in transgenic C. elegans strains. The neuroprotective efficacy of ITG was weakened by RNAi knockdown of nuclear hormone receptors daf-12 and nhr-8. Overall, our study identifies ITG as a potential compound for promoting longevity and neuroprotection, mediated through nuclear hormone receptors.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Longevidad , Receptores Citoplasmáticos y Nucleares , Animales , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Longevidad/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Transducción de Señal/efectos de los fármacos , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Envejecimiento/fisiologíaRESUMEN
Six new highly oxidized seco-terpenoids, including three 3-nor-labdane type diterpenes, talaroterpenoids A-C (1-3), and three meroterpenoids containing an orthoester group, talaroterpenoids D-F (6-8), together with five known compounds (4-5 and 9-11), were isolated from the marine-derived fungus Talaromyces aurantiacus. Their chemical structures were elucidated through 1D, 2D NMR, HRESIMS, J-based configuration analysis (JBCA), computational ECD calculations, and single-crystal X-ray diffraction analysis. Compounds 1 and 2 contain an unusual 6,20-γ-lactone-bridged scaffold. Compounds 10 and 11 presented inhibitory effects on NO release in lipopolysaccharide (LPS)-induced BV-2 cells with IC50 values of 11.47 and 11.32 µM, respectively. Talaroterpenoid C (3) showed moderate antifungal activity against A. alternata and P. theae Steyaert.
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Talaromyces , Talaromyces/química , Animales , Terpenos/farmacología , Terpenos/química , Terpenos/aislamiento & purificación , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Ratones , Organismos Acuáticos , Estructura Molecular , Línea Celular , Óxido Nítrico/metabolismo , Cristalografía por Rayos XRESUMEN
Boron (B) is an essential micronutrient for plant growth and development; however, the process of B toxicity in citrus production is still poorly understood. We proposed a hypothesis that B toxicity in citrus trees is related to the characteristics of B transport from soil to leaf or fruit. For this, a field experiment was conducted for two treatments, control (B free or without B) and B fertilizer treatment (100 g Na2B4O7·10H2O plant-1), to investigate the effects on plant growth, nutrient uptake, fruit yield and quality, and B transport in 10-year-old pomelo trees [Citrus grandis (L.) Osbeck cv. Guanximiyou]. Our results showed that excess B fertilization directly led to B toxicity in pomelo trees by dramatically increasing soil total B and water-soluble B contents. B toxicity induced interveinal chlorosis in leaves and decreased leaf biomass and function, resulting in a decreased 45.3% fruit yield by reducing 30.6% fruit load and 21.4% single fruit weight. Also, B toxicity induced changes in mineral elements between leaf positions and fruit parts, in which the concentrations of B, potassium, and magnesium were increased while those of nitrogen and iron were decreased. Under B toxicity conditions, fruit quality parameters of total soluble solids (TSS), TSS/titratable acidity (TA), total soluble sugar, sucrose, pH, vitamin C, and total phenol contents decreased, which were regulated by the lower carbohydrate production in new leaves and the lower transport capacity in old leaves. Moreover, B toxicity significantly increased the transfer factor and bio-concentration factor of B in pomelo plants, with higher levels in leaf organs than in fruit organs. Taken together, excess B fertilization-induced B toxicity in pomelo trees, with induced growth inhibition and nutrient disorder, results in reduced fruit yield and quality, which are related to B transport from soil to organs. The findings of this study highlight the understanding of B toxicity in citrus plants and strengthen B management in pomelo production for high yield and high quality.
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Objective: To explore the distribution and influence factors of non-invasive tear film break-up time (NIBUT) in children. Methods: This is a hospital-based cross-sectional study. Spherical equivalent error (SER) was measured with cycloplegia. NIBUT was measured by an ocular surface integrated analyzer. Results: A total of 1269 children (1269 eyes) were included in this study. Participants' median age was 11 (range 6-18) years. 47.1% (598/1269) of participants were boys. The median NIBUT of myopic children and non-myopic children were 9.9 seconds (s) (Inter-quartile range, IQR: 6.4 to 16.1) and 10.9 s (IQR: 8.8 to 17.9), respectively, which was statistically significant (p = 0.004). In myopic children, 49.9% (573/1148) were able to achieve NIBUT of 10 s or more, compared to 67.8% (82/121) in non-myopic children, which was statistically significant (p < 0.001). There were 41 (3.57%) children in the myopic group and none (0%) in the non-myopic group with dry eye disease (p = 0.028). There was a positive correlation between NIBUT and age: NIBUT = 9.256 + 0.352*Age. 71.8% (824/1148) of myopic children used electronic products almost every day, compared to 37.2% (45/121) of non-myopic children, which was statistically significant (p < 0.001). Conclusion: The NIBUT of myopic children was significantly shorter than that of non-myopic children. Children with myopia are more likely to have dry eyes. NIBUT increases with age. High frequency of electronic product use may be an important cause to NIBUT shortening in children.
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BACKGROUND: Mechanical unloading-induced bone loss threatens prolonged spaceflight and human health. Recent studies have confirmed that osteoporosis is associated with a significant reduction in bone microvessels, but the relationship between them and the underlying mechanism under mechanical unloading are still unclear. METHODS: We established a 2D clinostat and hindlimb-unloaded (HLU) mouse model to simulate unloading in vitro and in vivo. Micro-CT scanning was performed to assess changes in the bone microstructure and mass of the tibia. The levels of CD31, Endomucin (EMCN) and histone deacetylase 6 (HDAC6) in tibial microvessels were detected by immunofluorescence (IF) staining. In addition, we established a coculture system of microvascular endothelial cells (MVECs) and osteoblasts, and qRTâPCR or western blotting was used to detect RNA and protein expression; cell proliferation was detected by CCKâ8 and EdU assays. ChIP was used to detect whether HDAC6 binds to the miRNA promoter region. RESULTS: Bone mass and bone microvessels were simultaneously significantly reduced in HLU mice. Furthermore, MVECs effectively promoted the proliferation and differentiation of osteoblasts under coculture conditions in vitro. Mechanistically, we found that the HDAC6 content was significantly reduced in the bone microvessels of HLU mice and that HDAC6 inhibited the expression of miR-375-3p by reducing histone acetylation in the miR-375 promoter region in MVECs. miR-375-3p was upregulated under unloading and it could inhibit MVEC proliferation by directly targeting low-density lipoprotein-related receptor 5 (LRP5) expression. In addition, silencing HDAC6 promoted the miR-375-3p/LRP5 pathway to suppress MVEC proliferation under mechanical unloading, and regulation of HDAC6/miR-375-3p axis in MVECs could affect osteoblast proliferation under coculture conditions. CONCLUSION: Our study revealed that disuse-induced bone loss may be closely related to a reduction in the number of bone microvessels and that the modulation of MVEC function could improve bone loss induced by unloading. Mechanistically, the HDAC6/miR-375-3p/LRP5 pathway in MVECs might be a promising strategy for the clinical treatment of unloading-induced bone loss.
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Proliferación Celular , Células Endoteliales , Epigénesis Genética , Suspensión Trasera , Histona Desacetilasa 6 , MicroARNs , Microvasos , Osteoblastos , Animales , MicroARNs/metabolismo , MicroARNs/genética , Células Endoteliales/metabolismo , Histona Desacetilasa 6/metabolismo , Histona Desacetilasa 6/genética , Microvasos/patología , Osteoblastos/metabolismo , Ratones Endogámicos C57BL , Ratones , Técnicas de Cocultivo , Diferenciación Celular , Masculino , Resorción Ósea/patología , Secuencia de Bases , Inhibidores de Histona Desacetilasas/farmacologíaRESUMEN
In the university laboratory environment, it is not uncommon for individual laboratory personnel to be inadequately aware of laboratory safety standards and to fail to wear protective equipment (helmets, goggles, masks) in accordance with the prescribed norms. Manual inspection is costly and prone to leakage, and there is an urgent need to develop an efficient and intelligent detection technology. Video surveillance of laboratory protective equipment reveals that these items possess the characteristics of small targets. In light of this, a laboratory protective equipment recognition method based on the improved YOLOv7 algorithm is proposed. The Global Attention Mechanism (GAM) is introduced into the Efficient Layer Aggregation Network (ELAN) structure to construct an ELAN-G module that takes both global and local features into account. The Normalized Gaussian Wasserstein Distance (NWD) metric is introduced to replace the Complete Intersection over Union (CIoU), which improves the network's ability to detect small targets of protective equipment under experimental complex scenarios. In order to evaluate the robustness of the studied algorithm and to address the current lack of personal protective Equipment (PPE) datasets, a laboratory protective equipment dataset was constructed based on multidimensionality for the detection experiments of the algorithm. The experimental results demonstrated that the improved model achieved a mAP value of 84.2 %, representing a 2.3 % improvement compared to the original model, a 5 % improvement in the detection rate, and a 2 % improvement in the Micro-F1 score. In comparison to the prevailing algorithms, the accuracy of the studied algorithm has been markedly enhanced. The approach addresses the challenge of the challenging detection of small targets of protective equipment in complex scenarios in laboratories, and plays a pivotal role in perfecting laboratory safety management system.
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BACKGROUND: The health risk of Se has gained significant attention. Previous studies mainly focused on the health risk of total Se in high-Se area. Less attention has been paid to the health risk of organic selenium in areas with varying selenium levels. METHODS: A total number of 109 crop samples (edible parts) were collected in Langao County, Shannxi Province, China from 2018 to 2020, including 42 corn, 18 rice, 9 sweet potato, 25 potato, 12 radish, and 3 eggplant samples. The hydride generation atomic fluorescence spectrometry (HG-AFS) method was used to determine the total and organic Se contents. RESULT AND CONCLUSION: (1) Corn (2.82â¯mg/kg), rice (0.44â¯mg/kg), potato (6.56â¯mg/kg), and eggplant (0.77â¯mg/kg) in high-Se area, as well as sweet potato (1.07â¯mg/kg) and radish (4.28â¯mg/kg) in medium-Se area, exhibited the highest total Se content among all crops in this county, and 5-328 times higher than the values of Se-enriched standard (2) The average daily intake of total/organic Se of residents in high-Se area reached 676/449⯵g/day, which was 1-4 times higher than levels observed in medium-Se area (419/257⯵g/day) and low-Se area (196/128⯵g/day). The organic Se daily intakes from dietary combinations of rice + radish and rice + eggplant in high-Se area lower than 400⯵g/day, which could be safely consumed. The organic Se daily intakes from dietary combinations of sweet potato + radish and sweet + eggplant in medium-Se area higher than 400⯵g/day, which could not be safely consumed. The total / organic Se daily intakes of all dietary combinations in low-Se area lower than 400⯵g/day, which could be safely consumed. (3) The health risk associated with crops might be overestimated due to the higher non-carcinogenic risk attributed to total Se compared to organic Se. The present study demonstrated that daily intake and health risk of total and organic Se in crops across areas with different Se levels varied significantly.
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The objectives of this research were to analyze anthocyanins in blue honeysuckle (Lonicera caerulea L.), bilberry (Vaccinium vitis-idaea L), and cranberry (Vaccinium macrocarpon Ait.), using HPLC-ESI-QTOF-MS2, Fourteen, fifteen, and eight anthocyanins were identified in blue honeysuckle, bilberry, and cranberry, respectively. Cyanidin-3-glucoside (C3G) and peonidin-3-glucoside were detected in all three types of berries, with blue honeysuckle showing the highest C3G content at 5686.28 mg/100 g DW. Total phenolic content (TPC) and total flavonoid content (TFC), along with ABTS, DPPH, and FRAP assays, were measured. Blue honeysuckle exhibited the highest levels of TPC and TFC. The SOD, POD, and CAT activities in blue honeysuckle were 1761.17 U/g, 45,525.65 U/g, and 1043.24 U/g, respectively, which were significantly superior to those in bilberry and cranberry. The antioxidant mechanisms of these enzymes were investigated by molecular docking, C3G showed a higher affinity for POD, confirming the effectiveness of C3G as an antioxidant.
RESUMEN
Hepatocellular carcinoma (HCC) is a prevalent and lethal malignancy with significant global impact, necessitating the development of novel therapeutic strategies and drugs. Ferroptosis, a newly identified form of iron-dependent programmed cell death, has emerged as a promising strategy to combat HCC. Sappanone A, an isoflavone compound derived from the heartwood of Biancaea sappan (L.) Tod., is known for its anti-inflammatory and antioxidant properties. However, its anti-HCC effects and underlying mechanisms remain unclear. This study is the first time to demonstrate the anti-tumor effect of Sappanone A on HCC both in vitro and in vivo, through the assessment of cell viability and apoptosis following Sappanone A treatment. Flow cytometry and confocal microscopy revealed that Sappanone A induced ferroptosis in HCC cells by increasing Fe2+ accumulation, reactive oxygen (ROS) level, and lipid peroxidation, specifically targeting inosine monophosphate dehydrogenase-2 (IMPDH2). Additionally, Western blot analysis suggested that the anti-HCC effects of Sappanone A were mediated through the regulation of the NRF2/xCT/GPX4 axis, highlighting its potential to enhance ferroptosis in HCC cells and underscoring the critical role of IMPDH2 in HCC treatment.
Asunto(s)
Carcinoma Hepatocelular , Ferroptosis , Isoflavonas , Neoplasias Hepáticas , Factor 2 Relacionado con NF-E2 , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Ferroptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Animales , Isoflavonas/farmacología , Ratones , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Supervivencia Celular/efectos de los fármacos , Masculino , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Lead halide perovskite solar cells (PSCs) have emerged as one of the influential photovoltaic technologies with promising cost-effectiveness. Though with mild processabilities to massive production, inverted PSCs have long suffered from inferior photovoltaic performances due to intractable defective states at boundaries and interfaces. Herein, an in situ passivation (ISP) method is presented to effectively adjust crystal growth kinetics and obtain the well-orientated perovskite films with the passivated boundaries and interfaces, successfully enabled the new access of high-performance inverted PSCs. The study unravels that the strong yet anisotropic ISP additive adsorption between different facets and the accompanied additive engineering yield the high-quality (111)-orientated perovskite crystallites with superior photovoltaic properties. The ISP-derived inverted perovskite solar cells (PSCs) have achieved remarkable power conversion efficiencies (PCEs) of 26.7% (certified as 26.09% at a 5.97 mm2 active area) and 24.5% (certified as 23.53% at a 1.28 cm2 active area), along with decent operational stabilities.