Synergetic effects and inhibition mechanisms of the polysaccharide-selenium nanoparticle complex in human hepatocarcinoma cell proliferation.

BACKGROUND: Active components from natural fungal products have shown promising potential as anti-tumor therapeutic agents. In the search for anti-tumor agents, research to overcome the drawbacks of high molecular weight and low bioavailability of pure polysaccharides, polysaccharide-conjugated selenium nanoparticles (SeNPs) has attracted much attention. RESULTS: A novel polysaccharide-selenium nanoparticle complex was produced, in which SeNPs were decorated with polysaccharide obtained from fermented mycelia broth of Lactarius deliciosus (FLDP). Transmission electron microscope, dynamic light scattering, and X-ray photoelectron spectroscopy were utilized to characterize the FLDP-SeNPs; and human hepatocarcinoma cell line (HepG2) was used to assess growth inhibition efficacy. The FLDP-SeNPs that were prepared had a spherical shape with the smallest mean diameter of 32 nm. The FLDP-SeNPs showed satisfactory dispersibility and stability after combination, demonstrating that a reliable consolidated structure had formed. The results revealed that FLDP-SeNPs had notable growth inhibition effects on HepG2 cells. They reduced the membrane potential of mitochondria significantly, increased the generation of reactive oxygen species, enhanced levels of both Caspase-3 and Caspase-9, and led to the nucleus in a wrinkled form. CONCLUSION: The FLDP-SeNPs could exert a synergetic toxicity reduction and inhibition enhancement effect on HepG2 cells by inducing early apoptosis, through mitochondria-mediated cytochrome C-Caspases and reactive oxygen species-induced DNA damage pathways. These results indicate that FLDP-SeNP treatment of HepG2 cells induced early apoptosis with synergetic efficacy, showing that FLDP-SeNPs can be useful as natural anti-tumor agents. © 2024 Society of Chemical Industry.

Management of Triplet States in Modified Mononuclear Ruthenium(II) Complexes for Enhanced Photocatalysis.

Controlling the interplay between relaxation and charge/energy transfer processes in the excited states of photocatalysts is crucial for the performance of artificial photosynthesis. Metal-to-ligand charge-transfer triplet states (3MLCT*) of ruthenium(II) complexes are broadly implemented for photocatalysis, but an effective means of managing the triplets for enhanced photocatalysis has been lacking. Herein, We proposed a strategy to considerably prolong the triplet excited-state lifetime by decorating a ruthenium(II) phosphine complex (RuP-1) with pendent polyaromatic hydrocarbons (PAHs). Systematic studies demonstrate that in RuP-4 decorated with anthracene, sub-picosecond electron transfer from anthracene to 3MLCT* leads to a charge-separated state that can mediate the formation of the intra-ligand triplet state (3IL) of anthracene, resulting in an exceptionally long excited-state up to several milliseconds. This triplet management strategy enables impressive photocatalytic reduction of CO2 to CO with a turnover number (TON) of 404, an optimized quantum yield of 43 % and 100 % selectivity, which is the highest reported performance for mononuclear photocatalysts without additional photosensitizers. RuP-4 also catalyzes photochemical hydrogen generation under argon. This work opens up an avenue for regulating the excited-state charge/energy flow for the development of long-lived 3IL multi-functional mononuclear photocatalysts to boost artificial photosynthesis.

The association between physical activity intensity and frailty risk among older adults across different age groups and genders: Evidence from four waves of the China Health and Retirement Longitudinal Survey.

"Exercise is the best medicine" is well known, but the optimal dose of physical activity (PA) for males and females across different age groups is still unknown. This study, using data from the four waves of CHARLS, aimed to determine the optimal PA dose that reduces frailty risks among older adults across various age groups and both sexes. We created a frailty index score using 63 health-related variables and used 0.21 as the frailty cut point. Binary logistic regression was used to compare the effect of vigorous, moderate, and light intensity PA under IPAQ criteria on frailty risk. The study found that regardless of whether males or females, the optimal effect of vigorous-intensity PA in reducing the risk of frailty is consistently observed throughout the entire old age career. Moreover, the age groups at which moderate-intensity PA reduces the risk of frailty were from age 70 for males and from age 80 for females. And light-intensity PA had no effect on reducing the risk of frailty. Moderate and vigorous intensity of PA in older adults should be promoted, but guidelines and recommendations must account for optimal associations with PA dose across genders and age groups.

Detection of dental caries in oral photographs taken by mobile phones based on the YOLOv3 algorithm.

BACKGROUND: The aim of this study was to explore the value of using the YOLOv3 algorithm for detection and diagnosis of dental caries in oral photographs taken with mobile phones. METHODS: Oral photographs taken with the mobile phones of 570 patients were used as 3 datasets: the augmented images (n=3,990), the enhanced images (n=3,990), and the combined augmented and enhanced images (n=7,980). Oral photographs taken by mobile phones from another 70 patients were used as an independent test set. We used the YOLOv3 network for migration learning for modelling. Diagnostic precision, recall, F1-score, and mean average precision (mAP) were calculated to obtain the detection and diagnostic performance of the YOLOv3 algorithm. RESULTS: After 3 independent training, the mAP value of the original group YOLOv3 algorithm was 56.20%, in which the precision for primary caries recognition was 76.92%, recall was 49.59%, and F1-score was 0.60; the precision for secondary caries recognition was 91.67%, recall was 52.38%, and F1-score was 0.67. The mAP value of the enhance group algorithm was 66.69%, in which the precision for primary caries identification was 81.82%, recall was 52.07%, and F1-score was 0.64, and the precision for secondary caries identification was 100%, recall was 33.33%, and F1-score was 0.50. The mAP value of the comprehensive group algorithm was 85.48%, in which the precision for primary caries identification was 93.33%, recall was 69.42%, F1-score was 0.80, and the F1-score for secondary caries identification was 0.50; precision was 100%, recall was 52.38%, and F1-score was 0.69. CONCLUSIONS: The caries detection capability based on the YOLOv3 algorithm highlights the potential utility of deep learning in caries detection and diagnosis. Comparing the 3 experiments, the detection of the model trained after using image augmented and enhancement techniques was significantly improved.

Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model.

BACKGROUND: The healing of bone defects can be challenging for clinicians to manage, especially after exposure to ionizing radiation. In this regard, radiation therapy and accidental exposure to gamma (γ)-ray radiation have been shown to inhibit bone formation and increase the risk of fractures. Cortical bone-derived stem cells (CBSCs) are reportedly essential for osteogenic lineages, bone maintenance and repair. This study aimed to investigate the effects of melatonin on postradiation CBSCs and bone defect healing. METHODS: CBSCs were extracted from C57BL/6 mice and were identified by flow cytometry. Then CBSCs were subjected to 6 Gy γ-ray radiation followed by treatment with various concentrations of melatonin. The effects of exogenous melatonin on the self-renewal and osteogenic capacity of postradiation CBSCs in vitro were analyzed. The underlying mechanisms involved in genomic stability, apoptosis and oxidative stress-related signaling were further analyzed by Western blotting, flow cytometry and immunofluorescence assays. Moreover, postradiation femoral defect models were established and treated with Matrigel and melatonin. The effects of melatonin on postradiation bone healing in vivo were evaluated by micro-CT and pathological analysis. RESULTS: The decrease in radiation-induced self-renewal and osteogenic capacity were partially reversed in postradiation CBSCs treated with melatonin (P < 0.05). Melatonin maintained genomic stability, reduced postradiation CBSC apoptosis and intracellular oxidative stress, and enhanced expression of antioxidant-related enzymes (P < 0.05). Western blotting validated the anti-inflammatory effects of melatonin by downregulating interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels via the extracellular regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway. Melatonin was also found to exhibit antioxidant effects via NRF2 signaling. In vivo experiments demonstrated that the newly formed bone in the melatonin plus Matrigel group had higher trabecular bone volume per tissue volume (BV/TV) and bone mineral density values with lower IL-6 and TNF-α levels than in the irradiation and the Matrigel groups (P < 0.05). CONCLUSION: This study suggested that melatonin could protect CBSCs against γ-ray radiation and assist in the healing of postradiation bone defects.

Downregulated brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 inhibits osteogenesis of BMSCs through p53 in type 2 diabetes mellitus.

The bone marrow mesenchymal stem cells (BMSCs)-mediated abnormal bone metabolism can delay and impair the bone remodeling process in type 2 diabetes mellitus (T2DM). Our previous study demonstrated that the downregulation of brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1), a circadian clock protein, inhibited the Wnt/ß-catenin pathway via enhanced GSK-3ß in diabetic BMSCs. In this article, we confirmed that the downregulated BMAL1 in T2DM played an inhibitory role in osteogenic differentiation of BMSCs. Upregulation of BMAL1 in the diabetic BMSCs significantly recovered the expression pattern of osteogenic marker genes and alkaline phosphatase (Alp) activity. We also observed an activation of the p53 signaling pathways, exhibited by increased p53 and p21 in diabetic BMSCs. Downregulation of p53 resulting from overexpression of BMAL1 was detected, and when we applied p53 gene silencing (shRNA) and the p53 inhibitor, pifithrin-α (PFT-α), the impaired osteogenic differentiation ability of diabetic BMSCs was greatly restored. However, there was no change in the level of expression of BMAL1. Taken together, our results first revealed that BMAL1 regulated osteogenesis of BMSCs through p53 in T2DM, providing a novel direction for further exploration of the mechanism underlying osteoporosis in diabetes.