Screening of bacterial endophytes of larch against Neofusicoccum laricinum and validation of their safety.

In order to provide a highly feasible research pathway for the control of larch shoot blight, healthy larch branches and leaves were collected from 13 sampling sites in 8 provinces in China. The antagonistic endophytic bacteria obtained from the screening were used to carry out disease control experiments in potted seedlings. The safety evaluation test was conducted on the antagonistic bacteria. Subsequently, the strains with better preventive effect and high safety were identified by morphological and molecular methods. A total of 391 strains of endophytic bacteria were isolated from healthy larch branches and leaves. Seventy-eight strains of larch endophytic bacteria with antagonistic effect were obtained by primary sieving. Ten strains of endophytic bacteria with obvious antagonism were further obtained by secondary sieving, and all of them had an inhibition rate of more than 57%. Among them, strains YN 2, JL 6, NMG 23, and JL 54 showed the highest inhibition rate of 63.16%-65.08%, which was significantly different from the other treatments. The results of the pot test showed that 14 days after inoculation with the pathogen, strains YN 2 and JL 54 were more effective in the control of larch shoot blight, with the preventive effects reaching 57.7% and 50.0%, respectively. Strains JL 6 and JL 54 were biologically safe in the safety evaluation test. Therefore, strain JL 54 was selected for identification. It was identified as Bacillus amyloliquefaciens through morphological observation, 16S rDNA sequence, gyrB gene sequence and 16S rDNA-gyrB tandem feature sequence analysis. IMPORTANCE: Larch shoot blight is a widely distributed, damaging, and rapidly spreading fungal disease of forest trees that poses a serious threat to larch plantations. Endophytic bacteria have biological effects on host plants against pests and diseases, and they have a growth-promoting effect on plants. In this paper, we investigated for the first time the biocontrol effect of endophytic bacteria on larch shoot blight by screening endophytic bacteria with the function of antagonizing dieback fungi. Bacillus amyloliquefaciens JL 54 has a better prospect of biocontrol against larch shoot blight, which lays the foundation for the application of this bacterium in the future.

Immunosuppressive alkaloids from Narcissus tazetta subsp. Chinensis and the mechanism of (+)-narciclasine in vitro and in vivo.

Three previously undescribed and sixteen known alkaloids were bioguidedly isolated from the bulbs of Narcissus tazetta subsp. chinensis (M.Roem.) Masamura & Yanagih. The structures were elucidated by spectroscopic data, including HRESIMS, NMR, and ECD. Eleven of the isolated alkaloids exhibited immunosuppressive activity on the proliferation of human T cells. (+)-Narciclasine (18) showed the most significantly suppressive activity with an IC50 value of 14 ± 5 nM. In vitro, (+)-narciclasine (18) blocked NF-κB signal transduction, but did not affect PI3K/AKT signal transduction. What was more, (+)-narciclasine significantly reduced ALT and AST levels and alleviated liver damage induced by ConA in AIH mouse model.

Application of immersive virtual reality (IVR) for the care of common diseases of older adults course: A mixed methods study.

OBJECTIVE: This study aimed to enhance understanding, engagement, and learning efficiency in the course "The Care of Common Diseases of Older Adults" using a developed Immersive Virtual Reality(IVR) system. METHODS: A mixed-methods study with 32 students was conducted. The quantitative part involved a randomized controlled trial, and the qualitative part included thematic interviews with students and teachers. RESULTS: The intervention group using the IVR system showed significant improvements in positivity and performance evaluation scores (P < 0.05) compared to the control group. Negative affect scores also decreased significantly (P < 0.05). Qualitative data from interviews supported the quantitative findings, highlighting increased curiosity, learning enthusiasm, and academic performance. CONCLUSION: IVR significantly enhances learning by stimulating curiosity and active participation, making education more accessible and improving student performance. Future IVR enhancements should focus on user-friendliness and empathetic feedback in adult care.

A biomimetic tri-phasic scaffold with spatiotemporal patterns of gastrodin to regulate hierarchical tissue-based vascular regeneration.

Clinical use of small-diameter vascular grafts remains a challenging issue in neovessel regeneration in view of thrombosis and intimal hyperplasia. Developing a vascular graft with structure and function similar to those of the native vessels necessitates a major direction of vascular tissue regeneration. Thus, this study sought to design and fabricate a range of tri-phasic scaffolds (0, 2, and 5 wt% gastrodin-polyurethane (PU)) with spatiotemporally defined structure and gastrodin-release for regulating the highly coordinated processes in growth of the intima and media. While the small pores of inner layer guided infiltration of human umbilical vein endothelial cells (HUVECs), the bigger pores of medial layer could offer smooth muscle cell (SMC)-friendly habitat, and external fibers conferred adequate mechanical properties. Correspondingly, spatial distribution and differential regulation of key proteins in HUVECs and SMCs were mediated by hierarchical release of gastrodin, of which rapid release in inner layer elicited enhanced HUVEC proliferation and migration against those of the SMC via activated endothelial nitric oxide synthase (eNOS) and heat shock protein 70 (HSP70) signal. Of note, superior anti-coagulation was reflected in 2 wt% gastrodin-PU ex vivo extracorporeal blood circulation experiment. After in vivo implantation for 12 weeks, there was no formation of obvious thrombosis and intimal hyperplasia in 2 wt% gastrodin-PU. The scaffold maintained high patency and improved vascular remodeling, including the formation of thin endothelialization in lumen and dense extracellular matrix deposition in medial layer. Taken together, the results demonstrate the positive function of hierarchical releasing system that responded to tri-phasic structure, which not only suppressed intimal thickening but also tightly controlled tissue regeneration.

Aberrant METTL14 gene expression contributes to malignant transformation of benzene-exposed myeloid cells.

Benzene is a known contributor to human leukaemia through its toxic effects on bone marrow cells, and epigenetic modification is believed to be a potential mechanism underlying benzene pathogenesis. However, the specific roles of N6-methyladenosine (m6A), a newly discovered RNA post-transcriptional modification, in benzene-induced hematotoxicity remain unclear. In this study, we identified self-renewing malignant proliferating cells in the bone marrow of benzene-exposed mice through in vivo bone marrow transplantation experiments and Competitive Repopulation Assay. Subsequent analysis using whole transcriptome sequencing and RNA m6A methylation sequencing revealed a significant upregulation of RNA m6A modification levels in the benzene-exposed group. Moreover, RNA methyltransferase METTL14, known as a pivotal player in m6A modification, was found to be aberrantly overexpressed in Lin-Sca-1+c-Kit+ (LSK) cells of benzene-exposed mice. Further analysis based on the GEO database showed a positive correlation between the expression of METTL14, mTOR, and GFI and benzene exposure dose. In vitro cellular experiments, employing experiments such as western blot, q-PCR, m6A RIP, and CLIP, validated the regulatory role of METTL14 on mTOR and GFI1. Mechanistically, continuous damage inflicted by benzene exposure on bone marrow cells led to the overexpression of METTL14 in LSK cells, which, in turn, increased m6A modification on the target genes' (mTOR and GFI1) RNA. This upregulation of target gene expression activated signalling pathways such as mTOR-AKT, ultimately resulting in malignant proliferation of bone marrow cells. In conclusion, this study offers insights into potential early targets for benzene-induced haematologic malignant diseases and provides novel perspectives for more targeted preventive and therapeutic strategies.

Nervogenic Acid Derivatives and Phenanthrenes from Liparis nervosa and Their Antimicrobial and Immunosuppressive Activities.

Two new nervogenic acid derivatives liparisnervosides Q (1) and R (5), as well as five known nervogenic acid derivatives (2-4, 6, 7) and four phenanthrenes (8-11) were isolated from the whole plant of Liparis nervosa (Thunb. ex A. Murray) Lindl.. Their structures were detremined using extensive spectroscopic techniques, including 1D, 2D NMR, and HR-ESI-MS, and acid hydrolysis. Furthermore, their antimicrobial and immunosuppressive activities were evaluated. Nervosine VII (3) exhibited antimicrobial activity against Staphylococcus aureus with an MIC of 62.5 µg/mL and inhibited the proliferation of human T cells with an IC50 value of 9.67±0.96 µM. These findings contribute to our understanding of the potential pharmacological properties of these compounds.

Correlation between different points on the face and the width of maxillary anterior teeth.

Statement of problem: There is currently no consensus on the relationship between maxillary anterior teeth and different facial anthropometric measurements. Additionally, whether these relationships vary by age and sex remains unreported. Purpose: This clinical study aimed to investigate the relationship between the intercanine distance (ICaD) and intercanthal distance (ICD), interpupillary distance (IPD), interalar width (IAW), and intercommissural width (ICW), and to compare whether these relationships differ between different age and sex populations. Material and methods: Participants (n = 409) were enrolled according to the inclusion criteria, and their standardized digital images were taken to measure facial and oral segments through an image processing program. The differences between ICaD and four facial measurements and the sexual differences for all measurements were compared using the 1-sample t-test. The differences among different age groups for all measurements were compared using the one-way analysis of variance (ANOVA) test, and a least significant difference (LSD) test was used for multiple comparisons. The association between ICaD and the four facial measurements was evaluated using Pearson correlation analysis. The correlation between ICaD and four facial measurements was evaluated using linear regression. Differences in regression equations among the subgroups were evaluated through subgroup regression analysis and the significance test of the difference between the two regression coefficients. Tests of significance were two-sided, with alpha level of 0.05. The reliability of the results was evaluated by calculating intraclass correlation coefficients. Results: The ICD, IPD, ICW, and IAW significantly differed from the ICaD in both sexes (P < 0.01). All measurements were significantly greater in men than in women (P < 0.01). The differences among the age groups were statistically significant for all measurements except IPD (P < 0.05). A significant positive correlation was found between all facial measurements (r = 0.258 [ICD], r = 0.334 [IPD], r = 0.389 [ICW], and r = 0.393 [IAW]) and the ICaD in both sexes. The highest correlation was found between ICW(r = 0.345) and ICAD in men and IAW (r = 0.285) and ICAD in women. Except for the 20-29 and 50-59 age groups, the mathematical equations of ICaD and facial anthropometric measurements differed among the other age groups and sexes. Conclusions: ICD, IPD, ICW, and IAW cannot be directly used to determine ICaD in both sexes. Nevertheless, when observed from the frontal aspect, by the use of digital images, all facial measurements correlated to the intercanine distance, with a high probability. The mathematical formulae combined with facial anthropological measurements can help ensure the combined width of the six maxillary anterior teeth, but the effects of sex and age differences should be considered.

In Situ Synthesis of Gold Nanoparticles from Chitin Nanogels and Their Drug Release Response to Stimulation.

In this study, gold nanoparticles (AuNPs) were synthesized in situ using chitin nanogels (CNGs) as templates to prepare composites (CNGs@AuNPs) with good photothermal properties, wherein their drug release properties in response to stimulation by near-infrared (NIR) light were investigated. AuNPs with particle sizes ranging from 2.5 nm to 90 nm were prepared by varying the reaction temperature and chloroauric acid concentration. The photothermal effect of different materials was probed by near-infrared light. Under 1 mg/mL of chloroauric acid at 120 °C, the prepared CNGs@AuNPs could increase the temperature by 32 °C within 10 min at a power of 2 W/cm2. The Adriamycin hydrochloride (DOX) was loaded into the CNGs@AuNPs to investigate their release behaviors under different pH values, temperatures, and near-infrared light stimulations. The results showed that CNGs@AuNPs were pH- and temperature-responsive, suggesting that low pH and high temperature could promote drug release. In addition, NIR light stimulation accelerated the drug release. Cellular experiments confirmed the synergistic effect of DOX-loaded CNGs@AuNPs on chemotherapy and photothermal therapy under NIR radiation.

PROTACs Targeting BRM (SMARCA2) Afford Selective In Vivo Degradation over BRG1 (SMARCA4) and Are Active in BRG1 Mutant Xenograft Tumor Models.

The identification of VHL-binding proteolysis targeting chimeras (PROTACs) that potently degrade the BRM protein (also known as SMARCA2) in SW1573 cell-based experiments is described. These molecules exhibit between 10- and 100-fold degradation selectivity for BRM over the closely related paralog protein BRG1 (SMARCA4). They also selectively impair the proliferation of the H1944 "BRG1-mutant" NSCLC cell line, which lacks functional BRG1 protein and is thus highly dependent on BRM for growth, relative to the wild-type Calu6 line. In vivo experiments performed with a subset of compounds identified PROTACs that potently and selectively degraded BRM in the Calu6 and/or the HCC2302 BRG1 mutant NSCLC xenograft models and also afforded antitumor efficacy in the latter system. Subsequent PK/PD analysis established a need to achieve strong BRM degradation (>95%) in order to trigger meaningful antitumor activity in vivo. Intratumor quantitation of mRNA associated with two genes whose transcription was controlled by BRM (PLAU and KRT80) also supported this conclusion.

Assessing the impact of pine wilt disease on aboveground carbon storage in planted Pinus massoniana Lamb. forests via remote sensing.

The continuous spread of Bursaphelenchus xylophilus (Steiner and Buhrer) Nickle, commonly known as the organism that causes pine wilt disease (PWD), has become a notable threat to forest security in East Asia and southern Europe, and an assessment of the carbon loss caused by PWD damage is important to achieving carbon neutrality. This study used satellite remote sensing and 15-year ground monitoring data to measure the impact of PWD on the carbon storage of Pinus massoniana Lamb. (P. massoniana), the conifer with the largest planted area in southern China. This study showed that the occurrence of PWD had an impact on the increase in carbon storage of P. massoniana. The infected and dead P. massoniana trees accounted for only 1.46 % of the total number of trees but caused a carbon storage loss of 1.99 t/ha, which accounted for 6.23 % of the total carbon sink in healthy P. massoniana forests over the last 15 years. The most pronounced decline in carbon storage occurred in the first five years of PWD invasion. After 10 years of clearcutting and replanting of Schima superba Gardn. et Champ., the increase in carbon storage of the reformed forest far exceeded that of the healthy forest during the same period, which was 2.04 times (10 years) and 1.56 times (15 years) that of the healthy P. massoniana forest. In addition, our study found that during the 15-year period (from the forest age of 22 to the forest age of 37), the average carbon storage of P. massoniana forest was 31.9 t/ha. This study helps to evaluate the impact of PWD on the carbon sink of pine forests and provides methodological references for analyzing the impact of biological disturbances on the carbon cycle.

Effects of AMF inoculation on the growth, photosynthesis and root physiological morphology of root-pruned Robinia pseudoacacia seedlings.

Root pruning hinders the absorption and utilization of nutrients and water by seedlings in the short term. Arbuscular mycorrhizal fungi (AMF) are an important source of nutrient and water for seedlings except for the root system. However, the mechanism by which AMF affect the physiological growth of seedlings after root pruning has rarely been studied. In this study, a pot experiment was conducted through a three-compartment partition system to clarify the effects of Funneliformis mosseae (F. mosseae) strain BGC XJ07A on the physiological growth of root-pruned Robinia pseudoacacia seedlings. Five root pruning treatments (zero, one-fifth, one-fourth, one-third and one-half of the taproot length were removed) were applied to noninoculated seedlings and those inoculated with F. mosseae. The results showed that the presence of F. mosseae significantly increased the shoot and root biomasses, leaf photosynthetic rate, stomatal conductance and transpiration rate. The root projected area, root surface area, average root diameter, root density, root volume and number of root tips of the inoculated seedlings were higher than those without inoculation in all root pruning treatments. The root cytokinin, gibberellins and indole-3-acetic acid concentrations, but root abscisic acid concentration, were higher than those measured in the absence of inoculation in all root pruning treatments. Moreover, the changes in the root endogenous hormone concentrations of the seedlings were closely related to the root morphological development and seedling biomass. The AMF increased the soil available nitrogen, soil available phosphorus, soil available potassium and soil organic matter concentrations compared with the noninoculated treatment. These results indicate that AMF can alleviate the adverse effects of root pruning on the physiological growth of R. pseudoacacia and soil properties, and can provide a basis for AMF application to forest cultivation and the sustainable development of forest ecosystems.

A novel and independent survival prognostic model for OSCC: the functions and prognostic values of RNA-binding proteins.

BACKGROUND: Oral squamous cell carcinoma (OSCC), exhibiting high morbidity and malignancy, is the most common type of oral cancer. The abnormal expression of RNA-binding proteins (RBPs) plays important roles in the occurrence and progression of cancer. The objective of the present study was to establish a prognostic assessment model of RBPs and to evaluate the prognosis of OSCC patients. METHODS: Gene expression data in The Cancer Genome Atlas (TCGA) were analyzed by univariate Cox regression analysis model that established a novel nine RBPs, which were used to build a prognostic risk model. A multivariate Cox proportional regression model and the survival analysis were used to evaluate the prognostic risk model. Moreover, the receive operator curve (ROC) analysis was tested further the efficiency of prognostic risk model based on data from TCGA database and Gene Expression Omnibus (GEO). RESULTS: Nine RBPs' signatures (ACO1, G3BP1, NMD3, RNGTT, ZNF385A, SARS, CARS2, YARS and SMAD6) with prognostic value were identified in OSCC patients. Subsequently, the patients were further categorized into high-risk group and low-risk in the overall survival (OS) and disease-free survival (DFS), and external validation dataset. ROC analysis was significant for both the TCGA and GEO. Moreover, GSEA revealed that patients in the high-risk group significantly enriched in many critical pathways correlated with tumorigenesis than the low, including cell cycle, adheres junctions, oocyte meiosis, spliceosome, ERBB signaling pathway and ubiquitin-mediated proteolysis. CONCLUSIONS: Collectively, we developed and validated a novel robust nine RBPs for OSCC prognosis prediction. The nine RBPs could serve as an independent and reliable prognostic biomarker and guiding clinical therapy for OSCC patients.

Liquid chromatography-mass spectrometry-based metabolomics and fluxomics reveals the metabolic alterations in glioma U87MG multicellular tumor spheroids versus two-dimensional cell cultures.

RATIONALE: Multicellular tumor spheroids (MCTSs) that reconstitute the metabolic characteristics of in vivo tumor tissue may facilitate the discovery of molecular biomarkers and effective anticancer therapies. However, little is known about how cancer cells adapt their metabolic changes in complex three-dimensional (3D) microenvironments. Here, using the two-dimensional (2D) cell model as control, the metabolic phenotypes of glioma U87MG multicellular tumor spheroids were systematically investigated based on static metabolomics and dynamic fluxomics analysis. METHODS: A liquid chromatography-mass spectrometry-based global metabolomics and lipidomics approach was adopted to survey the cellular samples from 2D and 3D culture systems, revealing marked molecular differences between them. Then, by means of metabolomic pathway analysis, the metabolic pathways altered in glioma MCTSs were found using 13 C6 -glucose as a tracer to map the metabolic flux of glycolysis, the tricarboxylic acid (TCA) cycle, de novo nucleotide synthesis, and de novo lipid biosynthesis in the MCTS model. RESULTS: We found nine metabolic pathways as well as glycerolipid, glycerophospholipid and sphingolipid metabolism to be predominantly altered in glioma MCTSs. The reduced nucleotide metabolism, amino acid metabolism and glutathione metabolism indicated an overall lower cellular activity in MCTSs. Through dynamic fluxomics analysis in the MCTS model, we found that cells cultured in MCTSs exhibited increased glycolysis activity and de novo lipid biosynthesis activity, and decreased the TCA cycle and de novo purine nucleotide biosynthesis activity. CONCLUSIONS: Our study highlights specific, altered biochemical pathways in MCTSs, emphasizing dysregulation of energy metabolism and lipid metabolism, and offering novel insight into metabolic events in glioma MCTSs.

Lipid metabolism reprogramming in head and neck cancer.

Lipid metabolism reprogramming is one of the most prominent metabolic anomalies in cancer, wherein cancer cells undergo dysregulation of lipid metabolism to acquire adequate energy, cell membrane building blocks, as well as signaling molecules essential for cell proliferation, survival, invasion, and metastasis. These adaptations enable cancer cells to effectively respond to challenges posed by the tumor microenvironment, leading to cancer therapy resistance and poor cancer prognosis. Head and neck cancer, ranking as the seventh most prevalent cancer, exhibits numerous abnormalities in lipid metabolism. Nevertheless, the precise role of lipid metabolic rewiring in head and neck cancer remains unclear. In line with the LIPID MAPS Lipid Classification System and cancer risk factors, the present review delves into the dysregulated molecules and pathways participating in the process of lipid uptake, biosynthesis, transportation, and catabolism. We also present an overview of the latest advancements in understanding alterations in lipid metabolism and how they intersect with the carcinogenesis, development, treatment, and prognosis of head and neck cancer. By shedding light on the significance of metabolic therapy, we aspire to improve the overall prognosis and treatment outcomes of head and neck cancer patients.

Burden of female infertility in China from 1990 to 2019: a temporal trend analysis and forecasting, and comparison with the global level.

BACKGROUND: Infertility is a common reproductive disease that affects not only individuals and families, but also the growth of the social population. Hence, understanding the burden of female infertility in China and worldwide is of great significance for the development of infertility prevention and treatment strategies. METHODS: The Global Burden of Disease Study (GBD 2019) Data Resources were used to collect and collate relevant data on female infertility in China and worldwide from 1990 to 2019. The difference in the number, age-standardised prevalence rate (ASPR), disability-adjusted life years and age-standardised disability-adjusted life years rate (ASDR) of women with infertility in different periods and geographical areas were analysed. The autoregressive integrated moving average method was used to predict the ASPR and ASDR of female infertility in China and worldwide in the next 11years. RESULTS: In the past 30years, the number of female infertility cases increased by 7.06million in China and 56.71million worldwide. The corresponding average annual increase of ASPR was 10.10% and 7.28%, respectively, and that of ASDR was 0.08% and 0.79%, respectively. In addition, there are differences in age and time between Chinese and global female infertility. In 1990, the crude prevalence rate of female infertility was the highest in women aged 40-44years and 35-39years in China and worldwide, respectively. In 2019, the crude prevalence rate of female infertility was still the highest in women aged 40-44years in China, whereas that around the world reached the highest in women aged 30-34years, which was significantly earlier. The forecast for the next 11years suggests that the ASPR and ASDR for female infertility in China will first rise and then decline, but the overall magnitude of change is not very significant, whereas the ASPR and ASDR for female infertility globally are still on the rise. The ASPR value of female infertility is expected to be 5025.56 in 100 000 persons in China and 3725.51 in 100 000 persons worldwide by 2030. The ASDR value of female infertility is expected to be 26.16 in 100 000 persons in China and 19.96 in 100 000 persons worldwide by 2030. CONCLUSION: The burden of female infertility is still increasing in China and worldwide. Therefore, it is of great significance to pay more attention to infertile women, and advocate a healthy lifestyle to reduce the burden of disease for infertile women.

The role of the thyroid in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disease in women of childbearing age and can cause metabolic disorder, infertility, and increased anxiety and depression; as a result, it can seriously affect the physical and mental health of fertile women. PCOS is a highly clinically heterogeneous disease with unclear etiology and pathogenesis, which increases the difficulty of treatment. The thyroid gland has complex regulatory effects on metabolism, reproduction, and emotion, and produces hormones that act on almost all cells of the human body. The clinical manifestations of PCOS are similar to some thyroid diseases. Furthermore, some thyroid diseases, such as subclinical hypothyroidism (SCH), not only increase the incidence rate of PCOS, but also exacerbate its associated metabolic abnormalities and reproductive disorders. Interestingly, PCOS also increases the incidence of some thyroid diseases. However, the role of the thyroid in PCOS remains unclear. This review is intended to thoroughly explore the critical role of the thyroid in PCOS by summarizing the comorbidity of PCOS and thyroid diseases and their combined role in metabolic disorders, related metabolic diseases, and reproductive disorders; and by analyzing the potential mechanism through which the thyroid influences the development and progression of PCOS and its symptoms. We hope this review will provide a valuable reference for the role of the thyroid in PCOS.

Effect of B/Si molar ratio on the structure and properties of borosilicate bioactive glasses assessed using molecular dynamics simulations.

Due to the improvement and innovation of theoretical methods and the increasing enhancement of high performance computing, computer simulations provide a new method and strategy for optimizing complex composition of novel bioactive glass. In this work, molecular dynamics simulations were used to analyze the effect of B/Si molar ratio on the structure of borosilicate bioactive glass (BBG) and to investigate the effect of structural alterations on its ions release and biological effects. Structural descriptor a theoretical structural descriptor that estimates the overall strength of the glass network (Fnet) was calculated from the simulated data, and the linear relationships ofFnetwith B and Mg releasing rate in deionized water and simulated body fluid were built.In vitromineralization experiments showed that all three BBGs could generate hydroxyapatite and the release of some network modifier ions such as Mg would be regulated by the B/Si ratio.In vitrocellular experiments revealed that the BBG sample with a composition of 1.25B (6Na2O-8K2O-8MgO-22CaO-22.5B2O3-2P2O5-31.5SiO2) promoted the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells, and significantly enhanced the expression of osteogenesis-related genes such as osteopontin, which might be related to the release of Mg at an early stage.

Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids.

Three-dimensional (3D) cell spheroid models combined with mass spectrometry imaging (MSI) enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions. Herein, airflow-assisted desorption electrospray ionization-MSI (AFADESI-MSI) was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone (AMI). High-coverage imaging of >1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI. Following AMI treatment at different times, 15 metabolites of AMI involved in N-desethylation, hydroxylation, deiodination, and desaturation metabolic reactions were identified, and according to their spatiotemporal dynamics features, the metabolic pathways of AMI were proposed. Subsequently, the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis. The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism, providing considerable evidence for the mechanism of AMI hepatotoxicity. In addition, a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI. The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal information for drugs, drug metabolites, and endogenous metabolites after AMI treatment, providing an effective tool for in vitro drug hepatotoxicity evaluation.