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BackgroundAmeloblastoma is a locally invasive and aggressive epithelial odontogenic neoplasm. The BRAF-V600E gene mutation is a prevalent genetic alteration found in this tumor and is considered to have a crucial role in its pathogenesis. The objective of this study is to develop and validate a radiomics-based machine learning method for the identification of BRAF-V600E gene mutations in ameloblastoma patients.MethodsIn this retrospective study, data from 103 patients diagnosed with ameloblastoma who underwent BRAF-V600E mutation testing were collected. Of these patients, 72 were included in the training cohort, while 31 were included in the validation cohort. To address class imbalance, synthetic minority over-sampling technique (SMOTE) is applied in our study. Radiomics features were extracted from preprocessed CT images, and the most relevant features, including both radiomics and clinical data, were selected for analysis. Machine learning methods were utilized to construct models. The performance of these models in distinguishing between patients with and without BRAF-V600E gene mutations was evaluated using the receiver operating characteristic (ROC) curve.ResultsWhen the analysis was based on radiomics signature, Random Forest performed better than the others, with the area under the ROC curve (AUC) of 0.87 (95%CI, 0.68-1.00). The performance of XGBoost model is slightly lower than that of Random Forest, and its AUC is 0.83 (95% CI, 0.60-1.00). The nomogram evident that among younger women, the affected region primarily lies within the mandible, and patients with larger tumor diameters exhibit a heightened risk. Additionally, patients with higher radiomics signature scores are more susceptible to the BRAF-V600E gene mutations.ConclusionsOur study presents a comprehensive radiomics-based machine learning model using five different methods to accurately detect BRAF-V600E gene mutations in patients diagnosed with ameloblastoma. The Random Forest model’s high predictive performance, with AUC of 0.87, demonstrates its potential for facilitating a convenient and cost-effective way of identifying patients with the mutation without the need for invasive tumor sampling for molecular testing. This non-invasive approach has the potential to guide preoperative or postoperative drug treatment for affected individuals, thereby improving outcomes.

Understanding the functions of enzymes in various physiological processes is important, but the design of signaling probes for fast analysis of enzymatic activity is particularly challenging. Herein, a fluorescence-enhanced probe, 10-methyl-2-nitro-acridone (MNA), was synthesized and applied to analyze nitroreductase (NTR) activity in vitro and in vivo. The detection mechanism is based on the nitro group in MNA reacting toward NTR with high reactivity and generating 10-methyl-2-amino- acridone (MAA) accompanied by an obvious fluorescence signal enhancement at 525 nm emission. The probe shows low cytotoxicity, fast response, and high selectivity and sensitivity with a limit of detection as low as 150 ng·mL−1. The probe was also employed for two-photon fluorescence imaging of NTR in zebrafish in vivo revealing the distribution of NTR. Versus existing NTR probes, the proposed probe shows favorable analytical performance including near-infrared light excitation with no other byproducts produced after the reaction. The superior properties of this signaling probe allow it to become a fluorescence imaging candidate in other biosystems.

AimTo determine the effect of safranal on diabetic retinopathy in vitro and its possible mechanisms.MethodsWe used human retinal microvascular endothelial cells (HRMECs) to test the influence of safranal in vitro. High glucose damage was established and an safranal was tested at various concentrations for its potential to reduce cell viability using the MTT assay. We also employed apoptosis detection, cell cycle detection, a transwell test, and a tube formation assay to look into safranal’s inhibitory effects on high glucose damage at various doses. Furthermore, mRNA transcriptome sequencing was performed. mRNA expression levels in a high glucose damage model, a high glucose damage model treated with safranal, and a blank control were compared to find the possible signaling pathway. Western blotting was used to confirm the expressions of several molecules and the levels of phosphorylation in each for the newly discovered pathway.ResultsCell proliferation was inhibited under a high glucose condition but could be protected by safranal at different concentrations (P

The peel and fruit of Citrus varieties have been a raw material for some traditional Chinese medicine (TCM). Pure total flavonoids from Citrus maxima (Burm.) Merr. (PTFC), including naringin, hesperidin, narirutin, and neohesperidin, have been attracted increasing attention for their multiple clinical efficacies. Based on existing in vitro and in vivo research, this study systematically reviewed the biological functions of PTFC and its components in preventing or treating liver metabolic diseases, cardiovascular diseases, intestinal barrier dysfunction, as well as malignancies. PTFC and its components are capable of regulating glycolipid metabolism, blocking peroxidation and persistent inflammation, inhibiting tumor progression, protecting the integrity of intestinal barrier and positively regulating intestinal microbiota, while the differences in fruit cultivation system, picking standard, manufacturing methods, delivery system and individual intestinal microecology will have impact on the specific therapeutic effect. Thus, PTFC is a promising drug for the treatment of some chronic diseases, as well as continuous elaborate investigations are necessary to improve its effectiveness and bioavailability.

Aims: We aimed to assess the impact of extracorporeal membrane oxygenation (ECMO) on voriconazole exposure.Methods: Adult critically ill patients with or without ECMO support receiving intravenous voriconazole therapy were included in this retrospective study conducted in a tertiary referral intensive care unit. The first therapeutic drug monitoring (TDM) results of voriconazole in ECMO patients and non-ECMO patients were collected, and the prevalence of subtherapeutic concentrations was analyzed. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure.Results: A total of 132 patients (including 66 patients with ECMO support) were enrolled and their respective first voriconazole trough concentrations (Cmin) were recorded. The median Cmin of the ECMO group and the non-ECMO group was 1.9 (1.4–4.4) and 4.4 (3.2–6.9) mg/L, respectively (p = 0.000), and the proportion of the two groups in subtherapeutic concentrations range (

ObjectiveChemotherapy-related brain impairments and changes can occur in patients with lung cancer after platinum chemotherapy and have a substantial impact on survivors’ quality of life. Therefore, it is necessary to understand the brain neuropathological alterations and response mechanisms to provide a theoretical basis for rehabilitation strategies. This study aimed to investigate the related brain morphological changes and clarified their correlation with clinical and pathological indicators in patients with lung cancer after platinum chemotherapy.MethodsOverall, 28 patients with chemotherapy, 56 patients without chemotherapy, and 41 healthy controls were categorized in three groups, matched for age, sex, and years of education, and included in the cross-sectional comparison of brain volume and cortical thickness. 14 matched patients before and after chemotherapy were subjected to paired comparison for longitudinal observation of brain morphological changes. Three-dimensional T1-weighted images were acquired from all participants, and quantitative parameters were calculated using the formula of the change from baseline. Correlation analysis was performed to evaluate the relationship between abnormal morphological indices and clinical information of patients.ResultsBrain regions with volume differences among the three groups were mainly distributed in frontal lobe and limbic cortex. Additionally, significant differences in cerebrospinal fluid were observed in most ventricles, and the main brain regions with cortical thickness differences were the gyrus rectus and medial frontal cortex of the frontal lobe, transverse temporal gyrus of the temporal lobe, insular cortex, anterior insula, and posterior insula of the insular cortex. According to the paired comparison, decreased brain volumes in the patients after chemotherapy appeared in some regions of the frontal, parietal, temporal, and occipital lobes; limbic cortex; insular cortex; and lobules VI-X and decreased cortical thickness in the patients after chemotherapy was found in the frontal, temporal, limbic, and insular cortexes. In the correlation analysis, only the differentiation degree of the tumor and duration after chemotherapy were significantly correlated with imaging indices in the abnormal brain regions.ConclusionsOur findings illustrate the platinum-related brain reactivity morphological alterations which provide more insights into the neuropathological mechanisms of patients with lung cancer after platinum chemotherapy and empirical support for the details of brain injury related to cancer and chemotherapy.

Physiological root resorption of deciduous teeth is a normal phenomenon. How the angiogenesis process is regulated to provide adequate levels of oxygen and nutrients in hypoxic conditions when the dental pulp tissue is reduced at the stage of root resorption is not fully understood. In this study, we designed hypoxic preconditioning (2%) to mimic the physiological conditions. We isolated exosomes from hypoxic-preconditioned SHED (Hypo-exos) cells and from normally cultured SHED cells (Norm-exos). We found that treatment with Hypo-exos significantly enhanced the growth, migration and tube formation of endothelial cells in vitro compared with Norm-exos. We also performed matrigel plug assays in vivo and higher expression of VEGF and higher number of lumenal structures that stained positive for CD31 were found in the Hypo-exos treated group. To understand the potential molecular mechanism responsible for the positive effects of Hypo-exos, we performed exosomal miRNA sequencing and validated that Hypo-exos transferred both let-7f-5p and miR-210-3p to promote the tube formation of endothelial cells. Further study revealed that those two miRNAs regulate angiogenesis via the let-7f-5p/AGO1/VEGF and/or miR-210-3p/ephrinA3 signal pathways. Finally, we found that the increased release of exosomes regulated by hypoxia treatment may be related to Rab27a. Taking these data together, the present study demonstrates that exosomes derived from hypoxic-preconditioned SHED cells promote angiogenesis by transferring let-7f-5p and miR-210-3p, which suggests that they can potentially be developed as a novel therapeutic approach for pro-angiogenic therapy in tissue regeneration engineering.

Purpose: To investigate the dynamic functional connectivity (DFC) and static parameters of graph theory in individuals with subjective cognitive decline (SCD) and the associations of DFC and topological properties with cognitive performance.Methods: Thirty-three control subjects and 32 SCD individuals were enrolled in this study, and neuropsychological evaluations and resting-state functional magnetic resonance imaging scanning were performed. Thirty-three components were selected by group independent component analysis to construct 7 functional networks. Based on the sliding window approach and k-means clustering, distinct DFC states were identified. We calculated the temporal properties of fractional windows in each state, the mean dwell time in each state, and the number of transitions between each pair of DFC states. The global and local static parameters were assessed by graph theory analysis. The differences in DFC and topological metrics, and the associations of the altered neuroimaging measures with cognitive performance were assessed.Results: The whole cohort demonstrated 4 distinct connectivity states. Compared to the control group, the SCD group showed increased fractional windows and an increased mean dwell time in state 4, characterized by hypoconnectivity both within and between networks. The SCD group also showed decreased fractional windows and a decreased mean dwell time in state 2, dominated by hyperconnectivity within and between the auditory, visual and somatomotor networks. The number of transitions between state 1 and state 2, between state 2 and state 3, and between state 2 and state 4 was significantly reduced in the SCD group compared to the control group. No significant differences in global or local topological metrics were observed. The altered DFC properties showed significant correlations with cognitive performance.Conclusion: Our findings indicated DFC network reconfiguration in the SCD stage, which may underlie the early cognitive decline in SCD subjects and serve as sensitive neuroimaging biomarkers for the preclinical detection of individuals with incipient Alzheimer's disease.

Individuals with subjective cognitive decline (SCD) are at higher risk of incipient Alzheimer's disease (AD). Spatial navigation (SN) impairments in AD dementia and mild cognitive impairment patients have been well-documented; however, studies investigating SN deficits in SCD subjects are still lacking. This study aimed to explore whether basal forebrain (BF) and entorhinal cortex (EC) atrophy contribute to spatial disorientation in the SCD stage. In total, 31 SCD subjects and 24 normal controls were enrolled and administered cognitive scales, a 2-dimensional computerized SN test, and structural magnetic resonance imaging (MRI) scanning. We computed the differences in navigation distance errors and volumes of BF subfields, EC, and hippocampus between the SCD and control groups. The correlations between MRI volumetry and navigation distance errors were also calculated. Compared with the controls, the SCD subjects performed worse in both egocentric and allocentric navigation. The SCD group showed volume reductions in the whole BF (p < 0.05, uncorrected) and the Ch4p subfield (p < 0.05, Bonferroni corrected), but comparable EC and hippocampal volumes with the controls. In the SCD cohort, the allocentric errors were negatively correlated with total BF (r = −0.625, p < 0.001), Ch4p (r = −0.625, p < 0.001), total EC (r = −0.423, p = 0.031), and left EC volumes (r = −0.442, p = 0.024), adjusting for age, gender, years of education, total intracranial volume, and hippocampal volume. This study demonstrates that SN deficits and BF atrophy may be promising indicators for the early detection of incipient AD patients. The reduced BF volume, especially in the Ch4p subfield, may serve as a structural basis for allocentric disorientation in SCD subjects independent of hippocampal atrophy. Our findings may have further implications for the preclinical diagnosis and intervention for potential AD patients.

Background: Probiotics have been associated with the treatment of depression and anxiety. However, the results reported in the literature have been inconsistent, and no meta-analysis specifically reported probiotics used on participants with varying levels of emotional state.Methods: This meta-analysis aimed to study the effectiveness of probiotics on anxious or depressive symptomatology for participants under stress conditions or with a depressive or anxiety disorder diagnosis. Medline, PubMed, EMBASE, and the Cochrane Library were searched through December 2019 for randomized controlled trials (RCTs). The primary outcomes were depression and anxiety scores. Main inclusion criteria: RCTs of probiotics for participants with a mood or emotional disorder diagnosis or under stress situations; and all participants were adults (age ≥16 years); Assessed by the modified Jadad assessment scale found seven high-quality studies and three low-quality studies.Results: Ten clinical trials (n = 685 total participants) were included based on the inclusion and exclusion criteria. All studies were assessed as low or moderate risk of bias. The meta-analysis showed that probiotics could significantly reduce the depression scale for patients with anxiety and depression, and healthy participants under stress. However, there was no significant difference between the probiotics and placebo groups in the reduction of patient anxiety scores, even if they are depressive or anxious patients or healthy participants under stress. Subgroup analysis revealed that probiotics had significant effect on depressive symptoms just in patients with depression, and no significant change in anxiety in patients, and no improvement in participant performance under stress.Conclusions: Probiotics could alleviate depressive symptoms in patients with a depression diagnosis or depression scores also in anxiety disorder diagnosis, and suggesting that probiotics may be adjunct therapies for mood or emotional disorders. Therefore, it is essential that probiotics could be more involved in the treatment of patients with depression in the future. The evidence of probiotics successfully treating depression is still insufficient, and more high-quality studies on patients with depression are still needed.

The traditional Chinese medicine Shen-ling-bai-zhu-san (SLBZS) is described in “Tai Ping Hui Min He Ji Ju Fang.” SLBZS has been shown to be effective against many gastrointestinal diseases. The present study aimed to investigate the effect of SLBZS on experimental colitis in mice and to define the potential mechanisms. Our data suggest that compared to the model group, SLBZS treatment increases mouse body weight and colon length, decreases the DAI score, and improves colonic injury. SLBZS reduces the production of cytokines (IL-1β, IL-18, and TNF-α) in colon tissue and mouse colonic mucosal epithelial (MCME) cells. Mechanistically, SLBZS inhibits inflammation by inhibiting the MAPK and NF-κB signaling pathways. Further mechanistic analyses showed that SLBZS attenuates the expression levels of pyroptosis-related genes, including NLRP3, ASC, and GSDMD-N in the colons of mice. In addition, SLBZS restores the levels of the colon tight junction proteins ZO-1 and occludin, suggesting that it protects colonic barrier integrity and ameliorates the progression of colitis. In this paper, we demonstrate that SLBZS attenuates DSS-induced ulcerative colitis injury in mice via the MAPK/NF-κB and pyroptosis signaling pathway. These results indicate that SLBZS is a potential drug for the treatment of UC.