Multi-parameter MRI-Based Machine Learning Model to Evaluate the Efficacy of STA-MCA Bypass Surgery for Moyamoya Disease: A Pilot Study.

Superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery represents the primary treatment for Moyamoya disease (MMD), with its efficacy contingent upon collateral vessel development. This study aimed to develop and validate a machine learning (ML) model for the non-invasive assessment of STA-MCA bypass surgery efficacy in MMD. This study enrolled 118 MMD patients undergoing STA-MCA bypass surgery. Clinical features were screened to construct a clinical model. MRI features were extracted from the middle cerebral artery supply area using 3D Slicer and employed to build five ML models using logistic regression algorithm. The combined model was developed by integrating the radiomics score (Rad-score) with the clinical features. Model performance validation was conducted using ROC curves. Platelet count (PLT) was identified as a significant clinical feature for constructing the clinical model. A total of 3404 features (851 × 4) were extracted, and 15 optimal features were selected from each MRI sequence as predictive factors. Multivariable logistic regression identified PLT and Rad-score as independent parameters used for constructing the combined model. In the testing set, the AUC of the T1WI ML model [0.84 (95% CI, 0.70-0.97)] was higher than that of the clinical model [0.66 (95% CI, 0.46-0.86)] and the combined model [0.80 (95% CI, 0.66-0.95)]. The T1WI ML model can be used to assess the postoperative efficacy of STA-MCA bypass surgery for MMD.

DNA methylation of skeletal muscle function-related secretary factors identifies FGF2 as a potential biomarker for sarcopenia.

BACKGROUND: Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample-based methylation changes of skeletal muscle function-related factors in patients with sarcopenia. METHODS: The overall DNA methylation levels were analysed by using MethlTarget™ DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged ≥65 years) and 50 age- and sex-matched non-sarcopenic individuals. The candidate differentially methylated regions (DMRs) were further validated by Methylation-specific PCR (MSP) in another two independent larger sets and confirmed by pyrosequencing. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut-off levels of fibroblast growth factor 2 (FGF2)_30 methylation best predicting sarcopenia and area under the ROC curve (AUC) was measured. The correlation between candidate DMRs and the risk of sarcopenia was investigated by univariate analysis and multivariate logistic regression analysis. RESULTS: Among 1149 cytosine-phosphate-guanine (CpG) sites of 27 skeletal muscle function-related secretary factors, 17 differentially methylated CpG sites and 7 differentially methylated regions (DMRs) were detected between patients with sarcopenia and control subjects in the discovery set. Further methylation-specific PCR identified that methylation of fibroblast growth factor 2 (FGF2)_30 was lower in patients with sarcopenia and the level was decreased as the severity of sarcopenia increased, which was confirmed by pyrosequencing. Correlation analysis demonstrated that the methylation level of FGF2_30 was positively correlated to ASMI (r = 0.372, P < 0.001), grip strength (r = 0.334, P < 0.001), and gait speed (r = 0.411, P < 0.001). ROC curve analysis indicated that the optimal cut-off value of FGF2_30 methylation level that predicted sarcopenia was 0.15 with a sensitivity of 84.6% and a specificity of 70.1% (AUC = 0.807, 95% CI = 0.756-0.858, P < 0.001). Multivariate logistic regression analyses showed that lower FGF2_30 methylation level (<0.15) was significantly associated with increased risk of sarcopenia even after adjustment for potential confounders including age, sex, and BMI (adjusted OR = 9.223, 95% CI: 6.614-12.861, P < 0.001). CONCLUSIONS: Our results suggest that lower FGF2_30 methylation is correlated with the risk and severity of sarcopenia in the older adults, indicating that FGF2 methylation serve as a surrogate biomarker for the screening and evaluation of sarcopenia.

Prognostic value of cell division cycle-associated protein-3 in prostate cancer.

BACKGROUND: The study was aimed to explore cell division cycle-associated protein-3 (CDCA3) expression and its correlation with clinicopathological characteristics, and identification of co-expressed genes of CDCA3 in prostate cancer (PCa). METHODS: Data for CDCA3 mRNA expression in PCa were obtained from The Cancer Genome Atlas database. Furtherly, CDCA3 protein expression was examined by immunohistochemistry in 80 cases, including 20 normal prostate samples and 60 PCa samples. Then we used "survival" package to obtain the differentially expressed CDCA3 mRNA associated with prognosis of PCa patients. "pROC" package was used to analyze receiver operating characteristic of CDCA3. We used chi-square test, Kruskal-Wallis test and Wilcoxon rank sum test to identify clinicopathological parameters that correlated with CDCA3 expression. In order to determine the effects of CDCA3 expression and clinicopathological parameters on survival, univariate cox regression analysis was performed. Finally, the co-expressed genes of CDCA3 in PCa were explored by search tool for the retrieval of interacting genes, Kyoto encyclopedia of genes and genomes enrichment analysis and Spearman correlation analysis. RESULTS: In this study, we found that CDCA3 expression was increased in PCa. PCa patients with higher CDCA3 expression had poor outcomes. In terms of receiver operating characteristic, CDCA3 had an area under the curve of 0.857. High CDCA3 expression was positively correlated with advanced T stage, N stage, Gleason score, and served as an independent predictor of progress free interval in PCa patients. Then 20 proteins closely related to CDCA3 were screened through STRING website. Functional enrichment analysis revealed that, Kyoto encyclopedia of genes and genomes pathway was mainly enriched in cell cycle, including 6 genes, BUB1, CCNA2, CDK1, CDC20, TTK, and CCNB2. CONCLUSION: CDCA3 is significantly associated with the prognosis of PCa, which may be an indicator of the diagnosis and prognosis of PCa and a new therapeutic target.

Comparative Responses of Silicon to Reduce Cadmium and Enrich Selenium in Rice Varieties.

Cadmium (Cd), a highly toxic heavy metal for crops in China, poses a significant threat to rice cultivation. It is crucial to identify the genotypes with robust resistance to heavy metals, including Cd, in rice. The experiment was conducted to examine the mitigation effect of silicon (Si) on Cd toxicity levels in Se-enriched Z3055B and non-Se-enriched G46B rice genotypes. A basal dose of Si improved the growth and the quality of rice significantly by reducing the Cd content in rice roots, stems, leaves and grains and increased the yield, biomass and selenium (Se) content of brown rice in both genotypes. Additionally, Se content in brown rice and polished rice was notably higher in Se-enriched rice than in non-Se-enriched rice, with the highest amount at 0.129 mg/kg and 0.085 mg/kg, respectively. The results demonstrated that a basal fertilizer concentration of 30 mg/kg of Si was more effective in reducing Cd transport from roots to shoots in Se-enriched rice than in non-Se-enriched rice genotypes. Therefore, it can be concluded that Se-enriched rice genotypes are a viable option for food crop production in Cd-contaminated areas.

Dipeptidyl peptidase 4 as a potential serum biomarker for disease activity and treatment response in rheumatoid arthritis.

BACKGROUND: The treatment of rheumatoid arthritis (RA) related to the disease activity. However, the lack of highly sensitive and simplified markers limits the evaluation of disease activity. We sought to explore potential biomarkers associated with disease activity and treatment response in RA. METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis was performed to determine the differentially expressed proteins (DEPs) in serum collected from RA patients with moderate or high disease activity (determined by DAS28) before and after 24 weeks of treatment. Bioinformatic analysis were performed for DEPs and hub proteins. In the validation cohort, 15 RA patients were enrolled. Key proteins were validated by enzyme-linked immunosorbent assay (Elisa), correlation analysis and ROC curve. RESULTS: We identified 77 DEPs. The DEPs enriched in humoral immune response, blood microparticle, and serine-type peptidase activity. KEGG enrichment analysis displayed that the DEPs were significantly enriched in cholesterol metabolism and complement and coagulation cascades. Activated CD4 + T cell, T follicular helper cell, natural killer cell, and plasmacytoid dendritic cell significantly increased after treatment. Fifteen hub proteins were screened out. Among them, dipeptidyl peptidase 4 (DPP4) was the most significant protein associated with clinical indicators and immune cells. Serum concentration of DPP4 was testified to significantly increase after treatment and inversely correlate with disease activity indicators (ESR, CRP, DAS28-ESR, DAS28-CRP, CDAI, SDAI). Significant reduction was found in the serum CXC chemokine ligand10 (CXC10) and CXC chemokine receptor 3 (CXCR3) after treatment. CONCLUSIONS: Overall, our results suggest that serum DPP4 might be a potential biomarker for disease activity assessment and treatment response of RA.

Yishen-tongbi decoction inhibits excessive activation of B cells by activating the FcγRIIb/Lyn/SHP-1 pathway and attenuates the inflammatory response in CIA rats.

Rheumatoid arthritis (RA) is a chronic autoimmune disease. Strong evidence supports that excessive activation of B cells plays a critical role in the pathogenesis of RA. Fc gamma receptor b (FcγRIIb) is the B cell inhibitory receptor and inhibits BCR (B cell receptor) signalling in part by selectively dephosphorylating CD19 which is considered a co-receptor for BCR and is essential for B cell activation. Our previous study demonstrated that a FcγRIIb I232T polymorphism presented a strong genetic link to RA and may lead to the excessive activation of B cells. Therefore, novel therapeutic strategies and drugs that can effectively inhibit the excessive activation of B cells by regulating the FcγRIIb are necessary for the treatment of RA. Therefore, we used Burkitt's lymphoma ST486 human B cells (lacking endogenous FcγRIIb) transfected with the 232Thr loss-of-function mutant to construct a FcγRIIb mutant cell line (ST486), and we demonstrated that YSTB treatment not only reduced proliferation and promoted apoptosis in ST486 cells but also did so in a dose-dependent manner. Furthermore, the intracellular Ca2+ flux of ST486 cells was decreased after treatment with YSTB, inhibiting the excessive activation of ST486 cells, and these effects correlated with the CD19/FcγRIIb-Lyn-SHP-1 pathways. Our data showed that YSTB treatment inhibited the expression of phosphorylated CD19 and upregulated the protein expression of FcγRIIb, Lyn, and SHP-1. Additionally, the CIA model was established to explore the anti-inflammatory and inhibitory effects of YSTB on bone destruction, and we found that YSTB decreased the paw oedema and arthritis index (AI) in CIA rats. It is worth mentioning that YSTB clearly decreased the AI earlier than methotrexate (MTX) (day 10 vs 16). Moreover, synovial hyperplasia, inflammatory cell infiltration and cartilage surface erosion in CIA rats were noticeably reduced after treatment with YSTB as evidenced by histopathological examination. Finally, we found that YSTB treatment suppressed bone erosion and joint space score (JNS) in CIA rats as evidenced by radiographic assessment. In summary, these data suggest that YSTB has great therapeutic potential for RA treatment.

Hydrophobin-enhanced stability, dispersions and release of curcumin nanoparticles in water.

Most chemotherapeutic drugs commonly suffer from low aqueous solubility that can potentially limit drugs absorption. Drug nanomerization is an advanced approach to overcoming their poor water-solubility. In this study, class I hydrophobin recombinant HGFI (rHGFI)-based curcumin (Cur) nanoparticles (rHGFI-Cur) were prepared by freeze-drying method. The rHGFI-Cur nanocomposites were characterized by contact angle, transmission electron microscopy, fluorescence microscopy and dynamic light scattering. The results showed that rHGFI could lead to the wettability conversion and stability improved of Cur in water. X-ray photoelectron spectroscopy and Fourier transform infrared suggested that rHGFI could non-covalently bind to Cur to render them hydrophilic through hydrophobic forces. Additionally, drug release and cytotoxicity assays illustrated that rHGFI-Cur nanoparticles could facilitate Cur release and exhibited higher cytotoxicity than free Cur for human esophageal cancer cells TE-1. Thus, it suggested that rHGFI has a great potential application for hydrophobic drug delivery without toxicity.[Formula: see text].

Lemongrass (Cymbopogon citratus) oil: A promising miticidal and ovicidal agent against Sarcoptes scabiei.

BACKGROUND: Essential oils may represent an alternative strategy for controlling scabies, a neglected tropical disease caused by the infestation of mite from the species Sarcoptes scabiei. Lemongrass (Cymbopogen citratus) oil is reported to possess pharmacological properties including antiparasitc, antioxidant, antimicrobial and anti-inflammatory. The aim of the present study was to assess the potential efficacy of lemongrass oil against the mites and eggs of Sarcoptes scabiei. METHODOLOGY/PRINCIPAL FINDINGS: Mass spectrometry analysis confirmed that the main component presented in lemongrass oil was citral. Lemongrass oil at concentrations of 10% and 5% killed all Sarcoptes mites within 10 and 25 min, respectively. The median lethal concentration value was 1.37%, 1.08%, 0.91%, 0.64%, and 0.48% at 1, 3, 6, 12, and 24 h, respectively. Lemongrass oil at all concentrations (10%, 5%, 1%, 0.5%, 0.1%) was able to significantly decrease the hatching rate of Sarcoptes eggs. CONCLUSIONS/SIGNIFICANCE: Lemongrass oil should be considered as a promising miticidal and ovicidal agent for scabies control.

Responses of Fresh-Cut Strawberries to Ethanol Vapor Pretreatment: Improved Quality Maintenance and Associated Antioxidant Metabolism in Gene Expression and Enzyme Activity Levels.

Strawberries were treated with different concentrations of ethanol vapor and then cut into four wedges and stored at 4 °C for 1 week. It was found that 4 mL/kg of ethanol was the optimal concentration to reduce the decrease of firmness and weight loss. Total phenolics content, total flavonoid and anthocyanin contents, antioxidant enzyme activities, and gene expression related to the antioxidant were elevated using the ethanol treatment. Ethanol vapor also suppressed microbial growth and promoted free radical (hydroxyl and DPPH) scavenging capacities and four kinds of esters and bioactive components in strawberry wedges. Moreover, ethanol enhanced antioxidant enzyme activities including superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) by activating related gene expression. The results of our research indicate that ethanol vapor has potential application in preserving quality and improving antioxidant capacity of fresh-cut strawberries.

Physiological and Transcriptomic Analysis Validates Previous Findings of Changes in Primary Metabolism for the Production of Phenolic Antioxidants in Wounded Carrots.

Wounding induces the accumulation of phenolic compounds in carrot. This study uses physiological and transcriptomic analysis to validate previous findings relating primary metabolism and secondary metabolites in wounded carrots. Our data confirmed that increased wounding intensity strengthened the accumulation of phenolics accompanied by enhancing respiration and showed the loss of fructose and glucose and the increase of energy status in carrots. In addition, transcriptomic evaluation of shredded carrots indicated that the respiratory metabolism, sugar metabolism, energy metabolism, and phenolic biosynthesis related pathways, such as "citrate cycle (TCA cycle)", "oxidative phosphorylation" and "phenylpropanoid biosynthesis", were activated by wounding. Also, the differentially expressed genes (DEGs) involved in the conversion of sugars to phenolics were extensively up-regulated after wounding. Thus, the physiological and transcriptomic data validate previous findings that wounding accelerates the primary metabolisms of carrot including respiratory metabolism, sugar metabolism, and energy metabolism to meet the demand for the production of phenolic antioxidants.

EMMPRIN Down-regulating miR-106a/b Modifies Breast Cancer Stem-like Cell Properties via Interaction with Fibroblasts Through STAT3 and HIF-1α.

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a heavily glycosylated protein and expresses in cancer cells widely, which plays important roles in tumor progression. However, the role of EMMPRIN in breast cancer stem-like cell properties by interaction with fibroblasts is not known. In the present study, we investigated the effects of fibroblasts on breast cancer stem-like cells. We found that fibroblasts activated by co-cultured breast cancer cells produced higher levels of EMMPRIN, which stimulated the stem-like cell specific, self-renewal and sphere-forming phenotype in breast cancer cells. Increased EMMPRIN expression in activated fibroblasts increased the expression of STAT3 and HIF-1α and showed cancer stem-like cell features in breast cancer cells. We also found that EMMPRIN could down-regulate miR-106a and miR-106b expression in breast cancer cells, which led to activating STAT3 and enhancing HIF-1α expression. Our results illustrated that EMMPRIN has an important role in breast cancer stem-like cells by activation STAT3/HIF-1α through interaction with cancer cells and fibroblasts. The study for the first time indicated that cancer cells and fibroblasts interaction promotes breast cancer cells showing stem-like cells through up-regulation EMMPRIN, and led to inhibiting miR-106a/b expression which targets both STAT3 and HIF-1α expression.

Left atrial myoxma presenting as headache in the pediatric patient.

BACKGROUND: Cardiac myxomas rarely occur in children or adolescents. In addition, it is even more rare for the adolescent patient to present with neurological symptoms only. Early diagnosis is difficult because the symptoms of left atrial myxoma are frequently nonspecific. If delayed or left undiagnosed, severe and fatal complications, such as systemic embolism, heart failure, and pulmonary hypertension, may occur. CASE REPORT: A 13-year-old girl was admitted to our resuscitation room because of loss of consciousness for the preceding 2 h; she had a longstanding history of headache and dizziness for the previous 18 months. Repeated investigations at her local hospital did not reveal any abnormalities. During this admission, routine chest x-ray study found an abnormal bulge of a segment of the pulmonary artery and elevated cardiac enzymes. Emergency bedside echocardiography was performed and revealed a myxoma in the left atria. Subsequent computed tomography head revealed cardiogenic cerebral embolism. When her condition was stable, the patient was taken to the operating room, where a tumorectomy was performed successfully. The patient was then treated with oral anticoagulants and an uneventful recovery was made. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In order to avoid delayed diagnosis and treatment of its potentially fatal complications, it is important for the emergency clinician to have a high level of suspicion for a cardiac myxoma when attending to young patients that present with syncope. We therefore recommend that, as routine practice, bedside echocardiography to be carried in the emergency department for young patients that present with syncope.

Reduction of fibrosis in dibutyltin dichloride-induced chronic pancreatitis using rat umbilical mesenchymal stem cells from Wharton's jelly.

OBJECTIVES: The objective of this study was to investigate the effects of rat umbilical cord mesenchymal stem cells (UCMSCs) from Wharton's jelly on dibutyltin dichloride (DBTC)-induced chronic pancreatitis (CP) and subsequent pancreatic fibrosis in rats. METHODS: A rat model of CP induced by DBTC was used. Male Sprague-Dawley rats were randomly divided into 4 groups: the control, DBTC, DBTC + UCMSCs, and control + UCMSC groups. Umbilical cord mesenchymal stem cells were administered intravenously on day 5 after the administration of DBTC. On days 14 and 28, the rats were evaluated morphologically and biochemically. The expression levels of inflammatory cytokines and chemokines in the pancreatic tissues of different groups were evaluated using quantitative real-time polymerase chain reaction. The activation of pancreatic stellate cells was estimated by immunochemistry and Western blot analysis of α-smooth muscle actin. RESULTS: Umbilical cord mesenchymal stem cells were detected in inflamed pancreatic tissues. Umbilical cord mesenchymal stem cell treatment improved the histological scores and alleviated the fibrosis of pancreas samples, The expression of cytokines in the DBTC + UCMSC group was significantly lower than that in the DBTC group. Also, pancreatic stellate cell activation was inhibited by UCMSC treatment. CONCLUSIONS: Xenogeneic transplantation of UCMSCs is a novel approach for the treatment of CP and subsequent fibrosis. Umbilical cord mesenchymal stem cells may be a promising therapeutic intervention for human CP in the future.