Diagnostic and Predictive Value of LncRNA MCM3AP-AS1 in Sepsis and Its Regulatory Role in Sepsis-Induced Myocardial Dysfunction.

The present study focused on exploring the clinical value and molecular mechanism of LncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) in sepsis and sepsis-induced myocardial dysfunction (SIMD). 122 sepsis patients and 90 healthy were included. Sepsis patients were categorized into SIMD and non-MD. The expression levels of MCM3AP-AS1 and miRNA were examined using RT-qPCR. Diagnostic value of MCM3AP-AS1 in sepsis assessed by ROC curves. Logistic regression to explore risk factors influencing the occurrence of SIMD. Cardiomyocytes were induced by LPS to construct cell models in vitro. CCK-8, flow cytometry, and ELISA to analyze cell viability, apoptosis, and inflammation levels. Serum MCM3AP-AS1 was upregulated in patients with sepsis. The sensitivity and specificity of MCM3AP-AS1 were 75.41% and 93.33%, for recognizing sepsis from healthy controls. Additionally, elevated MCM3AP-AS1 is a risk factor for SIMD and can predict SIMD development. Compared with the LPS-induced cardiomyocytes, inhibition of MCM3AP-AS1 significantly attenuated LPS-induced apoptosis and inflammation; however, this attenuation was partially reversed by lowered miR-28-5p, but this reversal was partially eliminated by CASP2. MCM3AP-AS1 may be a novel diagnostic biomarker for sepsis and can predict the development of SIMD. MCM3AP-AS1 probably participated in SIMD progression by regulating cardiomyocyte inflammation and apoptosis through the target miR-28-5p/CASP2 axis.

A review on micro- and nanoplastics in humans: Implication for their translocation of barriers and potential health effects.

As emerging contaminants, micro- and nanoplastics (MNPs) can absorb and leach various toxic chemicals and ultimately endanger the health of the ecological environment and humans. With extensive research on MNPs, knowledge about MNPs in humans, especially their translocation of barriers and potential health effects, is of utmost importance. In this review, we collected literature published from 2000 to 2023, focusing on MNPs on their occurrence in humans, penetrating characteristics in the placental, blood-brain, and blood-testis barriers, and exposure effects on mammalian health. The characteristics and distributions of MNPs in human samples were analyzed, and the results demonstrated that MNPs were ubiquitous in most human samples, except for kidneys and cerebrospinal fluid. In addition, the phenomenon of MNPs crossing barriers and their underlying mechanisms were discussed. We also summarized the potential factors that may affect the barrier crossing and health effects of MNPs, including characteristics of MNPs, exposure doses, administration routes, exposure durations, co-exposure to other pollutants, and genetic predisposition. Exposure to MNPs may cause cytotoxicity, neurotoxicity, and developmental and reproductive toxicity in mammals. People are encouraged to reduce their exposure to MNPs to prevent these adverse health effects. Finally, we discussed the shortcomings of current research on MNPs in humans, providing a valuable reference for understanding and evaluating the potential health risks from MNP exposure in mammals, including humans.

Eosinophilic granulomatous polyangiitis with central nervous system involvement in children: a case report and literature review.

Objective: To explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis (EGPA). Methods: A child who presented with EGPA complicated by CNS involvement was admitted to our hospital in June 2023. The clinical features were analyzed retrospectively, and relevant literatures were reviewed to provide a comprehensive overview of this condition. Results: A ten-year-old girl, who had a history of recurrent cough and asthma accompanied by peripheral blood eosinophilia for eight months, was admitted to our hospital. On admission, spotted papules were visible on her hands and feet, bilateral pulmonary rales were audible. The laboratory examination revealed that the proportion of eosinophils (EOS) exceeded 10% of white blood cells, the anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, the immunoglobulin G level was 15.80g/L, and the immunoglobulin E level was greater than 2500.00IU/mL. The imaging examination showed multiple patchy and nodular high-density shadows in both lungs as well as sinusitis. Pulmonary function tests indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology demonstrated a significant increase in the proportion of eosinophils. Skin pathology confirmed leukocytoclastic vasculitis. During the hospitalization, the child had a convulsion. The magnetic resonance imaging (MRI) scan of the brain showed multiple abnormal signal shadows in the bilateral cerebral cortex and the electroencephalogram (EEG) showed epileptic waves. Following the administration of methylprednisolone pulse therapy in combination with cyclophosphamide treatment, her cough and asthma resolved, the skin rash disappeared without any further convulsions. We found that only a young EGPA patient with CNS involvement had been previously reported. The previously reported case began with long-term fever, weight loss, and purpuric rash. Both patients responded well to treatment with glucocorticoids and cyclophosphamide, experiencing significant improvement in their clinical symptoms and normalization of their peripheral blood eosinophils. Conclusion: The diagnosis of EGPA in children can be challenging. When a child is affected by EGPA, it is essential to remain vigilant for signs of CNS involvement. The treatment with glucocorticoids and cyclophosphamide is effective in managing EGPA in children.

Elucidating the role of circNFIB in myocardial fibrosis alleviation by endogenous sulfur dioxide.

BACKGROUND: To investigate the role of circNFIB in the alleviation of myocardial fibrosis by endogenous sulfur dioxide (SO2). METHODS: We stimulated cultured neonatal rat cardiac fibroblasts with transforming growth factor-ß1 (TGF-ß1) and developed an in vitro myocardial fibrosis model. Lentivirus vectors containing aspartate aminotransferase 1 (AAT1) cDNA were used to overexpress AAT1, and siRNA was used to silence circNFIB. The SO2, collagen, circNFIB, Wnt/ß-catenin, and p38 MAPK pathways were examined in each group. RESULTS: In the in vitro TGF-ß1-induced myocardial fibrosis model, endogenous SO2/AAT1 expression was significantly decreased, and collagen levels in the cell supernatant and type I and III collagen expression, as well as α-SMA expression, were all significantly increased. TGF-ß1 also significantly reduced circNFIB expression. AAT1 overexpression significantly reduced myocardial fibrosis while significantly increasing circNFIB expression. Endogenous SO2 alleviated myocardial fibrosis after circNFIB expression was blocked. We discovered that circNFIB plays an important role in the alleviation of myocardial fibrosis by endogenous SO2 by inhibiting the Wnt/ß-catenin and p38 MAPK pathways. CONCLUSION: Endogenous SO2 promotes circNFIB expression, which inhibits the Wnt/ß-catenin and p38 MAPK signaling pathways, consequently alleviating myocardial fibrosis.

Serum dual-specificity phosphatase 1 reflects decreased exacerbation risk, correlates with less advanced exacerbation severity and lower inflammatory cytokines in children with asthma.

BACKGROUND: It is as fact that dual-specificity phosphatase 1 (DUSP1) regulates the T cell activation, pro-allergic response, and inflammation to engage with the pathogenesis of asthma, but its clinical role in children with asthma is unclear. The present study aimed to explore the expression of DUSP1, its association with exacerbation risk, severity, and inflammatory cytokines in children with asthma. METHOD: Around 52 children with asthma-exacerbation, 50 children in asthma-remission, and 50 healthy children were chosen for the study. The serum levels of DUSP1, as well as tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-17 were detected by the enzyme-linked immunosorbent assay. RESULTS: The levels of DUSP1 was the highest in healthy children (median (IQR)=34.305 (25.892- 43.693) ng/mL), the second highest in children in asthma-remission (median (IQR)=21.471 (18.581-27.934) ng/mL), and the lowest in children with asthma-exacerbation (median (IQR)=13.982 (7.901-21.624) ng/mL) (P<0.001). At the same time, DUSP1 was also related to decreased asthma risk with area under curve (AUC) (95%CI) of 0.847 (0.780-0.914), and correlated with its lower exacerbation risk with AUC (95%CI) of 0.755 (0.661-0.849). Besides, DUSP1 was negatively linked with exacerbation severity (rs =-0.338, P=0.014), immunoglobulin E (rs =-0.277, P=0.047), TNF-α (rs =-0.423, P=0.002), IL-1ß (rs =-0.389, P=0.004), and IL-17 (rs =-0.293, P=0.035), but not related with other disease features in children with asthma-exacerbation. Meanwhile, DUSP1 was only negatively associated with TNF-α (rs=-0.300, P=0.034) and IL-1ß (rs =-0.309, P=0.029) in children in asthma-remission. However, no correlation was found in DUSP1 with inflammatory cytokines or other disease features in healthy children (all P>0.05). CONCLUSION: DUSP1 reflects the reduced exacerbation risk, and associates with lower exacerbation severity and inflammatory cytokines in children with asthma-exacerbation; it also associates with inflammatory cytokines in children in asthma-remission. These findings suggest that DUSP1 may help to improve the management of asthmatic children.

Microplastics in take-out food: Are we over taking it?

Take-out food has become increasingly prevalent due to the fast pace of people's life. However, few study has been done on microplastics in take-out food. Contacting with disposable plastic containers, take-out food may be contaminated with microplastics. In the present study, abundance and characteristics of microplastics in total of 146 take-out food samples including solid food samples and beverage samples (bubble tea and coffee) were determined and identified. The mean abundance of microplastics in take-out food was 639 items kg-1, with the highest value in rice and the lowest value in coffee. Fragments shape, transparent color and sizes ≤ 500 µm were the main characteristics of microplastics in those food, and polyethylene was the main polymer type. Our results indicated that microplastics in take-out food was influenced by food categories and cooking methods, as well as food packaging materials. Approximately 170-638 items of microplastics may be consumed by people who order take-out food 1-2 times weekly.

Therapeutic effect of the sulforaphane derivative JY4 on ulcerative colitis through the NF-κB-p65 pathway.

The efficacy of the sulforaphane derivative JY4 was evaluated in acute and chronic mouse models of ulcerative colitis induced by dextran sodium sulfate. Oral administration of JY4 led to significant improvements in symptoms, with recovery of body weight and colorectal length, together with reduced diarrhoea, bloody stools, ulceration of colonic tissue and infiltration of inflammatory cells. The oral bioavailability of JY4, determined by comparing oral dosing with injection into the tail vein, was 5.67%, which was comply with the idea in the intestinal function. Using a dual-luciferase reporter assay, immunofluorescence studies, western blot analysis and immunohistochemical staining, JY4 was shown to significant interfere with the NF-κB-p65 signaling pathway. By preventing the activation of NF-κB-p65, JY4 inhibited the overexpression of downstream inflammatory factors, thereby exerting an anti-inflammatory effect on the intestinal tract. This study thus provides a promising candidate drug, and a new concept for the treatment of ulcerative colitis.

A rapid method for extracting microplastics from oily food samples.

The increasing evidence of microplastic (MP) contamination influence on aquatic organisms has been extensively reported globally. However, the discussions of extracting MPs from oily food samples are limited, highlighting the pressing need for effective and standardized analytical methods to extract MPs from oily food. Previous methods, such as using acid, alkali or oxidizing solutions as digestion reagents, usually take a long time to digest oily food, increasing the possibility of procedural contamination of MPs in food over time. The objective of this study was to develop a rapid, efficient, economical and simple analytical method to extract MPs from oily food samples. This innovative protocol combines the use of 4 : 1 HNO3 : H2O2 as a digestion reagent to accelerate the digestion within 1 h at 50 °C and hexane as a washing solution to remove the oil adsorbed on the surface of MPs and membranes. Four common types of MPs, namely, polyethylene terephthalate, polyethylene, polystyrene and polypropylene of different sizes were added to oily flours to demonstrate this method. The mean recovery of MPs was 95% ± 2% (range: 93-98%), and no significant changes in color, particle size, surface area and spectrum features were found for all recovered polymers except for PS with minor changes in color and surface. The method was confirmed to be effective on rice, noodles, bean products and various meat samples. All in all, the present method can facilitate the observation and identification of characteristics of MPs, providing an innovative combination method for quantitative and qualitative analyses of MPs in oily food samples.

JNK pathway-associated phosphatase illustrates low expression and negative correlations with inflammation, disease activity, and T-helper 17 cells in inflammatory bowel disease children.

BACKGROUND: C-Jun N-terminal kinase pathway-associated phosphatase (JKAP) modulates the T cell receptor and mitogen-activated protein kinase pathway-mediated autoimmunity, thus participating in the pathogenesis of autoimmune diseases. This study aimed to explore the clinical implication of JKAP in inflammatory bowel disease (IBD) children. METHODS: C-Jun N-terminal kinase pathway-associated phosphatase, tumor necrosis factor-α (TNF-α), interleukin-23, interferon-γ (T-helper 1 secreted cytokine), and interleukin-17A (T-helper 17 secreted cytokine) in serum samples from 140 IBD children (including 60 Crohn's disease (CD) children and 80 ulcerative colitis (UC) children) were detected by ELISA. Meanwhile, JKAP from serum samples of 10 healthy controls (HCs) was also detected by ELISA. RESULTS: C-Jun N-terminal kinase pathway-associated phosphatase was reduced in CD children (median (interquartile range (IQR)): 51.6 (36.8-69.5) pg/ml) and UC children (median (IQR): 57.5 (43.4-78.5) pg/ml) compared with HCs (median (IQR): 101.8 (70.0-143.2) pg/ml) (both p < 0.05). In CD children, JKAP was negatively correlated with C-reactive protein (CRP) (p = 0.016) and erythrocyte sedimentation rate (ESR) (p = 0.029); while in UC children, JKAP was also negatively correlated with CRP (p = 0.006) and ESR (p = 0.022). Regarding the correlation of JKAP with disease activity, it presented negative correlations with PCDAI (p = 0.001) and PUCAI (p = 0.002). Besides, JKAP was negatively related to TNF-α (both p < 0.05) but not interleukin-23 (both p>0.05) in CD and UC children. Additionally, JKAP was not correlated with interferon-γ in CD or UC children (both p>0.05), while negatively correlated with interleukin-17A in CD and UC children (both p < 0.05). CONCLUSION: C-Jun N-terminal kinase pathway-associated phosphatase shows low expression and negative correlations with inflammation, disease activity, and T-helper 17 cells in IBD children.

Gamma-Glutamyltransferase Activity (GGT) Is a Long-Sought Biomarker of Redox Status in Blood Circulation: A Retrospective Clinical Study of 44 Types of Human Diseases.

Methods: The clinical GGT data from 168,858 patients with 44 diseases and 132,357 healthy control in the clinical laboratory of our hospital over the past five years were retrieved. All data were analyzed with SPSS, RStudio V.1.3.1073, and python libraries 3.8. Results: Thirty-eight out of 44 diseases had significantly increased (p < 0.001) circulating GGT activities, whereas gastric cancer, anemia, renal cyst, cervical cancer, preeclampsia, and knee-joint degenerative diseases had significantly decreased (p < 0.001) GGT activities compared to the healthy control. ROC analyses showed that GGT was an excellent biomarker for liver cancer (AUC = 0.86), pancreatitis (AUC = 0.84), or hepatic encephalopathy (AUC = 0.80). All pancreas-related diseases had more than 8-fold increases in GGT activity span than the healthy control, while pancreatic cancer had a 12-fold increase (1021 U/L vs. 82 U/L). The knee-joint degenerative disease had the lowest median and narrowest GGT activity range (63 U/L). Furthermore, most diseases' lowest to highest GGT activities were beyond the healthy control in both directions. Conclusions: Thirty-eight out of 44 diseases were in overall oxidative states defined by the increased GGT median values. In contrast, knee-joint degenerative disease, gastric cancer, anemia, renal cyst, cervical cancer, and preeclampsia were in overall antioxidative states. Moreover, most diseases swing between oxidative and antioxidative states, evidenced by the increased lowest to highest GGT activity ranges than the healthy control. Liver- and pancreas-related abnormalities were responsible for significantly increased GGT activities. Our overall results suggested that circulating GGT was a redox status biomarker.

Synthesis of ponatinib analogues as novel inhibitors of leukemia stem cells.

Aim: To synthesize new analogues of ponatinib and evaluate anti-leukemia cells and cytotoxicity. Methodology & results: The inhibitory activity of compounds 13a and 13c against K562 and HL60 cells was comparable to that of ponatinib (IC50 = 0.74, 0.88 vs 0.64 nM and 0.59, 0.77 vs 0.39 nM, respectively). Compounds 13a and 40b were 34- and 77-fold more potent than ponatinib against KG1a cells (IC50 = 0.091 and 0040 vs 3.6 µM, respectively). Compounds 13a, 13c and 40b also decreased the Abl protein level in the K562 cells, inhibited colony formation in MCF-7 cells and inhibited cell migration in B16BL6 cells. Compound 13a showed low cytotoxicity in 293 cells. Conclusion: Compound 13a was the best lead compound.

Relationships between athletic ability and academic performance in primary school students: A 3-year follow-up study.

Background: The aim of this study was to examine whether academic performance is associated with students' athletic ability in primary school. Methods: A 3-year follow-up study was conducted among 1,136 Chinese students. Sit-up and jump rope testers were used to measure 1-min sit-ups and 1-min jump ropes, respectively. Meanwhile, the Pittsburgh Sleep Quality Scale and the Beck Depression Inventory were used to estimate sleep quality and depression levels. The end-of-semester examinations were used to evaluate students' academic performance during the follow-up period. Results: After adjusting for confounders, the mean change in Chinese language performance for participants stratified by 1-min sit-ups at baseline was 0.35 (95% CI: -0.37 to 0.76) for level 1 (slowest), 0.52 (95% CI: -0.54 to 1.08) for level 2, and 1.72 (95% CI: 1.14 to 2.30) for level 3 (fastest) (P for trend = 0.003); the mean change in math scores was 0.28 (95% CI: -0.50 to 0.95) for level 1 (slowest), 0.95 (95% CI: 0.38 to 1.52) for level 2, and 1.41 (95% CI: 0.82 to 1.99) for level 3 (fastest) (P for trend = 0.048). The mean change in foreign language scores was -0.45 (95% CI: -0.99 to -0.93) for level 1 (slowest), -0.14 (95% CI: -0.44 to 0.41) for level 2, and 0.69 (95% CI: 0.25 to 1.13) for level 3 (fastest) (P for trend = 0.004). The mean change in Chinese language performance for participants stratified by 1-min jump ropes at the baseline was 0.30 (95% CI: -0.16 to 0.76) for level 1 (slowest), 1.09 (95% CI: 0.42 to 1.76) for level 2, and 1.74 (95% CI: 1.14 to 2.35) for level 3 (fastest) (P for trend = 0.001). The mean change in math scores was 0.41 (95% CI: -0.11 to 0.92) for level 1 (slowest), 1.44 (95% CI: 0.69 to 2.19) for level 2, and 1.43 (95% CI: 0.76 to 2.10) for level 3 (fastest) (P for trend = 0.019). The mean change in foreign language performance was -0.71 (95% CI: -1.08 to -0.33) for level 1 (slowest), 0.95 (95% CI: -0.40 to 1.50) for level 2, and 0.91 (95% CI: 0.41 to 1.41) for level 3 (fastest) (P for trend < 0.001). Conclusion: This study suggests that participation in jump rope and sit-up exercises may positively affect students' academic performance.

[Identification of crucial areas of water supply service in Shiyang River Basin based on service flow]. / åŸºäºŽæœåŠ¡æµçš„çŸ³ç¾Šæ²³æµåŸŸæ°´ä¾›ç»™æœåŠ¡å ³é”®åŒºåŸŸè¯†åˆ«.

The identification of crucial areas of ecosystem service is of great significance for accurate implementation of sustainable development measures and the improvement of regional ecosystem service. Taking Shiyang River Basin as a research unit, we analyzed the spatio-temporal variations of the provision and consumption of water supply services in 2005, 2010, 2015, and 2020. The water supply service flow model was used to quantitatively simulate water supply service flow. The ZONATION model was selected to identify the crucial areas in the Shiyang River Basin in 2020. The results showed that the provision of water supply services in the Shiyang River Basin showed a spatial pattern being high in the south and low in the north from 2005 to 2020, which declined gradually with time. The consumption showed a spatial pattern dominated by cultivated land and industrial land and temporal change with a downward trend in fluctuation. Each year, about 10.8% of water demand gap could be made up by replenishing upstream water resource. In 2020, the crucial areas of water supply service in Shiyang River Basin were 14455 km2. We proposed management strategies to repair and improve the capacity of water conservation, flow promotion, and water conservation in crucial areas from the perspective of provision, transmission, and consumption.

Efficacy and safety of belimumab for the treatment of refractory childhood-onset systemic lupus erythematosus: A single-center, real-world, retrospective study.

Objective: This study aimed to investigate the efficacy and safety of belimumab for treating children with refractory childhood-onset systemic lupus erythematosus (cSLE). Methods: Twenty-six cSLE patients who received belimumab treatment in our hospital from January 2020 to September 2021 (23 of them for more than 52 weeks) were enrolled in this study. Their clinical and laboratory data, assessment of disease activity, glucocorticoid dosage, and treatment-emergent adverse events (TEAEs) were retrieved for analysis. The paired samples t-test and the nonparametric test were used to compare the baseline and post-treatment data. Results: The mean age of onset was 10.3 ± 2.4 years old; the mean disease duration was 41.6 ± 37.4 months; the median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 10 (P 25, P 75: 3, 17); and the mean Physician's Global Assessment (PGA) score at baseline was 1.9 ± 1.0. Compared with the baseline values, there was a significant decrease in the 24-h urine protein quantifications at 24 and 52 weeks of treatment (P<0.05) as well as an elevated complement (C) 3 and C4 levels at 4, 12, 24, and 52 weeks of treatment. In addition, the SLEDAI-2K and PGA scores as well as the percentage of CD19+ B cells were significantly decreased at 12, 24, and 52 weeks of treatment compared with the baseline values (P<0.05). The dosage of glucocorticoid at 4, 12, 24, and 52 weeks of treatment was significantly less than that at baseline or the previous follow-up (P<0.05). At 52 weeks, 14 subjects (53.8%) achieved Lupus Low Disease Activity State (LLDAS), and 4 subjects (15.4%) reached clinical remission (CR). At the last follow-up, 16 subjects (61.5%) achieved LLDAS, and 10 subjects (38.5%) reached CR. Conclusions: Belimumab treatment can significantly improve laboratory indicators, reduce disease activity, and decrease the dosage of glucocorticoid required in children with cSLE. Moreover, it has a good safety profile.

Microplastics: A review of analytical methods, occurrence and characteristics in food, and potential toxicities to biota.

Microplastics (MPs) are ubiquitous in various environment compartments, including food. Here, we collected research reports of MPs in food published during 2010-2020, and summarized the analytical methods developed and utilized by researchers (e.g., digestion, separation and identification, as well as related QA/QC measures implemented), the occurrence, and the characteristics of MPs in six kinds of food. The potential effects on biota from exposure to MPs were also reviewed. The results showed that most researchers digested food samples using chemical solutions such as HNO3, H2O2, KOH, or NaOH. FT-IR and Raman spectroscopy were the main technique for identifying MPs, and microscopes were used to count MP particles. The abundances MPs were in the ranges of 0-5860, 2.00-1100, 0-698, 4.00-18.7, 0-5.68 × 104 and 900-3000 particles/kg in beverages, condiments, honey, meat, seafood and vegetables, respectively. The "maximum" annual human intake of MPs from these foods is approximately 1.42 × 105-1.54 × 105 particles/capita, equivalent to the consumption of 50 plastic bags (size: 0.04 mm × 250 mm × 400 mm, density: 0.98 g/cm3) each year. Blue-colored and fiber-shaped MP particles were the most commonly observed in food, predominated by PA, PE, PES, PET and PP types. Toxicity studies indicated that MPs, additives of MPs and adsorbents or microorganisms on the surfaces of MPs were all somewhat toxic to cells or biota. Exposure to MPs may induce oxidative stress, inflammation, neurotoxicity, and reproductive toxicity, and change the structure of intestinal microflora in cells or biota. Therefore, we call for more investigation into the residual, excretion and bioavailability of MPs or related absorbents/additives in biota and humans.

Phthalate metabolites: Characterization, toxicities, global distribution, and exposure assessment.

Phthalates are plasticizers in various products and regarded as endocrine disruptors due to their anti-androgen effects. Environmental occurrence and toxicities of parent phthalates have been widely reported, while the current state of knowledge on their metabolites is rarely summarized. Based on the available literature, the present review mainly aims to 1) characterize the potential metabolites of phthalates (mPAEs) using the pharmacokinetics evidences acquired via animal or human models; 2) examine the molecular and cellular mechanism involved in toxicity for mPAEs; 3) investigate the exposure levels of mPAEs in different human specimens (e.g., urine, blood, seminal fluid, breast milk, amniotic fluid and others) across the globe; 4) discuss the models and related parameters for phthalate exposure assessment. We suggest there is subtle difference in toxic mechanisms for mPAEs compared to their parent phthalates due to their alternative chemical structures. Human monitoring studies performed in Asia, America and Europe have provided the population exposure baseline levels for typical phthalates in different regions. Urine is the preferred matrix than other specimens for phthalate exposure study. Among ten urinary mPAEs, the largest proportions of di-(2-ethylhexyl) phthalate (DEHP) metabolites (40%), monoethyl phthalate (mEP) (43%) and DEHP metabolites/mEP (both 29%) were observed in Asia, America and Europe respectively, and mono-5-carboxy-2-ethypentyl phthalate was the most abundant compounds among DEHP metabolites. Daily intakes of phthalates can be accurately calculated via urinary mPAEs if the proper exposure parameters were determined. Further work should focus on combining epidemiological and biological evidences to establish links between phthalates exposure and biological phenotypes. More accurate molar fractions (FUE) of the urinary excreted monoester related to the ingested diesters should be collected in epidemiological or pharmacokinetic studies for different population.

[The Effect and Mechanism of Novel Telomerase Inhibitor Nilo 22 on Leukemia Cells].

OBJECTIVE: To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells. METHODS: The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP+ cells was tested by colony-forming units assays (CFU). The cytotoxic effect was further detected by transplant assays ex vivo. Telomerase activity assay, C-circle assay were used to measure the effects of compound on the length mechanism of telomere, RT-PCR was used to detected the changes of telomere. RESULTS: Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP+ cells significantly, slightly arrests the cell cycle at G0/G1 phase, and significantly inhibits colony formation and prolong the progression in MLL-AF9 leukemia mice model. The expression showed that the compound could slow the disease progression in MLL-AF9 leukemia mice significantly. Mechanistically, Nilo 22 could reduce the length of telomere by inhibiting telomerase activity and alternative lengthening of telomere (ALT). CONCLUSION: Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.

Novel Fluorescent Probe toward Fe3+ Based on Rhodamine 6G Derivatives and Its Bioimaging in Adult Mice, Caenorhabditis elegans, and Plant Tissues.

A new fluorescent probe LXY based on the rhodamine 6G platforms has been designed, synthesized, and characterized, which could recognize Fe3+ effectively in HEPES buffer (10 mM, pH = 7.4)/CH3CN (2:3, v/v). And the distinct color change and the rapid emergence of fluorescence emission at 550 nm achieved "naked eye" detection of Fe3+. The interaction mode between them was achieved by Job's plot, MS, SEM, and X-ray single-crystal diffraction. Importantly, the crystal structures proved that Fe3+ could induce the rhodamine moiety transform the closed-cycle form to the open-cycle form. But it is interesting that Fe3+ did not appear in the crystal structures. Meanwhile, the limit of detection (LOD) of LXY to Fe3+ was calculated to be 3.47 × 10-9. In addition, the RGB experiment, test papers, and silica gel plates all indicated that the probe LXY could be used to distinguish Fe3+ quantitatively and qualitatively on-site. Moreover, the probe LXY has also been successfully applied to Fe3+ image in Caenorhabditis elegans, adult mice, and plant tissues. Thus, LXY was considered to have some potential for application in bioimaging.