KNTC1 knockdown inhibits the proliferation and migration of osteosarcoma cells by MCM2.

Osteosarcoma (OS) is a common primary malignant bone tumor, and it is necessary to further investigate the molecular mechanism of OS progression. The expression of kinetochore associated protein 1 (KNTC1) and minichromosome maintenance 2 (MCM2) was detected by immunohistochemistry, quantitative PCR (qPCR) and Western blot. Gene knockdown or overexpression cell models were constructed and the proliferation, apoptosis, cell cycle and migration were detected in vitro, besides, xenograft models were established to explore the effects of KNTC1 downregulation in vivo. Public databased and bioinformatics analysis were performed to screen the downstream molecules and determine the expression of MCM2 in cancers. KNTC1 was overexpressed in OS tissues and positively correlated with overall survival of OS patients. KNTC1 knockdown inhibited the proliferation and migration, and arrested G2 phase, and induced apoptosis. Besides, KNTC1 downregulation restricted the xenograft tumor formation. MCM2, one of the coexpressed genes, was highly expressed in sarcoma and downregulated after KNTC1 knockdown. MCM2 overexpression heightened the proliferation and migration ability of OS cells, which was reversed the inhibiting effects of KNTC1 knockdown. KNTC1 was overexpressed in OS and promoted the progression of OS by upregulating MCM2.

High histone crotonylation modification in bovine fibroblasts promotes cell proliferation and the developmental efficiency of preimplantation nuclear transfer embryos.

Lysine crotonylation (Kcr) is a recently discovered histone acylation modification that is closely associated with gene expression, cell proliferation, and the maintenance of stem cell pluripotency and indicates the transcriptional activity of genes and the regulation of various biological processes. During cell culture, the introduction of exogenous croconic acid disodium salt (Nacr) has been shown to modulate intracellular Kcr levels. Although research on Kcr has increased, its role in cell growth and proliferation and its potential regulatory mechanisms remain unclear compared to those of histone methylation and acetylation. Our investigation demonstrated that the addition of 5 mM Nacr to cultured bovine fibroblasts increased the expression of genes associated with Kcr modification, ultimately promoting cell growth and stimulating cell proliferation. Somatic cell nuclear transfer of donor cells cultured in 5 mM Nacr resulted in 38.1% blastocyst development, which was significantly greater than that in the control group (25.2%). This research is important for elucidating the crotonylation modification mechanism in fibroblast proliferation to promote the efficacy of somatic cell nuclear transfer.

Linkage and Stereochemistry Characters of Phenolic Antioxidant Product Formation.

The present study developed a smart and novel strategy to elucidate the linkage and stereochemistry characters during phenolic antioxidant product formation. A series of phenolic isomers or analogues were treated with 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide radical, to create 16 antioxidant dimerization reactions in aqueous solution. The products were rapidly identified by ultraperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass-spectrometry. Through a systematic function-structure relationship analysis of these reactions and theoretical calculations, it is concluded that the phenolic antioxidant product is formed via linear linkage or furanocyclic linkage. The linear linkage is fulfilled via a radical coupling and controlled by the O-O linkage exclusion, meta-linkage exclusion, and catechol-activated principles. However, when an exocyclic π-bond conjugates with the phenolic core and is affixed at the -OH para-position, the furanocyclic linkage may occur via a subsequent intramolecular Michael addition. The intramolecular addition always lacks Re-attack to show "α,ß diastereoselectivity." The α,ß diastereoselectivity is the stereochemistry character of furanocyclic linkage during phenolic antioxidant product formation. All these novel findings can benefit not only the field food science but also other fields as well.

Effect of ofloxacin levels on growth, photosynthesis and chlorophyll fluorescence kinetics in tomato.

Antibiotic pollution has become a global environmental pollution problem. Chlorophyll fluorescence is one of the most important indicators reflecting the degree to which plants are influenced by the environment. Ofloxacin (OFL) is a highly toxic antibiotic pollutant, and there are few reports on the effects of changes in OFL levels on tomato chlorophyll fluorescence parameters. In this study, we investigated the responses of tomato growth, photosynthetic activity and chlorophyll fluorescence kinetics to exogenous OFL exposure (as the concentrations of 0, 2.5, 5, 10 and 20 mg L-1). The results showed that lower concentrations of OFL (2.5 mg L-1) had little impact on tomato growth, while plant growth was inhibited with the OFL concentration increasing. At higher OFL concentrations (5, 10 and 20 mg L-1), chloroplasts ruptured, and chlorophyll became degraded, resulting in leaf etiolation. Furthermore, the photosynthetic and photochemical efficiency and electron transfer rate were significantly inhibited by OFL. Moreover, damage to the oxygen-evolving complex on the donor side of PSⅡ prevented electron transfer from QA to QB and led to photoinhibition. In conclusion, higher OFL concentration reduced photosynthesis by destroying the photosynthetic mechanism in tomato, resulting in tomato leaf etiolation and plant growth inhibition.

Detection of bile acids in small volume human bile samples via an amino metal-organic framework composite based solid-phase microextraction probe.

In recent years, bile acids (BAs), the important component of bile, were found closely related to the occurrence and development of diseases, therefore, determination of BAs in bile samples is of great significance. However, biological matrix complexity and low concentrations of BAs were still challenging for BA detection in small amount of bile samples. In this work, a core-shell NH2-MIL101@mSiO2 was designed to improve the capture ability of BAs in biological samples, as well as possess good biocompatibility. Subsequently, solid-phase microextraction (SPME) probe of the NH2-MIL101@mSiO2 was coupled with HPLC-MS/MS to establish the analysis method for detecting eight BAs in bile samples. The established method received extraction efficiencies of (30-2143)-fold higher than those of the commercial probes and low limit of detection (LOD ≤ 0.21 ng mL-1). The miniaturization of SPME sampling devices, as well as the low LOD of this work, endowed this method advantage of low consumption of bile samples (30 µL). Based on the proposed method, eight BAs in bile samples of pancreatic cancer patients and cholelithiasis patients were detected successfully. A distinct difference was found in the concentrations of four targeted BAs in bile samples from pancreatic cancer patients and cholelithiasis patients. This work provided a method for quantification of eight BAs in small volume human bile samples, and it could open up a perspective regarding the relationship between BA metabolism and the occurrence of diseases.

Targeting the biological activity and biosynthesis of hyperforin: a mini-review.

Hyperforin is a representative polycyclic polyprenylated acylphloroglucinols (PPAPs) that exerts a variety of pharmacological activities. The complete biosynthesis pathway of hyperforin has not been elucidated due to its complex structure and unclear genetic background of its source plants. This mini-review focuses on the bioactivity and biosynthesis of hyperforin. These analyses can provide useful insights into the biosynthesis investigations of hyperforin and other PPAPs with complex structures.

Identification of Candidate Genes for Twinning Births in Dezhou Donkeys by Detecting Signatures of Selection in Genomic Data.

Twinning trait in donkeys is an important manifestation of high fecundity, but few reports are available elucidating its genetic mechanism. To explore the genetic mechanism underlying the twin colt trait in Dezhou donkeys, DNA from 21 female Dezhou donkeys that had birthed single or twin colts were collected for whole-genome resequencing. FST, θπ and Tajima's D were used to detect the selective sweeps between single and twin colt fecundity in the Dezhou donkey groups. Another set of 20 female Dezhou donkeys with single or multiple follicles during estrus were selected to compare concentrations of reproductive hormone including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone (P4). Four candidate genes including ENO2, PTPN11, SOD2 and CD44 were identified in the present study. The CD44 gene had the highest FST value, and ENO2, PTPN11 and SOD2 were screened by two joint analyses (FST and θπ, θπ and Tajima's D). There was no significant difference in the LH, FSH and P4 levels between the two groups (p > 0.05); however, the serum E2 content in the multi-follicle group was significantly higher than that in the single-follicle group (p < 0.05). The identified candidate genes may provide new insights into the genetic mechanism of donkey prolificacy and may be useful targets for further research on high reproductive efficiency.

The value of radiomics based on dual-energy CT for differentiating benign from malignant solitary pulmonary nodules.

OBJECTIVE: To investigate the value of monochromatic dual-energy CT (DECT) images based on radiomics in differentiating benign from malignant solitary pulmonary nodules. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and informed consent was waived. Pathologically confirmed lung nodules smaller than 3 cm with integrated arterial phase and venous phase (AP and VP) gemstone spectral imaging were retrospectively identified. After extracting the radiomic features of each case, principal component analysis (PCA) was used for feature selection, and after training with the logistic regression method, three classification models (ModelAP, ModelVP and ModelCombination) were constructed. The performance was assessed by the area under the receiver operating curve (AUC), and the efficacy of the models was validated using an independent cohort. RESULTS: A total of 153 patients were included and divided into a training cohort (n = 107) and a validation cohort (n = 46). A total of 1130 radiomic features were extracted from each case. The PCA method selected 22, 25 and 35 principal components to construct the three models. The diagnostic accuracy of ModelAP, ModelVP and ModelCombination was 0.8043, 0.6739, and 0.7826 in the validation set, with AUCs of 0.8148 (95% CI 0.682-0.948), 0.7485 (95% CI 0.602-0.895), and 0.8772 (95% CI 0.780-0.974), respectively. The DeLong test showed that there were significant differences in the AUCs between ModelAP and ModelCombination (P = 0.0396) and between ModelVP and ModelCombination (P = 0.0465). However, the difference in AUCs between ModelAP and ModelVP was not significant (P = 0.5061). These results demonstrate that ModelCombination shows a better performance than the other models. Decision curve analysis proved the clinical utility of this model. CONCLUSIONS: We developed a radiomics model based on monochromatic DECT images to identify solitary pulmonary nodules. This model could serve as an effective tool for discriminating benign from malignant pulmonary nodules in patients. The combination of arterial phase and venous phase imaging could significantly improve the model performance.

Natural Flavonoids Derived From Fruits Are Potential Agents Against Atherosclerosis.

Atherosclerosis, as a chronic inflammatory response, is one of the main causes of cardiovascular diseases. Atherosclerosis is induced by endothelial cell dysfunction, migration and proliferation of smooth muscle cells, accumulation of foam cells and inflammatory response, resulting in plaque accumulation, narrowing and hardening of the artery wall, and ultimately leading to myocardial infarction or sudden death and other serious consequences. Flavonoid is a kind of natural polyphenol compound widely existing in fruits with various structures, mainly including flavonols, flavones, flavanones, flavanols, anthocyanins, isoflavones, and chalcone, etc. Because of its potential health benefits, it is now used in supplements, cosmetics and medicines, and researchers are increasingly paying attention to its role in atherosclerosis. In this paper, we will focus on several important nodes in the development of atherosclerotic disease, including endothelial cell dysfunction, smooth muscle cell migration and proliferation, foam cell accumulation and inflammatory response. At the same time, through the classification of flavonoids from fruits, the role and potential mechanism of flavonoids in atherosclerosis were reviewed, providing a certain direction for the development of fruit flavonoids in the treatment of atherosclerosis drugs.

Mineralogical Characterization of Gasification Ash with Different Particle Sizes from Lurgi Gasifier in the Coal-to-Synthetic Natural Gas Plant.

The Lurgi gasifier in China is one of the most suitable technologies to produce synthetic natural gas (SNG) from coal; however, a large amount of byproduct ash is discharged during the Lurgi gasification process, causing many environmental problems. Based on ash samples collected from a commercial Lurgi gasifier in a Chinese coal-to-SNG plant, this paper studied the mineral composition and microscopic appearance of gasification ash with different particle sizes. The typical minerals were identified and investigated by comparing them with the ash from a laboratory fixed-bed reactor. The results showed that the main high-temperature minerals in the Lurgi gasification ash with different particle sizes under the gasification condition of 4 MPa and 1100 °C were anorthite (CaAl2Si2O8), augite (CaFeSi2O6), hematite (Fe2O3), and gehlenite (Ca2Al2SiO7). As the particle size of the Lurgi gasification ash increased, the quartz content increased but the residual carbon content decreased. Additionally, the high-temperature minerals were more likely to agglomerate with fine particles of the ash. The FactSage modeling showed that calcium-bearing minerals were formed earlier than iron-bearing minerals. The high Fe2O3 content in ash hindered the transformation of calcium-bearing minerals into the high-melting-point mullite, resulting in a low ash flow temperature. Additionally, the fine ash had a relatively high content of calcium-bearing minerals which was not conducive to its utilization as an additive in cement and concrete.

The impact of watching real-time videos of flexible ureteroscopic lithotripsy on anxiety and depression in patients.

PURPOSE: This study examines the effect of intraoperative doctor-patient communication with real-time videos in flexible ureteroscopic lithotripsy on patients' anxiety and depression. METHODS: Patients with upper urinary tract calculi were randomised into four groups. Group A (n = 29) watched the real-time operation video, but did not accept the relevant explanation during the operation; Group B (n = 31) received an explanation about the operation process during the operation alone. Patients in Group C (n = 33) watched the real-time operation video and received an explanation about the operation process during the operation. Group D (n = 31) neither watched the operation video nor received an explanation about the operation process. The self-rated anxiety and depression scores of the patients were evaluated using the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) before and after the operation. RESULTS: The clinical and demographic profiles (average age, gender distribution, educational level, body mass index, stone size, the position of stones in each groups, the length of stayand the numbers of severe postoperative complications) of the for groups showed no preoperation difference (P > 0.05). The preoperative anxiety scores and the preoperative depression scores showed no significant difference in the four groups (P > 0.05). The scores of postoperative anxiety and depression in groups A (n = 29), B (n = 31), and C (n = 33) were significantly lower than those in Group D (n = 31), (P < 0. 05). Compared to groups A and B, the scores of anxiety and depression in Group C were significantly decreased (P < 0.05). CONCLUSION: During flexible ureteroscopic lithotripsy, doctor-patient communication combined with real-time video can significantly reduce patients' postoperative anxiety and depression, and contribute to their physical and mental health recovery.

Lymphangiogenesis contributes to exercise-induced physiological cardiac growth.

BACKGROUND: Promoting cardiac lymphangiogenesis exerts beneficial effects for the heart. Exercise can induce physiological cardiac growth with cardiomyocyte hypertrophy and increased proliferation markers in cardiomyocytes. However, it remains unclear whether and how lymphangiogenesis contributes to exercise-induced physiological cardiac growth. We aimed to investigate the role and mechanism of lymphangiogenesis in exercise-induced physiological cardiac growth. METHODS: Adult C57BL6/J mice were subjected to 3 weeks of swimming exercise to induce physiological cardiac growth. Oral treatment with vascular endothelial growth factor receptor 3 (VEGFR3) inhibitor SAR131675 was used to investigate whether cardiac lymphangiogenesis was required for exercise-induced physiological cardiac growth by VEGFR3 activation. Furthermore, human dermal lymphatic endothelial cell (LEC)-conditioned medium was collected to culture isolated neonatal rat cardiomyocytes to determine whether and how LECs could influence cardiomyocyte proliferation and hypertrophy. RESULTS: Swimming exercise induced physiological cardiac growth accompanied by a remarkable increase of cardiac lymphangiogenesis as evidenced by increased density of lymphatic vessel endothelial hyaluronic acid receptor 1-positive lymphatic vessels in the heart and upregulated LYVE-1 and Podoplanin expressions levels. VEGFR3 was upregulated in the exercised heart, while VEGFR3 inhibitor SAR131675 attenuated exercise-induced physiological cardiac growth as evidenced by blunted myocardial hypertrophy and reduced proliferation marker Ki67 in cardiomyocytes, which was correlated with reduced lymphatic vessel density and downregulated LYVE-1 and Podoplanin in the heart upon exercise. Furthermore, LEC-conditioned medium promoted both hypertrophy and proliferation of cardiomyocytes and contained higher levels of insulin-like growth factor-1 and the extracellular protein Reelin, while LEC-conditioned medium from LECs treated with SAR131675 blocked these effects. Functional rescue assays further demonstrated that protein kinase B (AKT) activation, as well as reduced CCAAT enhancer-binding protein beta (C/EBPß) and increased CBP/p300-interacting transactivators with E (glutamic acid)/D (aspartic acid)-rich-carboxylterminal domain 4 (CITED4), contributed to the promotive effect of LEC-conditioned medium on cardiomyocyte hypertrophy and proliferation. CONCLUSION: Our findings reveal that cardiac lymphangiogenesis is required for exercise-induced physiological cardiac growth by VEGFR3 activation, and they indicate that LEC-conditioned medium promotes both physiological hypertrophy and proliferation of cardiomyocytes through AKT activation and the C/EBPß-CITED4 axis. These results highlight the essential roles of cardiac lymphangiogenesis in exercise-induced physiological cardiac growth.

The diagnostic performance of radiomics-based MRI in predicting microvascular invasion in hepatocellular carcinoma: A meta-analysis.

Objective: The aim of this study was to assess the diagnostic performance of radiomics-based MRI in predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Method: The databases of PubMed, Cochrane library, Embase, Web of Science, Ovid MEDLINE, Springer, and Science Direct were searched for original studies from their inception to 20 August 2022. The quality of each study included was assessed according to the Quality Assessment of Diagnostic Accuracy Studies 2 and the radiomics quality score. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic (SROC) curve was plotted and the area under the curve (AUC) was calculated to evaluate the diagnostic accuracy. Sensitivity analysis and subgroup analysis were performed to explore the source of the heterogeneity. Deeks' test was used to assess publication bias. Results: A total of 15 studies involving 981 patients were included. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.79 (95%CI: 0.72-0.85), 0.81 (95%CI: 0.73-0.87), 4.1 (95%CI:2.9-5.9), 0.26 (95%CI: 0.19-0.35), 16 (95%CI: 9-28), and 0.87 (95%CI: 0.84-0.89), respectively. The results showed great heterogeneity among the included studies. Sensitivity analysis indicated that the results of this study were statistically reliable. The results of subgroup analysis showed that hepatocyte-specific contrast media (HSCM) had equivalent sensitivity and equivalent specificity compared to the other set. The least absolute shrinkage and selection operator method had high sensitivity and specificity than other methods, respectively. The investigated area of the region of interest had high specificity compared to the volume of interest. The imaging-to-surgery interval of 15 days had higher sensitivity and slightly low specificity than the others. Deeks' test indicates that there was no publication bias (P=0.71). Conclusion: Radiomics-based MRI has high accuracy in predicting MVI in HCC, and it can be considered as a non-invasive method for assessing MVI in HCC.

Ferroptosis-Inhibitory Difference between Chebulagic Acid and Chebulinic Acid Indicates Beneficial Role of HHDP.

The search for a safe and effective inhibitor of ferroptosis, a recently described cell death pathway, has attracted increasing interest from scientists. Two hydrolyzable tannins, chebulagic acid and chebulinic acid, were selected for the study. Their optimized conformations were calculated using computational chemistry at the B3LYP-D3(BJ)/6-31G and B3LYP-D3(BJ)/6-311 + G(d,p) levels. The results suggested that (1) chebulagic acid presented a chair conformation, while chebulinic acid presented a skew-boat conformation; (2) the formation of chebulagic acid requires 762.1729 kcal/mol more molecular energy than chebulinic acid; and (3) the 3,6-HHDP (hexahydroxydiphenoyl) moiety was shown to be in an (R)- absolute stereoconfiguration. Subsequently, the ferroptosis inhibition of both tannins was determined using a erastin-treated bone marrow-derived mesenchymal stem cells (bmMSCs) model and compared to that of ferrostatin-1 (Fer-1). The relative inhibitory levels decreased in the following order: Fer-1 > chebulagic acid > chebulinic acid, as also revealed by the in vitro antioxidant assays. The UHPLC-ESI-Q-TOF-MS analysis suggested that, when treated with 16-(2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxy free radicals, Fer-1 generated dimeric products, whereas the two acids did not. In conclusion, two hydrolyzable tannins, chebulagic acid and chebulinic acid, can act as natural ferroptosis inhibitors. Their ferroptosis inhibition is mediated by regular antioxidant pathways (ROS scavenging and iron chelation), rather than the redox-based catalytic recycling pathway exhibited by Fer-1. Through antioxidant pathways, the HHDP moiety in chebulagic acid enables ferroptosis-inhibitory action of hydrolyzable tannins.

Nucleated red blood cells participate in myocardial regeneration in the toad Bufo Gargarizan Gargarizan.

Heart regeneration is negligible in humans and mammals but remarkable in some ectotherms. Humans and mammals lack nucleated red blood cells (NRBCs), while ectotherms have sufficient NRBCs. This study used Bufo gargarizan gargarizan, a Chinese toad subspecies, as a model animal to verify our hypothesis that NRBCs participate in myocardial regeneration. NRBC infiltration into myocardium was seen in the healthy toad hearts. Heart needle-injury was used as an enlarged model of physiological cardiomyocyte loss. It recovered quickly and scarlessly. NRBC infiltration increased during the recovery. Transwell assay was done to in vitro explore effects of myocardial injury on NRBCs. In the transwell system, NRBCs could infiltrate into cardiac pieces and could transdifferentiate toward cardiomyocytes. Heart apex cautery caused approximately 5% of the ventricle to be injured to varying degrees. In the mildly to moderately injured regions, NRBC infiltration increased and myocardial regeneration started soon after the inflammatory response; the severely damaged region underwent inflammation, scarring, and vascularity before NRBC infiltration and myocardial regeneration, and recovered scarlessly in four months. NRBCs were seen in the newly formed myocardium. Enzyme-linked immunosorbent assay and Western blotting showed that the levels of tumor necrosis factor-α, interleukin- 1ß, 6, and11, cardiotrophin-1, vascular endothelial growth factor, erythropoietin, matrix metalloproteinase- 2 and 9 in the serum and/or cardiac tissues fluctuated in different patterns during the cardiac injury-regeneration. Cardiotrophin-1 could induce toad NRBC transdifferentiation toward cardiomyocytes in vitro. Taken together, the results suggest that the NRBC is a cell source for cardiomyocyte renewal/regeneration in the toad; cardiomyocyte loss triggers a series of biological processes, facilitating NRBC infiltration and transition to cardiomyocytes. This finding may guide a new direction for improving human myocardial regeneration.

Carbon dots based solid phase microextraction of 2-nitroaniline followed by fluorescence sensing for selective early screening and sensitive gas chromatography-mass spectrometry determination.

For decades, researches have been involving in improving and optimizing solid-phase microextraction (SPME) technique to fit the growing environmental analysis demand. But it is more significant now to introduce meaningful information into the analysis line instead of improving every step in SPME. Herein, we design a carbon dots (CDs) based SPME platform and report its unique application in selective early screening and sensitive detection of 2-nitroaniline. The fluorescence quenching state of the CDs fiber after extraction could be used to prejudge whether an environmental sample contains 2-nitroaniline exceeding the maximum permitted level (30 µg L-1) regulated by the Chinese Ministry of Environmental Protection or not. Photo-induced electron transfer (PET) is believed to be the primary quenching route that leads to electron transfer from the electron-rich CDs to the electron-deficient analyte. A preliminary in vivo study on Daphnia magna and a 2-nitroaniline assay in environmental water and biofluid samples suggested the safety and the excellent qualitative ability of the proposed platform. As a result, the innovative incorporation of fluorescence sensing and SPME not only achieves the information imbedding of environmental analysis system, but also combines the advantages of two techniques including early visual-screening, reusability (≥50 times), high specificity and excellent quantitative ability (detection limit: 0.011 µg L-1). We believe this study can open new avenues in the field of environmental toxicant monitoring.

2-Methoxy-6-acetyl-7-methyljuglone (MAM) induced programmed necrosis in glioblastoma by targeting NAD(P)H: Quinone oxidoreductase 1 (NQO1).

Glioblastoma (GBM) are the most malignant brain tumors in humans and have a very poor prognosis. Temozolomide (TMZ), the only chemotherapeutic drug for GBM treatment, induced apoptosis but frequently developed resistance. Non-apoptotic cell death offers an alternative strategy to fight cancers. Our previous studies showed that 2-methoxy-6-acetyl-7-methyljuglone (MAM), a natural product, induced necroptosis in lung and colon cancer cells. The current study is designed to investigate its therapeutic potentials for GBM with in vitro and in vivo models. The protein expression of NAD(P)H: quinone oxidoreductase 1 (NQO1) in human GBM specimens were detected by immunohistochemistry. Effect of MAM on NQO1 was measured by recombinant protein and cellular thermal shift assay. The roles of NQO1 activation, superoxide (O2-) generation, calcium (Ca2+) accumulation, and c-Jun N-terminal kinase (JNK1/2) activation in MAM-induced cell death in U87 and U251 glioma cells were investigated. The effect of MAM on tumor growth was tested with a U251 tumor xenograft zebrafish model. Results showed that the NQO1 expression is positively correlated with the degree of malignancy in GBM tissues. MAM could directly bind and activate NQO1. Furthermore, MAM treatment induced rapid O2- generation, cytosolic Ca2+ accumulation, and sustained JNK1/2 activation. In addition, MAM significantly suppressed tumor growth in the zebrafish model. In conclusion, MAM induced GBM cell death by triggering an O2-/Ca2+/JNK1/2 dependent programmed necrosis. NQO1 might be the potential target for MAM and mediated its anticancer effect. This non-apoptotic necrosis might have therapeutic potentials for GBM treatment.

Nesiritide protects endothelial function after balloon-induced trauma in the iliac artery in rabbits

To assess the effect of nesiritide on the endothelial function of iliac arteries following endothelia trauma. Right iliac artery trauma was created with a balloon catheter. Ten rabbits were treated with a 4-week subcutaneous injection of nesiritide at a fixed daily dose of 0.1mg/kg. Ten rabbits received daily normal saline injection. Plasma endothelin 1 (ET-1), nitric oxide (NO), and Von Willebrand Factor (vWF) were measured before and after the therapies. Tissue proliferating cell nuclear antigen (PCNA) was measured after the treatment. After the treatment, in the therapeutic group, the area under internal elastic membrane and the residual lumen area were higher than in the normal saline group (P <0.05). The plasma levels of ET-1 (91.6±6.8 vs 114.9±6.3 ng/L, P =0.001), vWF (134.6±10.8% vs 188.8±10.4%, P =0.001) and the ratio of PCNA positive expression (11.7±4.2% vs 36.2±11.4%, P =0.005) in the therapeutic group was lower than in the normal saline group, while the plasma levels of NO was higher (89.7±9.3 vs 43.5±5.3 µmol/L, P =0.001). Nesiritide inhibited remodeling of rabbit iliac artery following endothelial trauma. The inhibition of vascular remodeling may be related to the alleviated endothelial dysfunction and reduced expression of tissue proliferating cell nuclear antigen

Microwave-assisted solid-phase synthesis of highly fluorescent carbon nanoparticles and its application in intracellular pH sensing.

Fluorescent carbon nanoparticles (FCNPs) have been deeply researched and widely applied in recent years due to their good optics performance, chemical stability and biocompatibility. Herein, a green and rapid microwave-assisted solid-phase synthesis (solvent-free) approach was proposed for the fabrication of highly FCNPs in a very short period of time, 4 min. The as-prepared FCNPs can emit a blue emission with quantum yield of up to 63.2% in water solution and show yellow fluorescence in the solid state. The FCNPs also exhibit special solvent effect that the fluorescence emission can be adjusted by controlling the solvent ratio of ethanol and water. Most importantly, the FCNPs possess a narrow-range pH response. The probe responds linearly and rapidly to minor pH fluctuations within the range of 3.47-5.10 and the correlation coefficient is above 0.99. The proposed FCNPs also exhibit high photostability and reusability. As expected, the cell imaging and intracellular pH monitoring was achieved successfully in living SMMC 7721 hepatoma cells by this probe. The FCNPs is promising as a convenient and general fluorescent pH sensor for bioimaging applications.

Amine-functionalized MIL-53(Al)-coated stainless steel fiber for efficient solid-phase microextraction of synthetic musks and organochlorine pesticides in water samples.

The fiber coating is the key part of the solid-phase microextraction (SPME) technique, and it determines the sensitivity, selectivity, and repeatability of the analytical method. In this work, amine (NH2)-functionalized material of Institute Lavoisier (MIL)-53(Al) nanoparticles were successfully synthesized, characterized, and applied as the SPME fiber coating for efficient sample pretreatment owing to their unique structures and excellent adsorption properties. Under optimized conditions, the NH2-MIL-53(Al)-coated fiber showed good precision, low limits of detection (LODs) [0.025-0.83 ng L-1 for synthetic musks (SMs) and 0.051-0.97 ng L-1 for organochlorine pesticides (OCPs)], and good linearity. Experimental results showed that the NH2-MIL-53(Al) SPME coating was solvent resistant and thermostable. In addition, the extraction efficiencies of the NH2-MIL-53(Al) coating for SMs and OCPs were higher than those of commercially available SPME fiber coatings such as polydimethylsiloxane, polydimethylsiloxane-divinylbenzene, and polyacrylate. The reasons may be that the analytes are adsorbed on NH2-MIL-53(Al) primarily through π-π interactions, electron donor-electron acceptor interactions, and hydrogen bonds between the analytes and organic linkers of the material. Direct immersion (DI) SPME-gas chromatography-mass spectrometry methods based on NH2-MIL-53(Al) were successfully applied for the analysis of tap and river water samples. The recoveries were 80.3-115% for SMs and 77.4-117% for OCPs. These results indicate that the NH2-MIL-53(Al) coating may be a promising alternative to SPME coatings for the enrichment of SMs and OCPs.