Exosome-transported circ_0061407 and circ_0008103 play a tumour-repressive role and show diagnostic value in non-small-cell lung cancer.

BACKGROUND: Circular RNAs (circRNAs), one of the major contents of exosomes, have been shown to participate in the occurrence and progression of cancers. The role and the diagnostic potential of exosome-transported circRNAs in non-small-cell lung cancer (NSCLC) remain largely unknown. METHODS: The NSCLC-associated exosomal circ_0061407 and circ_0008103 were screened by circRNA microarray. The role of circ_0061407 and circ_0008103 in NSCLC was examined in vitro and in vivo. The encapsulation of the two circRNAs into exosomes and the transport to recipient cells were observed by confocal microscopy. The effects of exosome-transported circ_0061407 and circ_0008103 on recipient cells were investigated using a co-culture device. Bioinformatics analyses were performed to predict the mechanisms by which circ_0061407 and circ_0008103 affected NSCLC. The quantitative polymerase chain reaction was used to quantify the exosome-containing circ_0061407 and circ_0008103 in the serum samples of healthy, pneumonia, benign lung tumours, and NSCLC. The diagnostic efficacy was evaluated using receiver operating characteristic curves. RESULTS: The levels of circ_0061407 and circ_0008103 within exosomes were down-regulated in the serum of patients with NSCLC. The up-regulation of circ_0061407 and circ_0008103 inhibited the proliferation, migration/invasion, cloning formation of NSCLC cells in vitro and inhibited lung tumour growth in vivo. Circ_0061407 and circ_0008103 were observed to be packaged in exosomes and transported to recipient cells, where they inhibited the proliferation, migration/invasion, and cloning formation abilities of the recipient cells. Moreover, circ_0061407 and circ_0008103 might be involved in the progression of NSCLC by interacting with microRNAs and proteins. Additionally, lower serum exosomal circ_0061407 and circ_0008103 levels were associated with advanced pathological staging and distant metastasis. CONCLUSIONS: This study identified two novel exosome-transported circRNAs (circ_0061407 and circ_0008103) associated with NSCLC. These findings may provide additional insights into the development of NSCLC and potential diagnostic biomarkers for NSCLC.

Isolation and antioxidant activity of peptides from Chinese hairy tofu.

Hairy tofu is a famous Chinese snack that is made from soybeans and rich in various nutrients. In order to further explore the antioxidant peptides of hairy tofu hydrolysates, seven proteases were used to hydrolyze hairy tofu. The results of in vitro radical scavenging activity showed that hairy tofu hydrolysates obtained by pancreatin exhibited the highest antioxidant activity. After Sephadex G-25 gel filtration and reversed-phase high-performance liquid chromatography (RP-HPLC), 97 peptides were identified in the most antioxidant fraction using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Among them, nine peptides were synthesized and their antioxidant activities were assessed using a H2O2-induced oxidative 293T cell model. Finally, four peptides (QCESHK, LAWNEGR, NLQGENEWDQK, and FTEMWR) at concentrations of < 50 µg/ml significantly decreased the malondialdehyde content compared with the model group, displaying in vivo antioxidant activity and low cytotoxicity. Overall, this research provided the choice of using hairy tofu peptides as antioxidant products in the pharmaceutical and food industries.

Ionizing radiation induces neurotoxicity in Xenopus laevis embryos through neuroactive ligand-receptor interaction pathway.

Ionizing radiation (IR) poses a significant threat to both the natural environment and biological health. Exposure to specific doses of ionizing radiation early in an organism's development can lead to developmental toxicity, particularly neurotoxicity. Through experimentation with Xenopus laevis (X. laevis), we examined the effects of radiation on early developmental stage. Our findings revealed that radiation led to developmental abnormalities and mortality in X. laevis embryos in a dose-dependent manner, disrupting redox homeostasis and inducing cell apoptosis. Additionally, radiation caused neurotoxic effects, resulting in abnormal behavior and neuron damage in the embryos. Further investigation into the underlying mechanisms of radiation-induced neurotoxicity indicated the potential involvement of the neuroactive ligand-receptor interaction pathway, which was supported by RNA-Seq analysis. Validation of gene expression associated with this pathway and analysis of neurotransmitter levels confirmed our hypothesis. In addition, we further validated the important role of this signaling pathway in radiation-induced neurotoxicity through edaravone rescue experiments. This research establishes a valuable model for radiation damage studying and provides some insight into radiation-induced neurotoxicity mechanisms.

Uric acid reference values for children and adolescents should be stratified by pubertal stage.

BACKGROUND AND AIM: To establish reference values for hyperuricemia (HUA) in children and adolescents. METHODS AND RESULTS: The study enrolled 4807 students from "The Evaluation and Monitoring on School-based Nutrition and Growth in Shenzhen study." Utilizing quantile regression, associations between age, body mass index (BMI), pubertal stage, and serum uric acid (SUA) were examined, alongside the relationship between SUA and cardiovascular disease (CVD) risk factors. Reference values for SUA were explored using receiver operating characteristic analysis, considering sex and pubertal stage. The prevalence of HUA was 34.3 % for boys and 29 % for girls (using the adult HUA diagnostic criteria: >420 µmol/L for males, >360 µmol/L for females), increasing with higher BMI, age, and pubertal stage. Pubertal stage had the largest influence on SUA in boys, while nutritional status was the most significant factor affecting SUA in girls. Adjusting for age and pubertal stage, higher SUA levels correlated with an increased risk of CVD risk factors. Proposed reference values included >360 µmol/L for girls ages 6-17 years and prepubertal boys. For pubertal boys, reference values varied based on age: >392 µmol/L for ages 9-11 in early-middle puberty, >429 µmol/L for ages 12-14 in early-middle puberty, >478 µmol/L for ages 12-14 in late puberty, and >505 µmol/L for ages 15-17 in late puberty. CONCLUSIONS: Stratifying HUA reference values by pubertal stage, particularly for boys, is crucial. Long-term follow-up of individuals with high SUA levels may aid in refining SUA reference values.

Thiostrepton suppresses triple-negative breast cancer through downregulating c-FLIP/SMAD2/3 signaling pathway.

Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis of breast cancer. Thiostrepton exerts anti-tumor activities against several cancers including TNBC. Herein we discussed the new molecular mechanisms of thiostrepton in TNBC. Thiostrepton inhibited MDA-MB-231 cell viability, accompanied by a decrease of c-FLIP and p-SMAD2/3. c-FLIP overexpression reduced the sensitivity of MDA-MB-231 cells to thiostrepton, while SMAD2/3 knockdown increased the sensitivity of MDA-MB-231 cells to thiostrepton. Moreover, c-FLIP overexpression significantly increased the expression and phosphorylation of SMAD2/3 proteins and vice versa. In conclusion, our study reveals c-FLIP/SMAD2/3 signaling pathway as a novel mechanism of antitumor activity of thiostrepton.

Chromomycins from soil-derived Streptomyces sp. inhibit the growth of human non-small cell lung cancer cells by targeting c-FLIP.

Three chromomycin derivatives, chromomycins A3 (1, CA3), A5 (2, CA5), and monodeacetylchromomycin A3 (3, MDA-CA3), were identified from the soil-derived Streptomyces sp. CGMCC 26516. A reinvestigation of the structure of CA5 is reported, of which the absolute configuration was unambiguously determined for the first time to be identical with that of CA3 based on nuclear magnetic resonance (NMR) data analysis as well as NMR and electronic circular dichroism calculations. Compounds 1-3 showed potent cytotoxicity against the non-small-cell lung cancer (NSCLC) cells (A549, H460, H157-c-FLIP, and H157-LacZ) and down-regulated the protein expression of c-FLIP in A549 cells. The IC50 values of chromomycins in H157-c-FLIP were higher than that in H157-LacZ. Furthermore, si-c-FLIP promoted anti-proliferation effect of chromomycins in NSCLC cells. In nude mice xenograft model, 1 and 2 both showed more potent inhibition on the growth of H157-lacZ xenografts than that of H157-c-FLIP xenografts. These results verify that c-FLIP mediates the anticancer effects of chromomycins in NSCLC.

Short-axis PET image quality improvement based on a uEXPLORER total-body PET system through deep learning.

PURPOSE: The axial field of view (AFOV) of a positron emission tomography (PET) scanner greatly affects the quality of PET images. Although a total-body PET scanner (uEXPLORER) with a large AFOV is more sensitive, it is more expensive and difficult to widely use. Therefore, we attempt to utilize high-quality images generated by uEXPLORER to optimize the quality of images from short-axis PET scanners through deep learning technology while controlling costs. METHODS: The experiments were conducted using PET images of three anatomical locations (brain, lung, and abdomen) from 335 patients. To simulate PET images from different axes, two protocols were used to obtain PET image pairs (each patient was scanned once). For low-quality PET (LQ-PET) images with a 320-mm AFOV, we applied a 300-mm FOV for brain reconstruction and a 500-mm FOV for lung and abdomen reconstruction. For high-quality PET (HQ-PET) images, we applied a 1940-mm AFOV during the reconstruction process. A 3D Unet was utilized to learn the mapping relationship between LQ-PET and HQ-PET images. In addition, the peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) were employed to evaluate the model performance. Furthermore, two nuclear medicine doctors evaluated the image quality based on clinical readings. RESULTS: The generated PET images of the brain, lung, and abdomen were quantitatively and qualitatively compatible with the HQ-PET images. In particular, our method achieved PSNR values of 35.41 ± 5.45 dB (p < 0.05), 33.77 ± 6.18 dB (p < 0.05), and 38.58 ± 7.28 dB (p < 0.05) for the three beds. The overall mean SSIM was greater than 0.94 for all patients who underwent testing. Moreover, the total subjective quality levels of the generated PET images for three beds were 3.74 ± 0.74, 3.69 ± 0.81, and 3.42 ± 0.99 (the highest possible score was 5, and the minimum score was 1) from two experienced nuclear medicine experts. Additionally, we evaluated the distribution of quantitative standard uptake values (SUV) in the region of interest (ROI). Both the SUV distribution and the peaks of the profile show that our results are consistent with the HQ-PET images, proving the superiority of our approach. CONCLUSION: The findings demonstrate the potential of the proposed technique for improving the image quality of a PET scanner with a 320 mm or even shorter AFOV. Furthermore, this study explored the potential of utilizing uEXPLORER to achieve improved short-axis PET image quality at a limited economic cost, and computer-aided diagnosis systems that are related can help patients and radiologists.

Alkylamine-Grafted Molybdenum Disulfide Nanosheets for Enhanced Dispersion Stability and Lubricity Properties.

The unique structure and ultralow interlayer shear strength give molybdenum disulfide (MoS2) materials a broad prospect for energy savings, economic benefits, and extended operating life of lubrication systems. Herein, we prepared an effective integration strategy to prepare novel small-sized and chemically grafted MoS2 to solve the problems of poor dispersibility and easy agglomeration of MoS2. The MoS2 powder was stripped and oxidized to generate active centers using acid oxidation and high-speed ultrasonic crushing to obtain two different types of alkylamine chemically, covalently grafted, oxidized MoS2 nanosheets as lubricant additives to achieve friction reduction and antiwear. The chemical changes and structural characteristics of different types of alkylamine molecules upon covalent interaction with oxidized MoS2 were investigated in detail by FTIR, XPS, TGA, XRD, and TEM analyses. The results showed that the alkylamine-grafted MoS2 oxide nanosheets had good dispersion in 15# industrial white oil, and friction experiments confirmed that the alkylamine-grafted MoS2 oxide (MoS2-O-OLA) nanosheets exhibited better friction and wear resistance such that, compared with pure 15# industrial white oil, the 0.02 wt % MoS2-O-OLA nanosheets could significantly reduce friction (36.2%) and wear (22.4%). The field-emission scanning electron microscopy (FESEM) and EDS analyses of the wear surface showed that MoS2-O-OLA nanosheets play an important role in improving tribological properties by generating interlayer slippage at the steel ball contact interface, thereby forming surface protection and a uniform oil film.

The Composite Immune Risk Score predicts overall survival after allogeneic hematopoietic stem cell transplantation: A retrospective analysis of 1838 cases.

There has been little consensus on how to quantitatively assess immune reconstitution after hematopoietic stem cell transplantation (HSCT) as part of the standard of care. We retrospectively analyzed 11 150 post-transplant immune profiles of 1945 patients who underwent HSCT between 2012 and 2020. 1838 (94.5%) of the cases were allogeneic HSCT. Using the training set of patients (n = 729), we identified a composite immune signature (integrating neutrophil, total lymphocyte, natural killer, total T, CD4+ T, and B cell counts in the peripheral blood) during days 91-180 after allogeneic HSCT that was predictive of early mortality and moreover simplified it into a formula for a Composite Immune Risk Score. When we verified the Composite Immune Risk Score in the validation (n = 284) and test (n = 391) sets of patients, a high score value was found to be associated with hazard ratios (HR) of 3.64 (95% C.I. 1.55-8.51; p = .0014) and 2.44 (95% C.I., 1.22-4.87; p = .0087), respectively, for early mortality. In multivariate analysis, a high Composite Immune Risk Score during days 91-180 remained an independent risk factor for early mortality after allogeneic HSCT (HR, 1.80; 95% C.I., 1.28-2.55; p = .00085). In conclusion, the Composite Immune Risk Score is easy to compute and could identify the high-risk patients of allogeneic HSCT who require targeted effort for prevention and control of infection.

Combined assisted bone age assessment and adult height prediction methods in Chinese girls with early puberty: analysis of three artificial intelligence systems.

BACKGROUND: The applicability and accuracy of artificial intelligence (AI)-assisted bone age assessment and adult height prediction methods in girls with early puberty are unknown. OBJECTIVE: To analyze the performance of AI-assisted bone age assessment methods by comparing the corresponding methods for predicted adult height with actual adult height. MATERIALS AND METHODS: This retrospective review included 726 girls with early puberty, 87 of whom had reached adult height at last follow-up. Bone age was evaluated using the Greulich-Pyle (GP), Tanner-Whitehouse (TW3-RUS) and China 05 RUS-CHN (RUS-CHN) methods. Predicted adult height was calculated using the China 05 (CH05), TW3 and Bayley-Pinneau (BP) methods. RESULTS: We analyzed 1,663 left-hand radiographs, including 155 from girls who had reached adult height. In the 6-8- and 9-11-years age groups, bone age differences were smaller than those in the 12-14-years group; however, the differences between predicted adult height and actual adult height were larger than those in the 12-14-years group. TW3 overestimated adult height by 0.4±2.8 cm, while CH05 and BP significantly underestimated adult height by 2.9±3.6 cm and 1.3±3.8 cm, respectively. TW3 yielded the highest proportion of predicted adult height within ±5 cm of actual adult height (92.9%), with the highest correlation between predicted and actual adult heights. CONCLUSION: The differences in measured bone ages increased with increasing bone age. However, the corresponding method for predicting adult height was more accurate when the bone age was older. TW3 might be more suitable than CH05 and BP for predicting adult height in girls with early puberty. Methods for predicting adult height should be optimized for populations of the same ethnicity and disease.

[Inhibitory effect and molecular mechanism of sinomenine on human hepatocellular carcinoma HepG2 and SK-HEP-1 cells].

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.

[Morin induces autophagy and apoptosis in hepatocellular carcinoma cells through Akt/mTOR/STAT3 pathway].

This study investigated the effect and mechanism of morin in inducing autophagy and apoptosis in hepatocellular carcinoma cells through the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription protein 3(STAT3) pathway. Human hepatocellular carcinoma SK-HEP-1 cells were stimulated with different concentrations of morin(0, 50, 100, 125, 200, and 250 µmol·L~(-1)). The effect of morin on the viability of SK-HEP-1 cells was detected by Cell Counting Kit-8(CCK-8). The effect of morin on the proliferation and apoptosis of SK-HEP-1 cells was investigated using colony formation assay, flow cytometry, and BeyoClick~(TM) EdU-488 with different concentrations of morin(0, 125, and 250 µmol·L~(-1)). The changes in the autophagy level of cells treated with morin were examined by transmission electron microscopy and autophagy inhibitors. The impact of morin on the expression levels of proteins related to the Akt/mTOR/STAT3 pathway was verified by Western blot. Compared with the control group, the morin groups showed decreased viability of SK-HEP-1 cells in a time-and concentration-dependent manner, increased number of apoptotic cells, up-regulated expression level of apoptosis marker PARP, up-regulated phosphorylation level of apoptosis-regulating protein H2AX, decreased number of positive cells and the colony formation rate, an upward trend of expression levels of autophagy-related proteins LC3-Ⅱ, Atg5, and Atg7, and decreased phosphorylation levels of Akt, mTOR, and STAT3. These results suggest that morin can promote apoptosis, inhibit proliferation, and induce autophagy in hepatocellular carcinoma cells, and its mechanism of action may be related to the Akt/mTOR/STAT3 pathway.

Thymidine Kinase 1 Mediates the Synergistic Antitumor Activity of Ubenimex and Celecoxib via Regulation of Cell Cycle in Colorectal Cancer.

Colorectal cancer (CRC) is a common clinical malignant tumor of the digestive system that seriously affects the health and life of patients. Because it is difficult to cure CRC, the strategy of drug combination is often used in clinical therapy. This study mainly revealed that ubenimex and/or celecoxib exerted anti-colon cancer effects in vitro and in vivo, and the efficacy was significantly enhanced when the two drugs were combined. The combination of the two drugs induced significantly stronger cell-cycle arrest than did the single drug, and also enhanced the antitumor efficacy of 5-fluorouracil and its derivatives. At the same time, the expression of thymidine kinase 1 (TK1) protein was decreased through regulating the level of TK1 mRNA treated with celecoxib and/or ubenimex, but the combination drugs exhibited much more reduction of TK1 mRNA and protein as compared with the single agent alone. TK1 may be the molecular target of the combination of two drugs to exert the anti-colorectal cancer effect. In summary, this research demonstrates that celecoxib combined with ubenimex inhibits the development of colorectal cancer in vitro and in vivo, making them a viable combination regimen. SIGNIFICANCE STATEMENT: In this study, our data reveal the great potential of celecoxib combined with ubenimex in the treatment of colorectal cancer, providing new ideas for clinical antitumor drug regimens and theoretical reference for drug development.

Proof-of-concept study of the virtual optical scale bar by the pulse-to-pulse interferometry.

The optical scale bar with calibrated or measured internal point-to-point length has many applications in coordinate measurements. In this paper, the virtual optical scale bar with two retroreflectors is constructed by the absolute distance measurement based on pulse-to-pulse interferometry. The temporal and dispersive coherence could be utilized to determine the adjustable internal length of multiple pulse-to-pulse intervals with high precision. The proposed scheme was combined with a pellicle beamsplitter to minimize systematic error. The influence of its thickness on precision is also discussed and calibrated in detail. Besides, a femtosecond mode-locked pulse laser with 100-MHz repetition rates was employed in our system to develop an optical scale bar and verify the feasibility of the proposed method. The sub-micron precision could be realized by temporal coherence with a piezo-driven stage or a simplified non-polarized scheme of dispersed coherence. It shows that this method could achieve a flexible and high-precision virtual optical scale bar for further practical applications.

c-FLIP promotes drug resistance in non-small-cell lung cancer cells via upregulating FoxM1 expression.

The forkhead box M1 (FoxM1) protein, a transcription factor, plays critical roles in regulating tumor growth and drug resistance, while cellular FLICE-inhibitory protein (c-FLIP), an anti-apoptotic regulator, is involved in the ubiquitin-proteasome pathway. In this study, we investigated the effects of c-FLIP on the expression and ubiquitination levels of FoxM1 along with drug susceptibility in non-small-cell lung cancer (NSCLC) cells. We first showed that the expression levels of FoxM1 and c-FLIP were increased and positively correlated (R2 = 0.1106, P < 0.0001) in 90 NSCLC samples. The survival data from prognostic analysis demonstrated that high expression of c-FLIP and/or FoxM1 was related to poor prognosis in NSCLC patients and that the combination of FoxM1 and c-FLIP could be a more precise prognostic biomarker than either alone. Then, we explored the functions of c-FLIP/FoxM1 in drug resistance in NSCLC cell lines and a xenograft mouse model in vivo. We showed that c-FLIP stabilized FoxM1 by inhibiting its ubiquitination, thus upregulated the expression of FoxM1 at post-transcriptional level. In addition, a positive feedback loop composed of FoxM1, ß-catenin and p65 also participated in c-FLIP-FoxM1 axis. We revealed that c-FLIP promoted the resistance of NSCLC cells to thiostrepton and osimertinib by upregulating FoxM1. Taken together, these results reveal a new mechanism by which c-FLIP regulates FoxM1 and the function of this interaction in the development of thiostrepton and osimertinib resistance. This study provides experimental evidence for the potential therapeutic benefit of targeting the c-FLIP-FoxM1 axis for lung cancer treatment.

Knockout of zebrafish colony-stimulating factor 1 receptor by CRISPR/Cas9 affects metabolism and locomotion capacity.

Colony-stimulating factor 1 receptor (CSF1R) is a tyrosine kinase receptor and a key regulator of proliferation, differentiation, migration, and colonization in macrophage lineage cells. CSF1R was found to be involved in the pathogenesis of immune disorders, hematopoietic diseases, tissue damage, tumor growth and metastasis, and so on. Hence, understanding the role of CSF1R is important. CSF1R is highly conserved among vertebrates. In zebrafish, it is encoded by the colony-stimulating factor 1 receptor a (csf1ra) gene. In this study, a csf1ra-/- zebrafish mutant line was generated using clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (CRISPR/Cas9) technology. csf1ra-/- larvae lacked the yellow cast on their heads and over their flanks, while adult mutants had poorly formed stripes. RNA-sequence analysis revealed that genes related to bile acid secretion, fat digestion and absorption, and pancreatic secretion were differentially expressed in csf1ra-/- mutants, which led to fatty changes in the liver. In addition, genes related to locomotion were also significantly changed, with the more active movement observed in csf1ra-/- larvae. Our study demonstrated that csf1ra participates in the metabolic process and behavior. This study provides new insights into csf1ra function during zebrafish development.

[Effect of Danhong Injection on platelet metabolites based on metabonomics technology].

The effect of Danhong Injection on the endogenous metabolites of rabbit platelets was analyzed by the liquid chromatography-mass spectrometry( LC-MS) based metabonomic approach. Anti-platelet aggregation was detected after Danhong Injection treatment and the changes of platelet metabolites were analyzed by metabonomics. Principal component analysis( PCA) and partial least squares discriminant analysis( PLS-DA) were performed to investigate the effect of Danhong Injection on endogenous metabolites of platelets,characterize the biomarkers,and explore the relevant pathways and the underlying mechanism. As demonstrated by the pharmacodynamic results,Danhong Injection of different doses and concentrations antagonized platelet aggregation in a dose-and concentration-dependent manner. In contrast to the control group,25 differential metabolites such as nicotinic acid,nicotinic acid riboside,and hypoxanthine were screened out after platelets were treated by Danhong Injection. These metabolites,serving as important biomarkers,were mainly enriched in the nicotinic acid-niacinamide metabolic pathway and purine metabolic pathway. This study explored the therapeutic mechanism of Danhong Injection from a microscopic perspective by metabonomics,which is expected to provide a new idea for the investigation of platelet-related mechanisms.

[Analysis and comparison of metabolic processes of salvianolic acid A and salvianolic acid B in rats based on UHPLC-LTQ-Orbitrap MS technology].

The metabolites of salvianolic acid A and salvianolic acid B in rats were analyzed and compared by ultra-high-perfor-mance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS). After the rats were administrated by gavage, plasma at different time points and urine within 24 hours were collected to be treated by solid phase extraction(SPE), then they were gradient eluted by Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) and 0.1% formic acid solution(A)-acetonitrile(B) mobile phase system, and finally all biological samples of rats were analyzed under negative ion scanning mode. By obtaining the accurate relative molecular mass and multi-level mass spectrometry information of metabolites, combined with the characteristic cleavage law of the reference standard and literature reports, a total of 30 metabolites, including salvianolic acid A and B, were identified. Among them, there were 24 metabolites derived from salvianolic acid A, with the main metabolic pathways including ester bond cleavage, dehydroxylation, decarboxylation, hydrogenation, methylation, hydroxylation, sulfonation, glucuronidation, and their multiple reactions. There were 15 metabolites of salvianolic acid B, and the main biotransformation pathways were five-membered ring cracking, ester bond cleavage, decarboxylation, dehydroxylation, hydrogenation, methylation, sulfonation, glucuronidation, and their compound reactions. In this study, the cross-metabolic profile of salvianolic acid A and B was elucidated completely, which would provide reference for further studies on the basis of pharmacodynamic substances and the exploration of pharmacological mechanism.

Precision improvement in frequency scanning interferometry based on suppression of the magnification effect.

Frequency scanning interferometry (FSI) is a promising technique for absolute distance measurement and has been demonstrated in many industrial applications. However, in practice, the measurement precision is limited and sensitive to the variations of the measured distance while sweeping the optical frequency of the laser. The induced errors would be amplified by hundreds of times due to the magnification effect. In this paper, an incremental interferometer was established on the basic scheme of the FSI system for monitoring the variations of distance. The compensation could be achieved by multiplying the heterodyne signals from monitor and measurement interferometer without complex and time-costing data processing. The system performance has been verified by experiments for different kinds of vibrating targets. Finally, after compensation by suppression of the magnification effects, a measurement precision of 4.26 µm has been achieved in a range of 10 m.

CARM1 contributes to skeletal muscle wasting by mediating FoxO3 activity and promoting myofiber autophagy.

Coactivator-associated arginine methyltransferase 1 (CARM1) is involved in a variety of biological processes in different cell types and disease conditions, including myogenesis. However, the specific function of CARM1 in skeletal muscle wasting under pathologic conditions remains unclear. Here, we identify CARM1 as a novel participant in muscular atrophy. Increases in CARM1 protein levels correlated positively with the loss of muscle mass upon denervation in mice. Notably, the knockdown of CARM1 represses the progression of muscle wasting and the expression of the atrophy-related genes Atrogin-1 and MuRF1 in vivo and in vitro. With respect to the underlying mechanism, we show that CARM1 interacts with and asymmetrically dimethylates FoxO3 (a specific transcription factor that controls atrophy-related gene expression). This methylation modification by CARM1 is required for FoxO3-dependent transcription. Accordingly, a CARM1 methyltransferase inhibitor also restrains the expression of Atrogin-1 and MuRF1 and myotube atrophy. Furthermore, CARM1 knockdown induces a remarkable myofiber autophagic deficit during the atrophy process. Altogether, our study identifies a crucial regulator of skeletal muscle atrophy and suggests that CARM1 is a potential target for the prevention of muscle atrophy.