Salidroside inhibits the ferroptosis to alleviate lung ischemia reperfusion injury via the JAK2/STAT3 signalling pathway.

OBJECTIVE: The present study aims to investigate the protective potential of salidroside in both lung ischemia/reperfusion injury (LIRI) mice model and cell hypoxia/reoxygenation (H/R)model and the involvement of ferroptosis and JAK2/STAT3 pathway. MATERIALS AND METHODS: After we established the IR-induced lung injury model in mice, we administered salidroside and the ferroptosis inhibitor, ferrostatin-1, then assessed the lung tissue injury, ferroptosis (levels of reactive oxygen species level, malondialdehyde and glutathione), and inflammation in lung tissues. The levels of ferroptosis-related proteins (glutathione peroxidase 4, fibroblast-specific protein 1, solute carrier family 1 member 5 and glutaminase 2) in the lung tissue were measured with Western blotting. Next, BEAS-2B cells were used to establish an H/R cell model and treated with salidroside or ferrostatin-1 before the cell viability and the levels of lactate dehydrogenase (LDH), inflammatory factor, ferroptosis-related proteins were measured. The activation of the JAK2/STAT3 signaling pathway was measured with Western blotting, then its role was confirmed with STAT3 knockdown. RESULTS: Remarkably, salidroside was found to alleviate ferroptosis, inflammation, and lung injury in LIRI mice and the cell injury in H/R cell model. Severe ferroptosis were observed in LIRI mice models and H/R-induced BEAS-2B cells, which was alleviated by salidroside. Furthermore, salidroside could inhibit JAK2/STAT3 activation induced by LIRI. STAT3 knockdown could enhance the effect of salidroside treatment on H/R-induced cell damage and ferroptosis in vitro. CONCLUSIONS: Salidroside inhibits ferroptosis to alleviate lung ischemia reperfusion injury via the JAK2/STAT3 signaling pathway.

Preparation of COF-coated nickel foam adsorbents for dispersive solid-phase extraction of 16 polycyclic aromatic hydrocarbons from Chinese herbal medicines.

Covalent organic framework coated nickel foam (NF@COF) was prepared as a sorbent for the dispersive solid phase extraction (DSPE) of polycyclic aromatic hydrocarbons (PAHs) from Chinese herbal medicines (CHMs) prior to their determination by gas chromatography-mass spectrometry (GC-MS). The structure and morphology of the as-synthesized NF@COF were characterized by different techniques. Various key parameters affecting the performance of the DSPE method, including the amount of sorbent, desorption solvent, desorption volume and time, extraction time, and sample volume, were investigated. Under the optimized conditions, NF@COF combined with GC-MS was successfully applied to the determination of 16 PAHs in CHMs. The method showed wide linearity (20-2000 ng mL-1), low limits of determination (0.3-2.7 ng mL-1), and high recoveries (78.0-124%). These results revealed that NF@COF has the potential for efficient extraction of PAHs from complex samples.

Determination of polycyclic aromatic hydrocarbons in Chinese herbal medicines by gas chromatography-mass spectrometry with graphene-functionalized nickel foam.

Graphene-functionalized nickel foam (NF) sorbent materials were prepared and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Thermogravimetric analysis. For the separation and detection of polycyclic aromatic hydrocarbons (PAHs) in five Chinese medicine samples, namely dandelion, fructus aurantii, peppermint, mulberry leaf and embryo chrysanthemum, a method combining dispersive micro-solid phase extraction and gas chromatography-mass spectrometry (GC-MS) was developed. Four conditions affecting the extraction efficiency, such as the type of desorption solvent, the amount of sorbent, the extraction time and the volume of water sample, were optimized. The results of the methodological validation showed that NF@SiO2@G was able to adsorb PAHs well and with good reproducibility. All analytes showed good linearity in the concentration range of 20-2000 ng/mL with coefficient of determination R2≥0.9956. The limit of detection was 0.98-13.34 ng/mL, and the limit of quantification ranged from 3.25 to 44.47 ng/mL. Both the intra-day and inter-day precision were lower than 15.46%, and the spiked recoveries were in the range of 75.5-118.4%. The total contents of the 16 PAHs contained in these five Chinese herbal medicines (CHMs) were varied from 450 to 1557 µg/kg. The results indicated that the graphene-functionalized NF sorbent combined with GC-MS can effectively detect PAHs in CHMs.

Interaction Mechanism of Thermal and Mechanical Field in KDP Fly-Cutting Process.

As an important nonlinear optical material, potassium dihydrogen phosphate (KDP) crystal is used in high-power laser beams as the core element of inertial confinement fusion. It is the most general method of single point diamond fly-cutting (SPDF) to produce high precision and crack-free KDP surfaces. Nevertheless, the cutting mechanism of such material remains unclear, and therefore needs further analysis. Firstly, the stress field, cutting force and cutting temperature under different working conditions are calculated by a KDP crystal cutting simulation model. Then, the rules and the cause of change and interaction mechanisms of force and temperature are analyzed by comparing the measurement experiments with simulations. Furthermore, the causes of chip formation and micro-cracks on the machined surface are analyzed based on thermo-mechanical coupling and chip morphology. The conclusion can be deduced: Although the temperature has not reached the phase transition temperature during the finishing process, under high cutting speeds and large unformed chip thickness, such as semi-finishing and roughing, the temperature can reach up to 180 °C or higher, and KDP crystals are very likely to phase transition-chip morphology also verifies this phenomenon.

Serum Protein N-Glycosylation Signatures of Neuroblastoma.

BACKGROUND: Neuroblastoma is the most common extracranial childhood solid tumor which accounts for 10% of the malignancies and 15% of the cancer fatalities in children. N-glycosylation is one of the most frequent post-translation protein modification playing a vital role in numerous cancers. N-glycosylation changes in neuroblastoma patient serum have not been studied in existing reports. The comprehensive analyses of serum N-glycomics in neuroblastoma can provide useful information of potential disease biomarkers and new insights of the pathophysiology in neuroblastoma. METHODS: The total serum protein N-glycosylation was analyzed in 33 neuroblastoma patients and 40 age- and sex-matched non-malignant controls. N-glycans were enzymatically released, derivatized to discriminate linkage-specific sialic acid, purified by HILIC-SPE, and identified by MALDI-TOF-MS. Peak areas were acquired by the software of MALDI-MS sample acquisition, processed and analyzed by the software of Progenesis MALDI. RESULTS: Three glyco-subclasses and six individual N-glycans were significantly changed in neuroblastoma patients compared with controls. The decreased levels of high mannose N-glycans, hybrid N-glycans, and increased levels of α2,3-sialylated N-glycans, multi-branched sialylated N-glycans were observed in neuroblastoma patients. what is more, a glycan panel combining those six individual N-glycans showed a strong discrimination performance, with an AUC value of 0.8477. CONCLUSIONS: This study provides new insights into N-glycosylation characteristics in neuroblastoma patient serum. The analyses of total serum protein N-glycosylation could discriminate neuroblastoma patients from non-malignant controls. The alterations of the N-glycomics may play a suggestive role for neuroblastoma diagnosis and advance our understanding of the pathophysiology in neuroblastoma.

Transcriptional regulation of human abraxas brother protein 1 expression by yin yang 1.

Abraxas brother protein 1 (ABRO1) is a subunit of the deubiquitinating enzyme BRCC36-containing isopeptidase complex and plays important roles in cellular responses to stress by interacting with its binding partners, such as ubiquitin-specific peptidase 7, p53, activating transcription factor 4, THAP-domain containing 5, and serine hydroxymethyltransferase. However, the transcriptional regulation of ABRO1 remains unexplored. In this study, we identified and characterized the core regulatory elements of the human ABRO1 gene and mapped them to the ABRO1 promoter region. Additionally, 5' rapid amplification of cDNA ends revealed that the transcriptional start site (TSS) was located -13 bp upstream from the start codon. Reporter gene, chromatin immunoprecipitation, and electrophoretic mobility shift assays demonstrated that ABRO1 transcription was regulated through cis-acting elements located in the region -89 to -59 bp upstream of the ABRO1 TSS and that these elements were targeted by yin yang 1 transcription factor (YY1). Moreover, YY1 overexpression increased human ABRO1 mRNA and protein expression, and small-interfering RNA-mediated downregulation of YY1 attenuated ABRO1 expression. These results suggested that YY1 positively regulated human ABRO1 expression by binding to cis-acting elements located in the ABRO1 TSS.

NLRC4 Mutation in flagellin-derived peptide CBLB502 ligand-binding domain reduces the inflammatory response but not radioprotective activity.

Bacterial flagellin is a pathogen-associated molecular pattern recognized by surface-localized Toll-like receptor 5 (TLR5) and cytosolic NOD-like receptor protein 4 (NLRC4). CBLB502, derived from Salmonella flagellin, exhibits high radioprotective efficacy in mice and primates by regulating TLR5 and the nuclear factor kappa B (NF-κB) signaling pathway. In this study, we examined the effects of CBLB502 and mutations in its NLRC4- and TLR5-binding domains on radioprotective efficacy and the immune inflammatory response. The results showed that CBLB502 mutation with I213A in the TLR5-binding domain significantly reduced NF-κB activity and radioprotective activity, whereas CBLB502 mutation with L292A in NLRC4-binding domain did not. Additionally, CBLB502 with both mutations greatly reduced NF-κB activity and eliminated radioprotection in mice. In contrast, NLRC4-binding domain mutation reduced the secretion of inflammatory interleukin-1ß and interleukin-18. CBLB502 exerts its radioprotective effects through both the TLR5 and NLRC4 pathways. Additionally, deletion in the NLRC4-binding domain did not reduce radioprotective activity but reduced the inflammatory response.

A new pyridine alkaloid from Zingiberis rhizoma.

A new alkaloid, named 2-methoxy-4-(2-(2-pyridine)-ethyl) phenol (1), together with two known compounds, was isolated from Zingiberis rhizoma. Their structures were elucidated on the basis of 1D and 2D NMR spectra and MS spectra. Compound 1 exhibited substantial bioactivity against Canidia albicans ATCC 10231 with a minimum inhibitory concentration of 1.0 mg/mL.