Bovine Omasum-Inspired Interfacial Carbon-Based Nanocomposite for Saliva Metabolic Screening of Gastric Cancer.

Gastric cancer is one of the most common malignant digestive cancers, and its diagnostic has still faced challenges based on metabolic analysis due to complex sample pretreatment and low metabolite abundance. In this study, inspired by the structure of bovine omasum, we in situ synthesized a novel interfacial carbon-based nanocomposite of graphene supported nickel nanoparticles-encapsulated in the nitrogen-doped carbon nanotube (Ni/N-CNT/rGO), which was served as a novel matrix with enhanced ionization efficiency for the matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) saliva metabolic analysis of gastric cancer. Benefiting from its high sp2 graphitic degree, large surface area, strong UV absorption, and rich active sites, Ni/N-CNT/rGO matrix exhibited excellent performances of reproducibility, coverage, salt-tolerance, sensitivity, and adsorption ability in MALDI-TOF MS. The differential scanning calorimetry (DSC) and thermal conversion behaviors explained the highly efficient LDI mechanism. Based on saliva metabolic fingerprints, Ni/N-CNT/rGO assisted LDI MS with cross-validation analysis could successfully distinguish gastric cancer patients from healthy controls through the screening of four potential biomarkers with an accuracy of 92.50%, specificity of 88.03%, and sensitivity of 97.12%. This work provided a fast and sensitive MS sensing platform for the metabolomics characterization of gastric cancer and might have potential value for precision medicine in the future.

Functional Melanin Nanoparticles-Assisted Laser Desorption Ionization Mass Spectrometry for High-Sensitivity Detection of TBBPA and TBBPS Contaminations in Animal-Derived Foodstuffs.

Tetrabromobisphenol A (TBBPA) and tetrabromobisphenol S (TBBPS) have been widely used as additives in various products; however, their residues damage human health mainly via dietary ingestion. The current detection techniques remain challenging in directly and sensitively identifying TBBPA and TBBPS from food samples. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has great potential as an alternative tool for the analysis of low-mass environmental pollution. Herein, we successfully screened and optimized COOH-MNP-COOH as a novel MALDI matrix to enhance deprotonation for the analysis of TBBPA and TBBPS from animal-derived food samples in negative-ion mode. Notably, COOH-MNP-COOH was synthesized by a facile self-assembly strategy and characterized by TEM, FT-IR, UV-vis, and zeta potential analysis. Compared with conventional and control matrices, the COOH-MNP-COOH matrix exhibited excellent performance of TBBPA and TBBPS with high chemical stability, favorable reproducibility, remarkable salt and protein tolerance, and high sensitivity owing to abundant active groups, stronger UV-vis absorption at 355 nm, and better hydrophilicity and biocompatibility. TBBPA and TBBPS were detected with the assistance of an internal standard with limits of detection (LODs) of 300 and 200 pg/mL, respectively. Moreover, this method was applied to directly identify the residues of TBBPA and TBBPS in milk products, followed by basa catfish and meat. This research may provide a promising approach for the analysis of environmental pollutants in foodstuffs.

Yolk-shell Ni/NiO anchored on N-doped graphene synthesized as dual-ion MALDI matrix for detecting and imaging bioactive small molecules.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an attractive tool to analyze the bioactive small molecules but remains a great challenge owing to the serious background interference from conventional matrix with m/z < 1000. Herein, we reported a dual-ion MALDI matrix of yolk-shell Ni/NiO nanoparticles anchored on nitrogen-doped graphene (Ni/NiO/N-Gr) to enhance MALDI performance. The Ni/NiO/N-Gr was synthesized via the pyrolysis and controllable oxidation strategy based on the nanoscale regulation of Kirkendall effect. The novel matrix showed the superior behavior for the analysis of various small molecular metabolites (amino acids, saccharides, spermidine, creatinine, hippuric acid, dopamine, and ascorbic acid) with high sensitivity, excellent salt tolerance, and favorable reproducibility in dual-ion modes compared to the traditional α-cyano-4-hydroxycinnamic acid (CHCA) and control substances (Ni/N-Gr and NiO/N-Gr). Meanwhile, we have realized accurate quantitation of blood glucose in mice with a linearity concentration range of 0.2-7.5 mM and qualitative detection of various endogenous small molecular metabolites in mice serum and urine samples. Especially, the Ni/NiO/N-Gr assisted LDI MS imaging (MSI) has exhibited the excellent spatial distribution of lipids in hippocampus region of mice brain. These results may provide an approach to explore the MALDI MS and MSI applications in clinical diagnosis.

The local electric field effect of onion-like carbon nanoparticles for improved laser desorption/ionization efficiency of saccharides.

It is still a challenge to improve ionization efficiency of saccharides in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Herein, the highly curved onion-like carbon nanoparticles (OCS) were synthesized from the low-price candle raw via a facile strategy. The unique nanostructure of OCS showed large surface area with plentiful mesoporous architecture, highly curved sp2 carbon with regulating electronic effect, and good hydrophilicity, which could be beneficial to facilitate the desorption and ionization efficiency in MS process. The prepared OCS material as MALDI matrix exhibited the superior performance for the detection of xylose, glucose, maltose monohydrate, and raffinose pentahydrate in positive-ion mode with low background noise, enhanced ion intensities, uniform distribution, excellent reproducibility, good salt-tolerance, and high sensitivity compared to control candle soot (CS) and traditional α-cyano-4-hydroxycinnamic acid (CHCA) matrices. This highly effective LDI of OCS matrix was attributed to its enhancing local electric field effect, strong UV absorption ability, and high photo-thermal conversion performance. Furthermore, the OCS-assisted LDI MS approach was employed to quantitatively detect glucose in rat serum. This LDI MS platform may have valuable for the analysis of metabolites in clinical research.

Effects of dezocine, morphine and nalbuphine on electropain threshold, temperature pain threshold and cardiac function in rats with myocardial ischemia.

BACKGROUND: Myocardial ischemia (MI) could cause many complications, such as arrhythmia, ischemic cardiomyopathy, which could lead to angina and myocardial infarction. The clinical efficacy of dezocine, morphine and nalbuphine are becoming dominated in China market. This aim of this study was to investigate the effects of dezocine, morphine and nalbuphine on electrical pain threshold, temperature pain threshold and cardiac function in rats with MI. METHODS: A rat model of MI was established by ligating the coronary artery. Rats in the model group were injected with dezocine, morphine, nalbuphine and 0.9% normal saline. The effects of the three analgesics on MI rats were evaluated by comparing the electrical pain threshold, temperature pain threshold, and cardiac function index. RESULTS: The electrocardiogram revealed that the model of MI was successful. The results of the electrical pain threshold and temperature pain threshold tests revealed that nalbuphine was the most sensitive after medication, followed by dezocine, and the sensitivity of morphine was the lowest. These three drugs reached its peak at two hours after administration. The analgesic effect of dezocine on electrical stimulation was the best, while nalbuphine had the best effect on temperature. The efficacy of dezocine decreased with time, while morphine basically failed at four hours after administration. The peak time of these three kinds of analgesics was selected to detect the cardiac function index in each group. Morphine had the least influence on the cardiac function index of rats, followed by nalbuphine and dezocine. CONCLUSIONS: These results show that the analgesic effect of nalbuphine had the earliest and best effect with the longest duration on temperature, and had less influence and higher safety in the cardiac function test of MI rats. Hence, nalbuphine is a relatively good analgesic for MI patients. The present study provides a database for the selection of analgesics in patients with MI.

The nucleoskeleton protein IFFO1 immobilizes broken DNA and suppresses chromosome translocation during tumorigenesis.

Chromosome translocation is a major cause of the onset and progression of diverse types of cancers. However, the mechanisms underlying this process remain poorly understood. Here, we identified a non-homologous end-joining protein, IFFO1, which structurally forms a heterotetramer with XRCC4. IFFO1 is recruited to the sites of DNA damage by XRCC4 and promotes the repair of DNA double-strand breaks in a parallel pathway with XLF. Interestingly, IFFO1 interacts with lamin A/C, forming an interior nucleoskeleton. Inactivating IFFO1 or its interaction with XRCC4 or lamin A/C leads to increases in both the mobility of broken ends and the frequency of chromosome translocation. Importantly, the destruction of this nucleoskeleton accounts for the elevated frequency of chromosome translocation in many types of cancer cells. Our results reveal that the lamin A/C-IFFO1-constituted nucleoskeleton prevents chromosome translocation by immobilizing broken DNA ends during tumorigenesis.

Environmental Stress Responses of DnaJA1, DnaJB12 and DnaJC8 in Apis cerana cerana.

DnaJ, also known as Hsp40, plays important roles in maintaining the normal physiological state of an organism under stress conditions by mediating essential processes, such as protein synthesis, degradation, folding and metabolism. However, the exact functions of most DnaJ members are not fully understood in insects. Here, we identified three genes, AccDnaJA1, AccDnaJB12, and AccDnaJC8, in Apis cerana cerana and explored their connection with the environmental stress response. Quantitative real-time PCR results showed that the mRNA levels of AccDnaJA1, AccDnaJB12, and AccDnaJC8 were all induced under cold, UV, H2O2 and different pesticides treatment. The expression patterns of AccDnaJB12 and AccDnaJC8 were upregulated by CdCl2 and HgCl2 stress, while the transcriptional levels of AccDnaJA1 were downregulated by CdCl2 and HgCl2 stress. Western blot findings further indicated that AccDnaJB12 protein levels were increased by some stress conditions. Knockdown of each of these three genes downregulated the transcriptional patterns of several stress response-related genes at different levels. Functional analysis further demonstrated that the resistance of A. cerana cerana to lambda-cyhalothrin stress was reduced with knockdown of AccDnaJA1, AccDnaJB12, or AccDnaJC8, indicating that these three genes may be involved in the tolerance to this pesticide. Taken together, these findings indicate that AccDnaJA1, AccDnaJB12, and AccDnaJC8 may play pivotal roles in the stress response by facilitating honeybee survival under some adverse circumstances. To our knowledge, this is the first report that reveals the roles of DnaJ family proteins under different adverse circumstances in A. cerana cerana.

An OB-fold complex controls the repair pathways for DNA double-strand breaks.

53BP1 with its downstream proteins, RIF1, PTIP and REV7, antagonizes BRCA1-dependent homologous recombination (HR) and promotes non-homologous end joining (NHEJ) in an unclear manner. Here we show that REV7 forms a complex with two proteins, FAM35A and C20ORF196. We demonstrate that FAM35A preferentially binds single-strand DNA (ssDNA) in vitro, and is recruited to DSBs as a complex with C20ORF196 and REV7 downstream of RIF1 in vivo. Epistasis analysis shows that both proteins act in the same pathway as RIF1 in NHEJ. The defects in HR pathway to repair DSBs and the reduction in resection of broken DNA ends in BRCA1-mutant cells can be largely suppressed by inactivating FAM35A or C20ORF196, indicating that FAM35A and C20ORF196 prevent end resection in these cells. Together, our data identified a REV7-FAM35A-C20ORF196 complex that binds and protects broken DNA ends to promote the NHEJ pathway for DSB repair.