Revolutionary multi-omics analysis revealing prognostic signature of thyroid cancer and subsequent in vitro validation of SNAI1 in mediating thyroid cancer progression through EMT.

Thyroid carcinoma (TC), the most commonly diagnosed malignancy of the endocrine system, has witnessed a significant rise in incidence over the past few decades. The integration of scRNA-seq with other sequencing approaches offers researchers a distinct perspective to explore mechanisms underlying TC progression. Therefore, it is crucial to develop a prognostic model for TC patients by utilizing a multi-omics approach. We acquired and processed transcriptomic data from the TCGA-THCA dataset, including mRNA expression profiles, lncRNA expression profiles, miRNA expression profiles, methylation chip data, gene mutation data, and clinical data. We constructed a tumor-related risk model using machine learning methods and developed a consensus machine learning-driven signature (CMLS) for accurate and stable prediction of TC patient outcomes. 2 strains of undifferentiated TC cell lines and 1 strain of PTC cell line were utilized for in vitro validation. mRNA, protein levels of hub genes, epithelial-mesenchymal transition (EMT)-associated phenotypes were detected by a series of in vitro experiments. We identified 3 molecular subtypes of TC based on integrated multi-omics clustering algorithms, which were associated with overall survival and displayed distinct molecular features. We developed a CMLS based on 28 hub genes to predict patient outcomes, and demonstrated that CMLS outperformed other prognostic models. TC patients of relatively lower CMLS score had significantly higher levels of T cells, B cells, and macrophages, indicating an immune-activated state. Fibroblasts were predominantly enriched in the high CMLS group, along with markers associated with immune suppression and evasion. We identified several drugs that could be suitable for patients with high CMLS, including Staurosporine_1034, Rapamycin_1084, gemcitabine, and topotecan. SNAI1 was elevated in both undifferentiated TC cell lines, comparing to PTC cells. Knockdown of SNAI1 reduced the cell proliferation and EMT phenotypes of undifferentiated TC cells. Our findings highlight the importance of multi-omics analysis in understanding the molecular subtypes and immune characteristics of TC, and provide a novel prognostic model and potential therapeutic targets for this disease. Moreover, we identified SNAI1 in mediating TC progression through EMT in vitro.

Strain Regulation of Mixed-Halide Perovskites Enables High-Performance Wide-Bandgap Photovoltaics.

Wide-bandgap mixed-halogen perovskite materials are widely used as top cells in tandem solar cells. However, serious open-circuit voltage (Voc) loss restricts the power conversion efficiency (PCE) of wide-bandgap perovskite solar cells (PSCs). Herein, it is shown that the resulting methylammonium vacancies induce lattice distortion in methylammonium chloride-assisted perovskite film, resulting in an inhomogeneous halogen distribution and low Voc. Thus, a lattice strain regulation strategy is reported to fabricate high-performance wide-bandgap PSCs. Rubidium (Rb) cations are introduced to fill the A-site vacancy caused by the methylammonium volatilization, which alleviates shrinkage strain of the perovskite crystal. The reduced lattice distortion and increased halide ion migration barrier result in a homogeneous mixed-halide perovskite film. Due to improved carrier transport and suppressed nonradiative recombination, the Rb-treated wide-bandgap PSC (1.68 eV) achieves an excellent PCE of 21.72%, accompanied by a high Voc of 1.22 V. The resulting device maintains more than 90% of its initial PCE after 1500 h under 1-sun illumination conditions.

Midbrain FA initiates neuroinflammation and depression onset in both acute and chronic LPS-induced depressive model mice.

Both exogenous gaseous and liquid forms of formaldehyde (FA) can induce depressive-like behaviors in both animals and humans. Stress and neuronal excitation can elicit brain FA generation. However, whether endogenous FA participates in depression occurrence remains largely unknown. In this study, we report that midbrain FA derived from lipopolysaccharide (LPS) is a direct trigger of depression. Using an acute depressive model in mice, we found that one-week intraperitoneal injection (i.p.) of LPS activated semicarbazide-sensitive amine oxidase (SSAO) leading to FA production from the midbrain vascular endothelium. In both in vitro and in vivo experiments, FA stimulated the production of cytokines such as IL-1ß, IL-6, and TNF-α. Strikingly, one-week microinfusion of FA as well as LPS into the midbrain dorsal raphe nucleus (DRN, a 5-HT-nergic nucleus) induced depressive-like behaviors and concurrent neuroinflammation. Conversely, NaHSO3 (a FA scavenger), improved depressive symptoms associated with a reduction in the levels of midbrain FA and cytokines. Moreover, the chronic depressive model of mice injected with four-week i.p. LPS exhibited a marked elevation in the levels of midbrain LPS accompanied by a substantial increase in the levels of FA and cytokines. Notably, four-week i.p. injection of FA as well as LPS elicited cytokine storm in the midbrain and disrupted the blood-brain barrier (BBB) by activating microglia and reducing the expression of claudin 5 (CLDN5, a protein with tight junctions in the BBB). However, the administration of 30 nm nano-packed coenzyme-Q10 (Q10, an endogenous FA scavenger), phototherapy (PT) utilizing 630-nm red light to degrade FA, and the combination of PT and Q10, reduced FA accumulation and neuroinflammation in the midbrain. Moreover, the combined therapy exhibited superior therapeutic efficacy in attenuating depressive symptoms compared to individual treatments. Thus, LPS-derived FA directly initiates depression onset, thereby suggesting that scavenging FA represents a promising strategy for depression treatment.

Lattice Strain Regulation Enables High-Performance Formamidinium Perovskite Photovoltaics.

Formamidinium lead iodide (FAPbI3 ) perovskite possesses an ideal optical bandgap and is a potential material for fabricating the most efficient single-junction perovskite solar cells (PSCs). Nevertheless, large formamidinium (FA) cations result in residual lattice strain, which reduces the power conversion efficiency (PCE) and operational stability of PSCs. Herein, the modulation of lattice strain in FAPbI3 crystals via a π-conjugated organic amine, i.e., 4-pyrene oxy butylamine (PYBA), is proposed. PYBA pairs at the grain boundary serve as a template for the crystallization of FAPbI3 perovskite, thereby inducing a highly oriented crystal and a pure α-phase film. The PYBA pairs with strong π-π interactions provide a solid fulcrum for external compression strain, thus compensating for the inherent tension strain of FAPbI3 crystals. The strain release elevates the valence band of the perovskite crystals, thereby decreasing the bandgap and trap density. Consequently, the PYBA-regulated FAPbI3 PSC achieves an excellent PCE of 24.76%. Moreover, the resulting device exhibits improves operational stability and maintains over 80% of its initial PCE after 1500 h under maximum power point tracking conditions.

Genome-wide characterization of the PLATZ gene family in watermelon (Citrullus lanatus L.) with putative functions in biotic and abiotic stress response.

Plant AT-rich sequence and zinc-binding (PLATZ) proteins are plant-specific transcription factors involved in growth, development, and stress responses. Here, we conducted a genome-wide characterization of the watermelon ClPLATZ family and examined its expression responsiveness to defense hormones and pathogen infection along with putative functions in biotic and abiotic stress responses. The watermelon genome contains 12 putative ClPLATZ genes, encoding proteins with a characteristic PLATZ domain, and their promoters contain various cis-elements related to plant growth, development, phytohormones and stress response. The ClPLATZ genes, except ClPLATZ6, are differentially expressed in response to defense hormones (e.g., salicylic acid and methyl jasmonate) and fungal infections caused by Fusarium oxysporum f. sp. niveum and Stagonosporopsis cucurbitacearum. Most ClPLATZ proteins interact with other proteins (viz., ClDP, ClRPT2a, and ClRPC53). Among ClPLATZ proteins, ClPLATZ8, 9, 10, and 11 are predominately localized in the nucleus. ClPLATZ3 and 8 positively, but ClPLATZ11 negatively regulate resistance against Pseudomonas syringe pv. tomato DC3000 in transgenic Arabidopsis lines. ClPLATZ8 and 11 positively regulate stress tolerance to NaCl and mannitol during seed germination in transgenic Arabidopsis. In conclusion, the characterization of the ClPLATZ family provides insights into the biological functions of ClPLATZ genes in growth, development, and stress response in watermelon. Further, the involvement of certain ClPLATZ genes in biotic and abiotic stress response in transgenic Arabidopsis suggests their potential application in engineering stress-tolerant crops.

Associations of MTHFR Polymorphisms and Cytosine Modifications with Early-Gestational Diabetes Mellitus in Chinese Pregnant Women.

Early-Gestational Diabetes Mellitus (Early-GDM) is a complex condition that may cause complications in infants of affected mothers. The aim of this case-control study was to analyze the effects of genetic-epigenetic interaction on Early-GDM and fetal development with respect to cytosine modifications (i.e., 5mC, 5-methylcytosines; and 5hmC, 5-hydroxymethylcytosines) and single nucleotide polymorphisms (SNPs) of MTHFR, a key gene involving cytosine modifications. Peripheral blood samples were collected from 92 women in their first or second trimester of pregnancy (Early-GDM, n = 14; Controls, n = 78). Global DNA 5mC and 5hmC were quantified by HPLC-MS/MS, and MTHFR SNPs (rs1801133 C > T and rs1801131 A > C) were determined by TaqMan-qPCR. Association analysis suggested that MTHFR rs1801133 TT genotype was a risk factor of Early-GDM (OR [odds ratio] = 4.00; 95% CI [confidence interval]: 1.24, 12.86; p = 0.02). The C allele of rs1801131 appeared to be a protective factor for the 2-h OGTT (oral glucose tolerance test) (OR = -0.79; 95% CI: -1.48, -0.10; p = 0.03). Patients with Early-GDM had higher global 5mC and lower global 5hmC. The reduction of global 5hmC and the TT genotype of rs1801133 were associated with higher level of the 1st-FBG (fasting blood glucose in the first trimester) (p < 0.05). Additionally, global 5mC showed a positive correlation with birth weight, body length and head circumference of newborns, while global 5hmC showed a negative correlation with birth weight. The current study implicated MTHFR SNPs and cytosine modifications in the development of Early-GDM and potential complications in their newborns.

Correlation analysis between extrusion process variables and quality of purslane leaf powder rice extrudates.

Extrusion has become one of the most popular techniques in food processing, and the process parameters are closely related to product quality. Purslane (Portulaca oleracea L.) can be used in medical and food products as a vegetable and herb. It has limited application in extrusion. The effects of extrusion process variables (screw speed, barrel temperature, and feed moisture) on system variables (specific mechanical energy [SME], die head pressure, and torque) and target variables (water absorption index, water solubility index, iodine blue value, color, pasting properties, and textural properties) of purslane powder compound rice were studied. The results showed that SME was moderately positively correlated with screw speed (r = 0.608, p < 0.05). However, torque was moderately negatively correlated with feed moisture (r = -0.574, p < 0.05), and die head pressure was moderately negatively correlated with barrel temperature (r = -0.635, p < 0.01). The target variables of extrudates were also correlated with the system parameters to varying degrees. These results are helpful to control and predict the texture, pasting properties, and other quality characteristics of extruded products containing purslane powder. PRACTICAL APPLICATION: The results showed that torque and die head pressure were moderately negatively related to barrel temperature, specific mechanical energy was moderately positively related to screw speed, peak viscosity and breakdown viscosity were moderately negatively related to specific mechanical energy, and water absorption index was moderately negatively related to torque and die head pressure. It provides a reference for the research of influencing system parameters and changing product quality by controlling extrusion process parameters. In this study, some possibilities for the application of broken rice and purslane in extrusion processing were proposed.

A holistic framework of water quality evaluation using water quality index (WQI) in the Yihe River (China).

The Yihe River is an important river in Shandong Province, China. It is a catchment river for the South-to-North Water Diversion Project (SNWDP-ER), providing a variety of benefits and ecosystem services, such as flood and drought regulation, fishery and aquaculture, drinking water sources, and biodiversity conservation. In order to objectively reflect the status and changing trend of water environmental quality of the Yihe River, reduce the cost of detection, and improve the efficiency of water quality evaluation, samples were collected at 8 sampling sites in the 220 km main stream of the Yihe River from 2009 to 2019. The spatiotemporal variations of 10 water quality indicators were analyzed, including pH, water temperature (WT), dissolved oxygen (DO), 5-day biochemical oxygen demand (BOD5), chemical oxygen demand (COD), total phosphorus (TP), ammonia nitrogen (NH3-N), nitrate (NO3-N), fluoride (F-), and sulphate (SO42-). The water quality index (WQI) was used to evaluate the spatiotemporal water quality changes, and the minimum WQI (WQImin) model consisting of five key indicators, i.e., NH3-N, BOD5, DO, SO42-, and WT, was built by using stepwise multiple linear regression analysis. The results indicated that the water quality indicators in the Yihe River showed significant spatiotemporal variations. With the exception of the COD and TP, the other water quality indicators conformed to the Class I or II standards of China, indicating that the water quality of the Yihe River was better than most natural water bodies. Seasonally, the WQI was better in the autumn and higher in the upstream area compared to the downstream. The water quality remained at the "good" level. The weighted WQImin model performed well in evaluating water quality, with coefficient of determination (R2), mean square error (MSE), and percentage error (PE) values of 0.903, 3.05, and 1.70%, respectively.

Microstructure and load bearing capacity of TiN/NbN superlattice coatings deposited on medical grade CoCrMo alloy by HIPIMS.

In recent years significant progress has been made in the application of various ceramic, namely Metal nitride (MeN) functional coatings to engineer the surfaces of medical implants utilising metal-on-metal (MoM) articulation. This article reports on the load bearing capacity and structural response of TiN/NbN superlattice coatings deposited on medical grade CoCrMo alloy substrate under the application of localised load and the subsequent crack formation mechanism. The coatings have been deposited by mixed High Power Impulse Magnetron Sputtering-Unbalanced Magnetron Sputtering (HIPIMS-UBM) process. In the case of TiN/NbN coating deposited on CoCrMo substrate where Ecoating/Esubstrate is as high as 1.81 indicating that the substrate does not provide the necessary load bearing support for the brittle thin film, the utilisation of the Berkovich indentation technique proved to be a potent approach to study coating material as well as structural response to applied concentrated load. FIB/SEM analyses of the indented coatings revealed that in the hard-on-soft material systems cracks will initiate due to sub-coating substrate deformation and then propagate towards the coating surface. The FIB/SEM and low magnification XTEM analysis showed that an exceptionally strong TiN/NbN coating substrate adhesion bonding was achieved due to the utilisation of the HIPIMS pre-treatment. High resolution XTEM analyses revealed, for the first time, that during the indentation a collective rotation and alignment of the individual layers of the superlattice stack takes place without compromising coatings integrity which is clear evidence for the exeptionally high coating fracture toughness. The high toughness of the superlattice structured TiN/NbN coatings combined with their exceptionally high adhesion on madical grade CoCrMo ranks them as a strong candidate for medical implant applications.

Genome Sequence Resource for Stagonosporopsis cucurbitacearum, a Cause of Gummy Stem Blight Disease of Watermelon.

Gummy stem blight (GSB), which is caused by three related species of Stagonosporopsis, is a worldwide devastating disease of cucurbit crops including watermelon. Previously S. cucurbitacearum was reported to be the major fungal cause of watermelon GSB in Southern China, where it causes a significant decrease in watermelon yield. Here, we present the draft whole genome sequence, gene prediction and annotation of S. cucurbitacearum strain DBTL4, isolated from diseased watermelon plants. To our knowledge, this is the first publicly available genome sequence of this species, and knowledge of this genome sequence will help further understand the pathogenic mechanism of S. cucurbitacearum to cucurbit plants.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Simulation and Experiment on Droplet Formation and Separation for Needle-Type Micro-Liquid Jetting Dispenser.

The needle-type droplet jetting dispenser has wide applications in the field of microelectronic packaging, and for which the good quality of droplet formation and separation is the key to successful dispensing. This paper simulates the droplet jetting process which has been divided into 5 stages named backflow, growth, droplet extension, breakage, and separation, and analyses the combined effects of system parameters, such as pressure, viscosity, needle stroke, and nozzle diameter, on the changes of morphologies of ejected droplets, which is verified by experiments. The simulation and experiment results show that a higher driving pressure is quite suitable for the high-viscosity liquid to form normal droplets by avoiding adhesion. When increasing the needle stroke, the pressure should also be lowered properly to prevent the flow-stream. Besides, the nozzle with a large diameter is much more likely to cause sputtering or satellite-droplet problems. The results have a great significance for guiding the parameter settings of the needle-type dispensing approach.

Understanding surface structure and chemistry of single crystal lanthanum aluminate.

The surface crystallography and chemistry of a LaAlO3 single crystal, a material mainly used as a substrate to deposit technologically important thin films (e.g. for superconducting and magnetic devices), was analysed using surface X-ray diffraction and low energy ion scattering spectroscopy. The surface was determined to be terminated by Al-O species, and was significantly different from the idealised bulk structure. Termination reversal was not observed at higher temperature (600 °C) and chamber pressure of 10-10 Torr, but rather an increased Al-O occupancy occurred, which was accompanied by a larger outwards relaxation of Al from the bulk positions. Changing the oxygen pressure to 10-6 Torr enriched the Al site occupancy fraction at the outermost surface from 0.245(10) to 0.325(9). In contrast the LaO, which is located at the next sub-surface atomic layer, showed no chemical enrichment and the structural relaxation was lower than for the top AlO2 layer. Knowledge of the surface structure will aid the understanding of how and which type of interface will be formed when LaAlO3 is used as a substrate as a function of temperature and pressure, and so lead to improved design of device structures.

HMGB1-RAGE signaling pathway in severe preeclampsia.

INTRODUCTION: Placental dysfunction and increased inflammation are believed to underlie the pathogenesis of severe preeclampsia (PE). High-mobility group box 1 (HMGB1), a recently identified inflammatory cytokine, has been known to contribute to the development of inflammatory responses in PE. This study intends to elucidate the mechanisms of HMGB1-RAGE signaling pathway in the pathogenesis of PE. METHODS: The mRNA levels of relative gene of HMGB1 pathway, HMGB1, RAGE and NF-κB p65, were analyzed by real-time PCR in placentas collected from 61 normotensive pregnant women and 64 women with severe PE. Additionally, levels of HMGB1 and RAGE protein were detected in frozen placental specimens by western blot, and the locations of them were evaluated in the well-characterized tissue microarray by immunohistochemistry. ELISA was further used to detect HMGB1 level in maternal serum. RESULTS: Compared with matched control placentas, the mRNA levels of HMGB1, RAGE and NF-κB p65 were increased in severe preeclamptic placentas. In severe preeclamptic placentas, HMGB1 and RAGE immunoreactivity were increased in the cytoplasm of trophoblast cells. Western blot was employed to further confirm that RAGE protein level was elevated significantly in severe PE group. In addition, there was an increased level of HMGB1 in the maternal serum of severe PE group. DISCUSSION: HMGB1 nuclear-cytoplasmic translocation may induce the binding of HMGB1 to its receptors, consequently, intrigue NF-κB activity in severe PE. HMGB1-RAGE signaling pathway may be involved in the pathogenesis of PE.

High-resolution melting analysis reveals genetic polymorphisms in microRNAs confer hepatocellular carcinoma risk in Chinese patients.

BACKGROUND: Although several single-nucleotide polymorphisms in microRNA (miRNA) genes have been associated with primary hepatocellular carcinoma, published findings regarding this relationship are inconsistent and inconclusive. METHODS: The high-resolution melting (HRM) analysis was used to determine whether the occurrence of the SNPs of miR-146a C > G (rs2910164), miR-196a2 C > T (rs11614913), miR-301b A > G (rs384262), and miR-499 C > T (rs3746444) differs in frequency-matched 314 HCC patients and 407 controls by age and sex. RESULTS: The groups' genotype distributions of miR-196a2 C > T and miR-499 C > T differed significantly (P < 0.01), both of them increased the risk of HCC in different dominant genetic models (P < 0.01); compared with individuals carrying one or neither of the unfavorable genotypes, individuals carrying both unfavorable genotypes (CT + CC) had a 3.11-fold higher HCC risk (95% confidence interval (CI), 1.89-5.09; P = 7.18 × 10-6). Moreover, the allele frequency of miR-499 C > T was significantly different between the two groups, and the HCC risk of carriers of the C allele was higher than that of carriers of the T allele (odds ratio, 1.53; 95% CI, 1.15-2.03; P = 0.003). Further, we found that the activated partial thromboplastin time (APTT) in HCC patients with miR-196a2 CC genotype was longer than patients with TT genotypes (P < 0.05), and HCC patients with miR-499 C allele had higher serum levels of direct bilirubin, globulin, γ-glutamyltranspeptidase, alkaline phosphatase, and lower serum cholinesterase (P < 0.05). CONCLUSIONS: Our findings suggest that the SNPs in miR-196a2 C > T and miR-499 C > T confer HCC risk and that affect the clinical laboratory characteristics of HCC patients.

Tuning calcite morphology and growth acceleration by a rational design of highly stable protein-mimetics.

In nature, proteins play a significant role in biomineral formation. One of the ultimate goals of bioinspired materials science is to develop highly stable synthetic molecules that mimic the function of these natural proteins by controlling crystal formation. Here, we demonstrate that both the morphology and the degree of acceleration or inhibition observed during growth of calcite in the presence of peptoids can be rationally tuned by balancing the electrostatic and hydrophobic interactions, with hydrophobic interactions playing the dominant role. While either strong electrostatic or hydrophobic interactions inhibit growth and reduces expression of the {104} faces, correlations between peptoid-crystal binding energies and observed changes in calcite growth indicate moderate electrostatic interactions allow peptoids to weakly adsorb while moderate hydrophobic interactions cause disruption of surface-adsorbed water layers, leading to growth acceleration with retained expression of the {104} faces. This study provides fundamental principles for designing peptoids as crystallization promoters, and offers a straightforward screening method based on macroscopic crystal morphology. Because peptoids are sequence-specific, highly stable, and easily synthesized, peptoid-enhanced crystallization offers a broad range of potential applications.

Contribution of energetically reactive surface features to the dissolution of CeO2 and ThO2 analogues for spent nuclear fuel microstructures.

In the safety case for the geological disposal of nuclear waste, the release of radioactivity from the repository is controlled by the dissolution of the spent fuel in groundwater. There remain several uncertainties associated with understanding spent fuel dissolution, including the contribution of energetically reactive surface sites to the dissolution rate. In this study, we investigate how surface features influence the dissolution rate of synthetic CeO2 and ThO2, spent nuclear fuel analogues that approximate as closely as possible the microstructure characteristics of fuel-grade UO2 but are not sensitive to changes in oxidation state of the cation. The morphology of grain boundaries (natural features) and surface facets (specimen preparation-induced features) was investigated during dissolution. The effects of surface polishing on dissolution rate were also investigated. We show that preferential dissolution occurs at grain boundaries, resulting in grain boundary decohesion and enhanced dissolution rates. A strong crystallographic control was exerted, with high misorientation angle grain boundaries retreating more rapidly than those with low misorientation angles, which may be due to the accommodation of defects in the grain boundary structure. The data from these simplified analogue systems support the hypothesis that grain boundaries play a role in the so-called "instant release fraction" of spent fuel, and should be carefully considered, in conjunction with other chemical effects, in safety performance assessements for the geological disposal of spent fuel. Surface facets formed during the sample annealing process also exhibited a strong crystallographic control and were found to dissolve rapidly on initial contact with dissolution medium. Defects and strain induced during sample polishing caused an overestimation of the dissolution rate, by up to 3 orders of magnitude.

Association of 5-methylcytosine and 5-hydroxymethylcytosine with mitochondrial DNA content and clinical and biochemical parameters in hepatocellular carcinoma.

Increasing epidemiological evidence has indicated that inherited variations of mitochondrial DNA (mtDNA) copy number affect the genetic susceptibility of many malignancies in a tumour-specific manner and that DNA methylation also plays an important role in controlling gene expression during the differentiation and development of hepatocellular carcinoma (HCC). Our previous study demonstrated that HCC tissues showed a lower 5-hydroxymethylcytosine (5-hmC) content when compared to tumour-adjacent tissues, but the relationship among 5-hmC, 5-methylcytosine (5-mC) and mtDNA content in HCC patients is still unknown. This study aimed to clarify the correlation among mtDNA content, 5-mC and 5-hmC by quantitative real-time PCR and liquid chromatography tandem mass spectrometry analysis. We demonstrated that 5-hmC correlated with tumour size [odds ratio (OR) 0.847, 95% confidence interval (CI) 0.746-0.962, P = 0.011], and HCC patients with a tumour size ≥ 5.0 cm showed a lower 5-hmC content and higher levels of fasting plasma aspartate aminotransferase, the ratio of alanine aminotransferase to aspartate aminotransferase, γ-glutamyltransferase, alpha-fetoprotein than those with a tumour size <5 cm (all P<0.05). We further revealed that the mtDNA content of HCC tumour tissues was 225.97(105.42, 430.54) [median (25th Percentile, 75th Percentile)] and was negatively correlated with 5-mC content (P = 0.035), but not 5-hmC content, in genomic DNA from HCC tumour tissues.

Quantification of 5-methylcytosine and 5-hydroxymethylcytosine in genomic DNA from hepatocellular carcinoma tissues by capillary hydrophilic-interaction liquid chromatography/quadrupole TOF mass spectrometry.

BACKGROUND: 5-Methylcytosine (5-mC) is an important epigenetic modification involved in development and is frequently altered in cancer. 5-mC can be enzymatically converted to 5-hydroxymethylcytosine (5-hmC). 5-hmC modifications are known to be prevalent in DNA of embryonic stem cells and neurons, but the distribution of 5-hmC in human liver tumor and matched control tissues has not been rigorously explored. METHODS: We developed an online trapping/capillary hydrophilic-interaction liquid chromatography (cHILIC)/in-source fragmentation/tandem mass spectrometry system for quantifying 5-mC and 5-hmC in genomic DNA from hepatocellular carcinoma (HCC) tumor tissues and relevant tumor adjacent tissues. A polymer-based hydrophilic monolithic column was prepared and used for the separation of 12 nucleosides by cHILIC coupled with an online trapping system. Limits of detection and quantification, recovery, and imprecision of the method were determined. RESULTS: Limits of detection for 5-mC and 5-hmC were 0.06 and 0.19 fmol, respectively. The imprecision and recovery of the method were determined, with the relative SDs and relative errors being <14.9% and 15.8%, respectively. HCC tumor tissues had a 4- to 5-fold lower 5-hmC content compared to tumor-adjacent tissues. In addition, 5-hmC content highly correlated with tumor stage (tumor-nodes-metastasis, P = 0.0002; Barcelona Clinic liver cancer, P = 0.0003). CONCLUSIONS: The marked depletion of 5-hmC may have profound effects on epigenetic regulation in HCC and could be a potential biomarker for the early detection and prognosis of HCC.

Age-related distributions of nine fasting plasma free fatty acids in a population of Chinese adults.

BACKGROUND: Free fatty acids (FFAs) play important roles in health and disease. We investigated the distributions of nine plasma FFAs in a population of Chinese adults. METHOD: Three hundred and ninety-nine healthy individuals aged 18-104 years were divided into 4 groups: 18-39 years; 40-59 years; 60-79 years; and 80-104 years. Nine plasma FFAs, including C12:0, C14:0, C16:0, C16:1, C18:0, C18:1 C18:2, C20:4 and C20:5 were determined using a validated HPLC method. RESULTS: There were significant differences among the 4 age groups in the plasma total FFA (TFA), saturated fatty acid (SFA), unsaturated fatty acid (UFA), and eight specific FFA concentrations, and the ratios of SFA to UFA, SFA to TFA, and UFA to TFA as well (all P<0.05), except for FFA C16:1. However, no significant difference was found between males and females. The 4 most abundant FFAs, C16:0, C18:0, C18:1 and C18:2 account for >90% of plasma total FFA. Reference intervals for individual FFAs are set at the 10th-90th percentile. CONCLUSIONS: Significant differences in eight specific plasma FFAs among various age groups were found in a population of Chinese adults. C16:0, C18:0, C18:1 and C18:2 are the most abundant FFAs in the fasting plasma. Reference intervals are established for the local Chinese community.

Engineered biomimetic polymers as tunable agents for controlling CaCO3 mineralization.

In nature, living organisms use peptides and proteins to precisely control the nucleation and growth of inorganic minerals and sequester CO(2)via mineralization of CaCO(3). Here we report the exploitation of a novel class of sequence-specific non-natural polymers called peptoids as tunable agents that dramatically control CaCO(3) mineralization. We show that amphiphilic peptoids composed of hydrophobic and anionic monomers exhibit both a high degree of control over calcite growth morphology and an unprecedented 23-fold acceleration of growth at a peptoid concentration of only 50 nM, while acidic peptides of similar molecular weight exhibited enhancement factors of only ∼2 or less. We further show that both the morphology and rate controls depend on peptoid sequence, side-chain chemistry, chain length, and concentration. These findings provide guidelines for developing sequence-specific non-natural polymers that mimic the functions of natural peptides or proteins in their ability to direct mineralization of CaCO(3), with an eye toward their application to sequestration of CO(2) through mineral trapping.