DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.     

Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.     

食品安全国家标准中维生素的测定方法及进展

人体所必需的营养素除了蛋白质、脂类、糖类等能量物质外,维生素也是不可或缺的营养物质,是评价其营养质量的关键指标。检测食品中的维生素含量,是有效保证其质量与安全的必要条件。因此,对现有国家标准食品中维生素的检测方法进行综述,总结各方法的前处理及检出限等,为增强检测工作效率,以及食品检测方法的研究和发展提供参考。     

In vivo Targeting of DNA Vaccines to Dendritic Cells via the Mannose Receptor Induces Long-Lasting Immunity against Melanoma

Herein, we report effective, C-type lectin mannose receptor (MR)-selective, in vivo dendritic cell (DC)-targeting lipid nanoparticles (LNPs) of a novel lipid-containing mannose-mimicking di-shikimoyl- and guanidine head group and two n-hexadecyl hydrophobic tails (DSG). Subcutaneous administration of LNPs of the DSG/p-CMV-GFP complex showed a significant expression of green fluorescence protein in the CD11c⁺ DCs of the neighboring lymph nodes compared to the control LNPs of the BBG/p-CMV-GFP complex. Mannose receptor-facilitated in vivo DC-targeted vaccination (s.c.) with the electrostatic complex of LNPs of DSG/pCMV-MART1 stimulated long-lasting (270 days post B16F10 tumor challenge) antimelanoma immunity under prophylactic conditions. Remarkably, under therapeutic settings, vaccination (s.c.) with LNPs of the DSG/pCMV-MART1 complex significantly delayed melanoma growth and improved the survival of mice with melanoma. These findings demonstrate that this nonviral delivery system offers a resilient and potential approach to deliver DNA vaccines encoding tumor antigens to DCs in vivo with high efficacy.     

Evaluation of a Novel Plasmid for Simultaneous Gene Electrotransfer-Mediated Silencing of CD105 and CD146 in Combination with Irradiation

Targeting tumor vasculature through specific endothelial cell markers represents a promising approach for cancer treatment. Here our aim was to construct an antibiotic resistance gene-free plasmid encoding shRNAs to simultaneously target two endothelial cell markers, CD105 and CD146, and to test its functionality and therapeutic potential in vitro when delivered by gene electrotransfer (GET) and combined with irradiation (IR). Functionality of the plasmid was evaluated by determining the silencing of the targeted genes using qRT-PCR. Antiproliferative and antiangiogenic effects were determined by the cytotoxicity assay tube formation assay and wound healing assay in murine endothelial cells 2H-11. The functionality of the plasmid construct was also evaluated in malignant melanoma tumor cell line B16F10. Additionally, potential activation of immune response was measured by induction of DNA sensor STING and proinflammatory cytokines by qRT-PCR in endothelial cells 2H-11. We demonstrated that the plasmid construction was successful and can efficiently silence the expression of the two targeted genes. As a consequence of silencing, reduced migration rate and angiogenic potential was confirmed in 2H-11 endothelial cells. Furthermore, induction of DNA sensor STING and proinflammatory cytokines were determined, which could add to the therapeutic effectiveness when used in vivo. To conclude, we successfully constructed a novel plasmid DNA with two shRNAs, which holds a great promise for further in vivo testing.     

Translesion Synthesis or Repair by Specialized DNA Polymerases Limits Excessive Genomic Instability upon Replication Stress

DNA can experience “replication stress”, an important source of genome instability, induced by various external or endogenous impediments that slow down or stall DNA synthesis. While genome instability is largely documented to favor both tumor formation and heterogeneity, as well as drug resistance, conversely, excessive instability appears to suppress tumorigenesis and is associated with improved prognosis. These findings support the view that karyotypic diversity, necessary to adapt to selective pressures, may be limited in tumors so as to reduce the risk of excessive instability. This review aims to highlight the contribution of specialized DNA polymerases in limiting extreme genetic instability by allowing DNA replication to occur even in the presence of DNA damage, to either avoid broken forks or favor their repair after collapse. These mechanisms and their key regulators Rad18 and Polθ not only offer diversity and evolutionary advantage by increasing mutagenic events, but also provide cancer cells with a way to escape anti-cancer therapies that target replication forks.     

稳产国Ⅵ柴油并兼产喷气燃料技术方案的工业应用

介绍了浙江石油化工有限公司新建的3 Mt/a柴油加氢精制装置，其配套使用中国石化石油化工科学研究院有限公司开发的催化剂级配技术，并实施了可根据原料供应及市场产品需求情况灵活调整切换的2种生产技术方案。1 a的安稳生产运行结果表明:该装置以直馏柴油为主原料，通过分馏塔的馏分切割及其侧线抽出，实现了稳产国Ⅵ柴油并兼产喷气燃料技术方案的工业化应用；在实施以兼产喷气燃料为主的生产技术方案时，通过调整常一线柴油的掺炼量，不仅可以生产含硫量小于10.0 μg/g的精制柴油产品，同时兼产所得到的喷气燃料产品含硫量小于0.5 μg/g，赛波特颜色号值大于30；在实施主产精制柴油组分方案时，通过掺炼质量分数为20%~40%的催化柴油，并使所提炼得到的精制柴油组分含硫量小于6.0 μg/g的前提下，这些精制柴油组分产品既可直接作为满足国Ⅵ柴油产品出厂待售，也可作为柴油调和组分储存待用于产品的进一步优化。     

Deterministic and probabilistic ship pitch prediction using a multi-predictor integration model based on hybrid data preprocessing,reinforcement learning and improved QRNN

The deterministic and probabilistic prediction of ship motion is important for safe navigation and stable real-time operational control of ships at sea. However, the volatility and randomness of ship motion, the non-adaptive nature of single predictors and the poor coverage of quantile regression pose serious challenges to uncertainty prediction, making research in this field limited. In this paper, a multi-predictor integration model based on hybrid data preprocessing, reinforcement learning and improved quantile regression neural network (QRNN) is proposed to explore the deterministic and probabilistic prediction of ship pitch motion. To validate the performance of the proposed multi-predictor integrated prediction model, an experimental study is conducted with three sets of actual ship longitudinal motions during sea trials in the South China Sea. The experimental results indicate that the root mean square errors (RMSEs) of the proposed model of deterministic prediction are 0.0254°, 0.0359°, and 0.0188°, respectively. Taking series #2 as an example, the prediction interval coverage probabilities (PICPs) of the proposed model of probability predictions at 90%, 95%, and 99% confidence levels (CLs) are 0.9400, 0.9800, and 1.0000, respectively. This study signifies that the proposed model can provide trusted deterministic predictions and can effectively quantify the uncertainty of ship pitch motion, which has the potential to provide practical support for ship early warning systems.     

基准平面垂直断面法在爆破漏斗试验中的应用

系统阐述了基准平面垂直断面法在爆破漏斗试验中测量爆破漏斗体积的基本原理,并将隧道激光断面仪应用于金厂河矿1 750 m水平15^#采场底部切割巷道爆破漏斗试验爆破漏斗体积测量中。通过与传统体重法等计算法所得漏斗体积分析比较,结果表明基于隧道激光断面仪与3D Mine软件分析的基准平面垂直断面法实用性强、操作方便、结果直观可靠,达到试验预期目的。     

Machine fault diagnosis with small sample based on variational information constrained generative adversarial network

In actual engineering scenarios, limited fault data leads to insufficient model training and over-fitting, which negatively affects the diagnostic performance of intelligent diagnostic models. To solve the problem, this paper proposes a variational information constrained generative adversarial network (VICGAN) for effective machine fault diagnosis. Firstly, by incorporating the encoder into the discriminator to map the deep features, an improved generative adversarial network with stronger data synthesis capability is established. Secondly, to promote the stable training of the model and guarantee better convergence, a variational information constraint technique is utilized, which constrains the input signals and deep features of the discriminator using the information bottleneck method. In addition, a representation matching module is added to impose restrictions on the generator, avoiding the mode collapse problem and boosting the sample diversity. Two rolling bearing datasets are utilized to verify the effectiveness and stability of the presented network, which demonstrates that the presented network has an admirable ability in processing fault diagnosis with few samples, and performs better than state-of-the-art approaches.