Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The role of Mitochondrial Fission Proteins in Mitochondrial Dynamics in Kidney Disease

Mitochondria have many forms and can change their shape through fusion and fission of the outer and inner membranes, called “mitochondrial dynamics”. Mitochondrial outer membrane proteins, such as mitochondrial fission protein 1 (FIS1), mitochondrial fission factor (MFF), mitochondrial 98 dynamics proteins of 49 kDa (MiD49), and mitochondrial dynamics proteins of 51 kDa (MiD51), can aggregate at the outer mitochondrial membrane and thus attract Dynamin-related protein 1 (DRP1) from the cytoplasm to the outer mitochondrial membrane, where DRP1 can perform a scissor-like function to cut a complete mitochondrion into two separate mitochondria. Other organelles can promote mitochondrial fission alongside mitochondria. FIS1 plays an important role in mitochondrial–lysosomal contacts, differentiating itself from other mitochondrial-fission-associated proteins. The contact between the two can also induce asymmetric mitochondrial fission. The kidney is a mitochondria-rich organ, requiring large amounts of mitochondria to produce energy for blood circulation and waste elimination. Pathological increases in mitochondrial fission can lead to kidney damage that can be ameliorated by suppressing their excessive fission. This article reviews the current knowledge on the key role of mitochondrial-fission-associated proteins in the pathogenesis of kidney injury and the role of their various post-translational modifications in activation or degradation of fission-associated proteins and targeted drug therapy

Core competence evaluation standards for emergency nurse specialist: Developing and testing psychometric properties

Introduction: Nurse specialists are being cultivated and trained in China to cope with the international development of nursing discipline. However, an empirical summary and reviews of literature have shown a lack of core competence evaluation standards for emergency nurse specialists (ENSs) in China. ENS training has been conducted in several regions without any effective competence evaluation standards. This paper describes the development and psychometric testing of the Core Competence Evaluation Standards for Emergency Nurse Specialists (CCESENS) in the Chinese context. Methods: Several rigorous research methods were applied. The proposed evaluation process consisted of two phases with seven steps. First, the Core Competence Framework Model for Emergency Nurse Specialist (CCFMENS) was established, and 118 items were generated through a review of literature, theoretical analysis, and expert interviews. Drafts of the dimensions and items were evaluated by two-round Delphi methods. Analysis hierarchy process was used to determine the weight of each dimension. Second, field testing was performed among 138 senior emergency nurses. Internal consistency and correlation analysis were applied to test the reliability and validity of the model. Results: The CCESENS consisted of five first-level dimensions, 16 second-level dimensions, and 55 items. Cronbach's α coefficient of overall standards was 0.972, and each dimension ranged from 0.508 to 0.972. Expert content validity index was 0.818, and the correlation coefficients of the five first-level dimensions with the overall standards CCESENS ranged from 0.701 to 0.886 (P < 0.05). Discussion: The CCESENS demonstrated sound internal consistency reliability, content validity, and construct validity. The proposed standard provides an objective standard and reference for assessing, training, and evaluating core competence of ENS

Multi-ion erosion test and molecular dynamics simulation of carbon nanotube concrete under stray current and salt brine environment

This study considers the superior mechanical properties of carbon nanotube concrete (CNC) and conducts corrosion tests over varying durations to investigate key aspects such as corrosion depth, strength loss, ion migration patterns, and microscopic morphological changes in CNC under the influence of stray current in a salt brine environment. Through compressive strength test, chloride ion color test, ion content titration test, microscopic detection test and molecular dynamics simulation, the results show that in an environment where multiple erosive ions coexist, sulfate ions are the most erosive ions to CNC, and are easily combined with calcium ions. The electric field speeds up the transmission of ions, especially chloride ions. Carbon nanotube has a certain adsorption effect on sulfate ions. The main corrosion products are ettringite, gypsum and magnesium hydroxide. Among them, ettringite and gypsum mainly cause expansion and corrosion

lncRNA OTUD6B-AS1 Exacerbates As2O3-Induced Oxidative Damage in Bladder Cancer via miR-6734-5p-Mediated Functional Inhibition of IDH2

Arsenic trioxide (As2O3) is a promising effective chemotherapeutic agent for cancer treatment; however, how and through what molecular mechanisms the oxidative damage of As2O3 is controlled remains poorly understood. Recently, the involvement of dysregulated long noncoding RNA ovarian tumor domain containing 6B antisense RNA1 (lncRNA OTUD6B-AS1) in tumorigenesis is established. Here, for the first time, we characterize the regulation of As2O3 in the oxidative damage against bladder cancer via lncRNA OTUD6B-AS1. As2O3 could activate lncRNA OTUD6B-AS1 transcription in bladder cancer cells, and these findings were validated in a xenograft tumor model. Functional assays showed that lncRNA OTUD6B-AS1 dramatically exacerbated As2O3-mediated oxidative damage by inducing oxidative stress. Mechanistically, As2O3 increased levels of metal-regulatory transcription factor 1 (MTF1), which regulates lncRNA OTUD6B-AS1, in response to oxidative stress. Further, lncRNA OTUD6B-AS1 inhibited mitochondrial NADP+-dependent isocitrate dehydrogenase 2 (IDH2) expression by stabilizing miR-6734-5p, which contributed to cytotoxicity by enhancing oxidative stress. Together, our findings offer new insights into the mechanism of As2O3-induced oxidative damage and identify important factors in the pathway, As2O3/lncRNA OTUD6B-AS1/miR-6734-5p/IDH2, expanding the knowledge of activity of As2O3 as cancer treatment

Maize Purple Plant Pigment Protects Against Fluoride-Induced Oxidative Damage of Liver and Kidney in Rats

Anthocyanins are polyphenols and well known for their biological antioxidative benefits. Maize purple plant pigment (MPPP) extracted and separated from maize purple plant is rich in anthocyanins. In the present study, MPPP was used to alleviate the adverse effects generated by fluoride on liver and kidney in rats. The results showed that the ultrastructure of the liver and kidney in fluoride treated rats displayed shrinkage of nuclear and cell volume, swollen mitochondria and endoplasmic reticulum and vacuols formation in the liver and kidney cells. MPPP significantly attenuated these fluoride-induced pathological changes. The MDA levels in serum and liver tissue of fluoride alone treated group were significantly higher than those of the control group (p &lt; 0.05). The presence of 5 g/kg MPPP in the diet reduced the elevation of MDA levels in blood and liver, and increased the SOD and GSH-Px activities in kidney and GSH level in liver and kidney compared with the fluoride alone treated group (p &lt; 0.05). In addition, MPPP alleviated the decrease of Bcl-2 protein expression and the increase of Bax protein expression induced by fluoride. This study demonstrated the protective role of MPPP against fluoride-induced oxidative stress in liver and kidney of rats