pH-mediated upregulation of AQP1 gene expression through the Spi-B transcription factor

Background: Bicarbonate-based peritoneal dialysis (PD) fluids enhance the migratory capacity and damage-repair ability of human peritoneal mesothelial cells by upregulating AQP1. However, little is known about the underlying molecular mechanisms. Results: Here we used HEK-293T cells to investigate the effect of pH on AQP1 gene transcription levels. We found that AQP1 mRNA levels increases with pH. Transfection of HEK-293T cells with luciferase reporter vectors containing different regions of the AQP1 promoter identified an upstream region in the AQP1 gene between − 2200 and – 2300 bp as an enhancer required for pH-mediated regulation of AQP1 expression. Site-directed mutagenesis of this specific promoter region revealed a critical region between − 2257 and − 2251 bp, and gene knock-down experiments and ChIP assays suggested that the Spi-B transcription factor SPIB is involved in pH-mediated regulation of AQP1 expression. Conclusions: We identified an upstream region in the AQP1 gene and the transcription factor SPIB that are critically involved in pH-mediated regulation of AQP1 expression. These findings provide the basis for further studies on the pH- and buffer-dependent effects of PD fluids on peritoneal membrane integrity and function

Bis(η3-2-tert-butyl-1-trimethyl­silyl-3-phenyl-1-aza­all­yl)nickel(II)

The title compound, [Ni(C15H24NSi)2], is a homoleptic metal–η3-aza­allyl centrosymmetric complex containing two aza­allyl ligands bound in an η3-manner to an NiII atom located on a center of symmetry. The overall coordination about the NiII atom is square-planar. The C and N atoms of the aza­allyl group are sp 2-hybridized. The uneven Ni—C and Ni—N distances [2.045 (5)/2.060 (6) and 1.916 (5) Å] are influenced by a steric hindering effect from the nearby benzene ring

Existence of positive solutions for singular p-Laplacian Hadamard fractional differential equations with the derivative term contained in the nonlinear term

In this paper, based on the properties of Green function and the eigenvalue of a corresponding linear operator, the existence of positive solutions is investigated by spectral analysis for a infinite-points singular p-Laplacian Hadamard fractional differential equation boundary value problem, and an example is given to demonstrate the validity of our main results

Complete plastome sequence of Iodes cirrhosa Turcz., the first in the Icacinaceae, comparative genomic analyses and possible split of Idoes species in response to climate changes

Plastome-based phylogenetic study has largely resolved the phylogeny of Icacinaceae. However, no single complete plastome sequence is available for Icacinaceae species, thereby limiting the further phylogenomics analysis of the members of this family. Here, we obtained the complete plastome sequence of Iodes cirrhosa Turcz., which is the first in Icacinaceae, by using the next-generation sequencing technology. The genome was annotated and compared with other closely related plastomes by using mVISTA. The divergence time of six Iodes species was analyzed using the BEAST software. The plastome of I. cirrhosa was 151,994 bp long, with a pair of inverted repeats (IRs, 24,973 bp) separated by a large single-copy (LSC, 84,527 bp) region and a small single-copy (SSC, 17,521 bp) region. The plastome encoded 112 unique genes, including 80 protein-coding, 28 tRNA, and four rRNA genes. Approximately 59 repeat sequences and 188 simple sequence repeats were identified. Four pairs of partially overlapped genes, namely, psbD/psbC, ndhF/Ψycf1, atpB/atpE, and rpl22/rps3, were observed. A comparison of the boundaries of the LSC, SSC, and IR regions with four other plastomes from Aquifoliales and Sapindales exhibited a high overall degree of sequence similarity. Four most highly variable regions, namely, trnH-GUG/psbA, psbM/trnD-GUC, petA/psbJ, and rps16/trnQ-UUG, were found. Using the plastome of I. cirrhosa as reference, we reassembled the plastomes of five Iodes species. Ka/Ks ratio analyses revealed that 27 genes and 52 amino acid residue sites from 11 genes had undergone strong positive selection in the Iodes branch, with the most abundant proteins being the NDH and ribosomal proteins. Divergence-time analysis indicated that Iodes species were first formed 34.40 million years ago. Results revealed that the ancestor of the six species was likely to have split in the late Eocene epoch. In summary, the first complete plastome sequence of I. cirrhosa provided valuable information regarding the evolutionary processes of Iodes species

CpGAVAS, an integrated web server for the annotation, visualization, analysis, and GenBank submission of completely sequenced chloroplast genome sequences

Abstract Background The complete sequences of chloroplast genomes provide wealthy information regarding the evolutionary history of species. With the advance of next-generation sequencing technology, the number of completely sequenced chloroplast genomes is expected to increase exponentially, powerful computational tools annotating the genome sequences are in urgent need. Results We have developed a web server CPGAVAS. The server accepts a complete chloroplast genome sequence as input. First, it predicts protein-coding and rRNA genes based on the identification and mapping of the most similar, full-length protein, cDNA and rRNA sequences by integrating results from Blastx, Blastn, protein2genome and est2genome programs. Second, tRNA genes and inverted repeats (IR) are identified using tRNAscan, ARAGORN and vmatch respectively. Third, it calculates the summary statistics for the annotated genome. Fourth, it generates a circular map ready for publication. Fifth, it can create a Sequin file for GenBank submission. Last, it allows the extractions of protein and mRNA sequences for given list of genes and species. The annotation results in GFF3 format can be edited using any compatible annotation editing tools. The edited annotations can then be uploaded to CPGAVAS for update and re-analyses repeatedly. Using known chloroplast genome sequences as test set, we show that CPGAVAS performs comparably to another application DOGMA, while having several superior functionalities. Conclusions CPGAVAS allows the semi-automatic and complete annotation of a chloroplast genome sequence, and the visualization, editing and analysis of the annotation results. It will become an indispensible tool for researchers studying chloroplast genomes. The software is freely accessible from http://www.herbalgenomics.org/cpgavas

Sulfidation of Cadmium at the Nanoscale

We investigate the evolution of structures that result when spherical Cd nanoparticles of a few hundred nanometers in diameter react with dissolved molecular sulfur species in solution to form hollow CdS. Over a wide range of temperatures and concentrations, we find that rapid Cd diffusion through the growing CdS shell localizes the reaction front at the outermost CdS/S interface, leading to hollow particles when all the Cd is consumed. When we examine partially reacted particles, we find that this system differs significantly from others in which the nanoscale Kirkendall effect has been used to create hollow particles. In previously reported systems, partial reaction creates a hollow particle with a spherically symmetric metal core connected to the outer shell by filaments. In contrast, here we obtain a lower symmetry structure, in which the unreacted metal core and the coalesced vacancies separate into two distinct spherical caps, minimizing the metal/void interface. This pattern of void coalescence is likely to occur in situations where the metal/vacancy self-diffusivities in the core are greater than the diffusivity of the cations through the shell

A feature optimization study based on a diabetes risk questionnaire

IntroductionThe prevalence of diabetes, a common chronic disease, has shown a gradual increase, posing substantial burdens on both society and individuals. In order to enhance the effectiveness of diabetes risk prediction questionnaires, optimize the selection of characteristic variables, and raise awareness of diabetes risk among residents, this study utilizes survey data obtained from the risk factor monitoring system of the Centers for Disease Control and Prevention in the United States.MethodsFollowing univariate analysis and meticulous screening, a more refined dataset was constructed. This dataset underwent preprocessing steps, including data distribution standardization, the application of the Synthetic Minority Oversampling Technique (SMOTE) in combination with the Round function for equilibration, and data standardization. Subsequently, machine learning (ML) techniques were employed, utilizing enumerated feature variables to evaluate the strength of the correlation among diabetes risk factors.ResultsThe research findings effectively delineated the ranking of characteristic variables that significantly influence the risk of diabetes. Obesity emerges as the most impactful factor, overshadowing other risk factors. Additionally, psychological factors, advanced age, high cholesterol, high blood pressure, alcohol abuse, coronary heart disease or myocardial infarction, mobility difficulties, and low family income exhibit correlations with diabetes risk to varying degrees.DiscussionThe experimental data in this study illustrate that, while maintaining comparable accuracy, optimization of questionnaire variables and the number of questions can significantly enhance efficiency for subsequent follow-up and precise diabetes prevention. Moreover, the research methods employed in this study offer valuable insights into studying the risk correlation of other diseases, while the research results contribute to heightened societal awareness of populations at elevated risk of diabetes

Unlocking the mystery of the hard-to-sequence phage genome: PaP1 methylome and bacterial immunity

BACKGROUND: Whole-genome sequencing is an important method to understand the genetic information, gene function, biological characteristics and survival mechanisms of organisms. Sequencing large genomes is very simple at present. However, we encountered a hard-to-sequence genome of Pseudomonas aeruginosa phage PaP1. Shotgun sequencing method failed to complete the sequence of this genome. RESULTS: After persevering for 10 years and going over three generations of sequencing techniques, we successfully completed the sequence of the PaP1 genome with a length of 91,715 bp. Single-molecule real-time sequencing results revealed that this genome contains 51 N-6-methyladenines and 152 N-4-methylcytosines. Three significant modified sequence motifs were predicted, but not all of the sites found in the genome were methylated in these motifs. Further investigations revealed a novel immune mechanism of bacteria, in which host bacteria can recognise and repel modified bases containing inserts in a large scale. This mechanism could be accounted for the failure of the shotgun method in PaP1 genome sequencing. This problem was resolved using the nfi(-) mutant of Escherichia coli DH5α as a host bacterium to construct a shotgun library. CONCLUSIONS: This work provided insights into the hard-to-sequence phage PaP1 genome and discovered a new mechanism of bacterial immunity. The methylome of phage PaP1 is responsible for the failure of shotgun sequencing and for bacterial immunity mediated by enzyme Endo V activity; this methylome also provides a valuable resource for future studies on PaP1 genome replication and modification, as well as on gene regulation and host interaction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-803) contains supplementary material, which is available to authorized users

Addition of Risk-enhancing Factors Improves Risk Assessment of Atherosclerotic Cardiovascular Disease in Middle-aged and Older Chinese Adults: Findings from the Chinese Multi-provincial Cohort Study

Objective: This study aimed to examine whether integrating risk-enhancing factors into the Chinese Society of Cardiology-recommended clinical risk assessment tool (i.e., the CSC model) for atherosclerotic cardiovascular disease (ASCVD) might improve 10-year ASCVD risk stratification in Chinese adults. Methods: A total of 4910 Chinese participants who were 50–79 years of age and free of cardiovascular disease in the 2007–2008 Survey from the Chinese Multi-provincial Cohort Study were included. We assessed the updated model’s clinical utility (i.e., Harrell’s C-index and net reclassification improvement [NRI]) by adding risk-enhancing factors individually or the number of risk-enhancing factors to the CSC model, for all individuals or those at intermediate risk. Risk-enhancing factors, including a family history of CVD, triglycerides ≥2.3 mmol/L, high-sensitivity C-reactive protein ≥2 mg/L, Lipoprotein (a) ≥50 mg/dL, non-high-density lipoprotein cholesterol ≥4.9 mmol/L, overweight/obesity, and central obesity, were evaluated. ASCVD events were defined as a composite endpoint comprising ischemic stroke and acute coronary heart disease events (including nonfatal acute myocardial infarction and all coronary deaths). Results: During a median 10-year follow-up, 449 (9.1%) ASCVD events were recorded. Addition of ≥2 risk-enhancing factors to the CSC model yielded a significant improvement in the C-index (1.0%, 95% confidence interval [CI]: 0.2–1.7%) and a modest improvement in the NRI (2.0%, 95% CI: −1.2–5.4%) in the total population. For intermediate-risk individuals, particularly individuals at high risk of developing ASCVD, significant improvements in NRI were observed after adding ≥2 risk-enhancing factors (17.4%, 95% CI: 5.6–28.5%) to the CSC model. Conclusions: Addition of ≥2 risk-enhancing factors refined 10-year ASCVD risk stratification, particularly for intermediate-risk individuals, supporting their potential in helping tailor targeted interventions in clinical practice