Hydrogen Clouds before Reionization: a Lognormal Model Approach

We study the baryonic gas clouds (the IGM) in the universe before the reionization with the lognormal model which is shown to be dynamcially legitimate in describing the fluctuation evolution in quasilinear as well as nonlinear regimes in recent years. The probability distribution function of the mass field in the LN model is long tailed and so plays an important role in rare events, such as the formation of the first generation of baryonic objects. We calculate density and velocity distributions of the IGM at very high spatial resolutions, and simulate the distributions at resolution of 0.15 kpc from z=7 to 15 in the LCDM cosmological model. We performed a statistics of the hydrogen clouds including column densities, clumping factors, sizes, masses, and spatial number density etc. One of our goals is to identify which hydrogen clouds are going to collapse. By inspecting the mass density profile and the velocity profile of clouds, we found that the velocity outflow significantly postpones the collapsing process in less massive clouds, in spite of their masses are larger than the Jeans mass. Consequently, only massive (> 10^5 M_sun) clouds can form objects at higher redshift, and less massive (10^4-10^5) collapsed objects are formed later. For example, although the mass fraction in clouds with sizes larger than the Jeans length is already larger than 1 at z=15, there is only a tiny fraction of mass (10^{-8}) in the clouds which are collapsed at that time. If all the ionizing photons, and the 10^{-2} metallicity observed at low redshift are produced by the first 1% mass of collapsed baryonic clouds, the majority of those first generation objects would not happen until z=10.Comment: Paper in AAStex, 12 figure

Serum phosphate levels and the development of sepsis associated acute kidney injury: evidence from two independent databases

ObjectiveWe aimed to investigate the association between serum phosphate levels and the risk for developing sepsis associated acute kidney injury (SAKI).MethodsSeptic patients from the Medical Information Mart for Intensive Care IV (MIMIC IV) and the eICU Collaborative Research Database (eICU-CRD) were enrolled. Restricted cubic spline (RCS) was used to visualize the relationship between phosphate levels and the risk of SAKI. Patients were divided into four categories based on their serum phosphate levels. Logistic regression analysis, receiver operating characteristic (ROC) curve and subgroup analysis were performed to evaluate the predictive value of serum phosphate for SAKI.ResultsA total of 9,244 and 2,124 patients from the MIMIC IV and eICU-CRD database were included in the final analysis. RCS curve revealed a non-linear correlation between phosphate levels and the risk of SAKI (p for non-linearity <0.05). Each 1 mg/dL increase in phosphate levels was associated with a 1.51 to 1.64-fold increased risk of SAKI (OR 2.51–2.64, p < 0.001) in the MIMIC IV cohort and a 0.29 to 0.38-fold increased risk (OR 1.29–1.38, p < 0.001) in the eICU-CRD cohort. Compared to the normal-low category, hyperphosphatemia and normal-high category were independently associated with an increased risk of SAKI, while hypophosphatemia was independently associated with a decreased risk in the MIMIC IV cohort. A similar trend was observed in the eICU-CRD cohort, but statistical significance disappeared in the hypophosphatemia category and the adjusted model of normal high category. These finding was consistent in subgroup analysis.ConclusionElevated serum phosphate, even within the normal range, is an independent risk factor for developing SAKI in septic patients. Abnormal change in serum phosphate levels may be a novel biomarker for early prediction of SAKI occurrence

Determination of Optical Density (OD) of Oligodeoxynucleotide from HPLC Peak Area

Oligodeoxynucleotides (ODNs) are typically purified and analysed with HPLC equipped with a UV-Vis detector. Quantities of ODNs are usually determined using a UV-Vis spectrometer separately after HPLC, and are reported as optical density at 260 nm (OD260). Here, we describe a method for direct determination of OD260 of ODNs using the area of the peaks in HPLC profiles

Long oligos: direct chemical synthesis of genes with up to 1728 nucleotides

The longest oligos that can be chemically synthesized are considered to be 200-mers. Here, we report direct synthesis of an 800-mer green fluorescent protein gene and a 1728-mer Φ29 DNA polymerase gene on an automated synthesizer. Key innovations that enabled this breakthrough include conducting the synthesis on a smooth surface rather than within the pores of traditional supports, and the use of the powerful catching-by-polymerization (CBP) method for isolating the full-length oligos from a complex mixture. Conducting synthesis on a smooth surface not only eliminated the steric hindrance that would otherwise prevent long oligo assembly, but also, surprisingly, drastically reduced synthesis errors. Compared with the benchmark PCR assembly gene synthesis method, the direct long oligo synthesis method has the advantages of higher probability to succeed, fewer sequence restrictions, and being able to synthesize long oligos containing difficult elements such as unusually stable higher-order structures, long repeats, and site-specific modifications. The method is expected to open doors for various projects in areas such as synthetic biology, gene editing, and protein engineering

Niaoduqing alleviates podocyte injury in high glucose model via regulating multiple targets and AGE/RAGE pathway: Network pharmacology and experimental validation

Purpose: The aim of present study was to explore the pharmacological mechanisms of Niaoduqing granules on the treatment of podocyte injury in diabetic nephropathy (DN) via network pharmacology and experimental validation.Methods: Active ingredients and related targets of Niaoduqing, as well as related genes of podocyte injury, proteinuria and DN, were obtained from public databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis were performed to investigate the potential mechanisms. High glucose (HG) -induced MPC5 cell injury model was treated with the major core active ingredients of Niaoduqing and used to validate the predicted targets and signaling pathways.Results: Totally, 16 potential therapeutic targets were identified by intersecting the targets of Niaoduqing and disease, in which 7 of them were considered as the core targets via PPI network analysis. KEGG enrichment analysis showed that AGE-RAGE signaling pathway was identified as the most crucial signaling pathway. The results of in vitro experiments revealed that the treatment of Niaoduqing active ingredients significantly protected MPC5 cells from HG-induced apoptosis. Moreover, Niaoduqing could significantly attenuate the HG-induced activation of AGE-RAGE signaling pathway, whereas inhibited the over-expression of VEGF-A, ICAM-1, PTGS-2 and ACE in HG-induced MPC5 cells.Conclusion: Niaoduqing might protect against podocyte injury in DN through regulating the activity of AGE/RAGE pathway and expression of multiple genes. Further clinical and animal experimental studies are necessary to confirm present findings

Assessing the causal relationship between gut microbiota and diabetic nephropathy: insights from two-sample Mendelian randomization

BackgroundThe causal association between gut microbiota (GM) and the development of diabetic nephropathy (DN) remains uncertain. We sought to explore this potential association using two-sample Mendelian randomization (MR) analysis.MethodsGenome-wide association study (GWAS) data for GM were obtained from the MiBioGen consortium. GWAS data for DN and related phenotypes were collected from the FinngenR9 and CKDGen databases. The inverse variance weighted (IVW) model was used as the primary analysis model, supplemented by various sensitivity analyses. Heterogeneity was assessed using Cochran’s Q test, while horizontal pleiotropy was evaluated through MR-Egger regression and the MR-PRESSO global test. Reverse MR analysis was conducted to identify any reverse causal effects.ResultsOur analysis identified twenty-five bacterial taxa that have a causal association with DN and its related phenotypes (p < 0.05). Among them, only the g_Eubacterium_coprostanoligenes_group showed a significant causal association with type 1 DN (p < Bonferroni-adjusted p-value). Our findings remained consistent regardless of the analytical approach used, with all methods indicating the same direction of effect. No evidence of heterogeneity or horizontal pleiotropy was observed. Reverse MR analysis did not reveal any causal associations.ConclusionsThis study established a causal association between specific GM and DN. Our findings contribute to current understanding of the role of GM in the development of DN, offering potential insights for the prevention and treatment strategies for this condition

Deep unfolding Network for Hyperspectral Image Super-Resolution with Automatic Exposure Correction

In recent years, the fusion of high spatial resolution multispectral image (HR-MSI) and low spatial resolution hyperspectral image (LR-HSI) has been recognized as an effective method for HSI super-resolution (HSI-SR). However, both HSI and MSI may be acquired under extreme conditions such as night or poorly illuminating scenarios, which may cause different exposure levels, thereby seriously downgrading the yielded HSISR. In contrast to most existing methods based on respective low-light enhancements (LLIE) of MSI and HSI followed by their fusion, a deep Unfolding HSI Super-Resolution with Automatic Exposure Correction (UHSR-AEC) is proposed, that can effectively generate a high-quality fused HSI-SR (in texture and features) even under very imbalanced exposures, thanks to the correlation between LLIE and HSI-SR taken into account. Extensive experiments are provided to demonstrate the state-of-the-art overall performance of the proposed UHSR-AEC, including comparison with some benchmark peer methods

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

Long oligodeoxynucleotides (ODNs) are segments of DNAs having over one hundred nucleotides (nt). They are typically assembled using enzymatic methods such as PCR and ligation from shorter 20 to 60 nt ODNs produced by automated de novo chemical synthesis. While these methods have made many projects in areas such as synthetic biology and protein engineering possible, they have various drawbacks. For example, they cannot produce genes and genomes with long repeats and have difficulty to produce sequences containing stable secondary structures. Here, we report a direct de novo chemical synthesis of 400 nt ODNs, and their isolation from the complex reaction mixture using the catching-by-polymerization (CBP) method. To determine the authenticity of the ODNs, 399 and 401 nt ODNs were synthesized and purified with CBP. The two were joined together using Gibson assembly to give the 800 nt green fluorescent protein (GFP) gene construct. The sequence of the construct was verified via Sanger sequencing. To demonstrate the potential use of the long ODN synthesis method, the GFP gene was expressed in E. coli. The long ODN synthesis and isolation method presented here provides a pathway to the production of genes and genomes containing long repeats or stable secondary structures that cannot be produced or are highly challenging to produce using existing technologies