CpG island density and its correlations with genomic features in mammalian genomes

A systematic analysis of CpG islands in ten mammalian genomes suggests that an increase in chromosome number elevates GC content and prevents loss of CpG islands

Simultaneous saccharification of hemicellulose and cellulose of corncob in a one-pot system using catalysis of carbon based solid acid from lignosulfonate

The drive towards sustainable chemistry has inspired the development of active solid acids as catalysts and ionic liquids as solvents for an efficient release of sugars from lignocellulosic biomass for future biorefinery practices. Carbon-based solid acid (SI–C–S–H2O2) prepared from sodium lignosulfonate, a waste of the paper industry, was used with water or ionic liquid to hydrolyze corncob in this study. The effects of various reaction parameters were investigated in different solvent systems. The highest xylose yield of 83.4% and hemicellulose removal rate of 90.6% were obtained in an aqueous system at 130 °C for 14 h. After the pretreatment, cellulase was used for the hydrolysis of residue and the enzymatic digestibility of 92.6% was obtained. Following these two hydrolysis steps in the aqueous systems, the highest yield of total reducing sugar (TRS) was obtained at 88.1%. Further, one-step depolymerization and saccharification of corncob hemicellulose and cellulose to reducing sugars in an IL-water system catalyzed by SI–C–S–H2O2 was conducted at 130 °C for 10 h, with a high TRS yield of 75.1% obtained directly. After recycling five times, the solid acid catalyst still showed a high catalytic activity for sugar yield in different systems, providing a green and effective method for lignocellulose degradation

Large-scale prediction of adverse drug reactions using chemical, biological, and phenotypic properties of drugs

Abstract Objective Adverse drug reaction (ADR) is one of the major causes of failure in drug development. Severe ADRs that go undetected until the post-marketing phase of a drug often lead to patient morbidity. Accurate prediction of potential ADRs is required in the entire life cycle of a drug, including early stages of drug design, different phases of clinical trials, and post-marketing surveillance. Methods Many studies have utilized either chemical structures or molecular pathways of the drugs to predict ADRs. Here, the authors propose a machine-learning-based approach for ADR prediction by integrating the phenotypic characteristics of a drug, including indications and other known ADRs, with the drug's chemical structures and biological properties, including protein targets and pathway information. A large-scale study was conducted to predict 1385 known ADRs of 832 approved drugs, and five machine-learning algorithms for this task were compared. Results This evaluation, based on a fivefold cross-validation, showed that the support vector machine algorithm outperformed the others. Of the three types of information, phenotypic data were the most informative for ADR prediction. When biological and phenotypic features were added to the baseline chemical information, the ADR prediction model achieved significant improvements in area under the curve (from 0.9054 to 0.9524), precision (from 43.37% to 66.17%), and recall (from 49.25% to 63.06%). Most importantly, the proposed model successfully predicted the ADRs associated with withdrawal of rofecoxib and cerivastatin. Conclusion The results suggest that phenotypic information on drugs is valuable for ADR prediction. Moreover, they demonstrate that different models that combine chemical, biological, or phenotypic information can be built from approved drugs, and they have the potential to detect clinically important ADRs in both preclinical and post-marketing phases.This study was supported in part by grants from the NHLBI 5U19HL065962 and the NCI R01CA141307. ML is supported by the NLM training grant 3T15LM007450-08S1. JS is partially supported by the 2010 NARSAD Young Investigator Award. ZZ is partially supported by the 2009 NARSAD Maltz Investigator Award. MM is supported by a Veterans Administration HSR&D Career Development Award (CDA-08-020)

Soil Moisture Availability at Early Growth Stages Strongly Affected Root Growth of Bothriochloa ischaemum When Mixed With Lespedeza davurica

Rainfall is the main resource of soil moisture in the semiarid areas, and the altered rainfall pattern would greatly affect plant growth and development. Root morphological traits are critical for plant adaptation to changeable soil moisture. This study aimed to clarify how root morphological traits of Bothriochloa ischaemum (a C4 herbaceous species) and Lespedeza davurica (a C3 leguminous species) in response to variable soil moisture in their mixtures. The two species were co-cultivated in pots at seven mixture ratios under three soil water regimes [80% (HW), 60% (MW), and 40% (LW) of soil moisture field capacity (FC)]. At the jointing, flowering, and filling stages of B. ischaemum, the LW and MW treatments were rewatered to MW or HW, respectively. At the end of growth season, root morphological traits of two species were evaluated. Results showed that the root morphological response of B. ischaemum was more sensitive than that of L. davurica under rewatering. The total root length (TRL) and root surface area (RSA) of both species increased as their mixture ratio decreased, which suggested that mixed plantation of the two species would be beneficial for their own root growth. Among all treatments, the increase of root biomass (RB), TRL, and RSA reached the highest levels when soil water content increased from 40 to 80% FC at the jointing stage. Our results implied that species-specific response in root morphological traits to alternated rainfall pattern would greatly affect community structure, and large rainfall occurring at early growth stages would greatly increase their root growth in the semiarid environments

Two-fold symmetric superconductivity in the kagome superconductor RbV3Sb5

The recent discovered kagome superconductors provide a good platform for studying intertwined orders and novel states such as topology, superconductor, charge density wave, et al. The interplay of these orders may spontaneously break the rotational symmetry, and induce exotic phenomena such as nematicity, or even nematic superconductor. Here we report a two-fold rotational symmetric superconductivity of thin-film RbV3Sb5 in response to a direction-dependent in-plane magnetic fields, in contrast to the six-fold structural symmetry of the crystal lattice. The two-fold symmetry was evidenced by the magnetoresistance transport experiments, critical magnetic field measurements and the anisotropic superconducting gap. With different configuration, we further observed the six-fold symmetry superimposed on the two-fold symmetry near the boundary between normal states and superconducting states. Our results present the correlation-driven symmetry breaking and highlight the promising platform to study the intertwined orders such as unconventional superconductivity in this correlated kagome family

Facile Fabrication of Sandwich Structural Membrane With a Hydrogel Nanofibrous Mat as Inner Layer for Wound Dressing Application

A common problem existing in wound dressing is to integrate the properties of against water erosion while maintaining a high water-uptake capacity. To tackle this issue, we imbedded one layer of hydrogel nanofibrous mat into two hydrophobic nanofibrous mats, thereafter, the sandwich structural membrane (SSM) was obtained. Particularly, SSM is composed of three individual nanofibrous layers which were fabricated through sequential electrospinning technology, including two polyurethane/antibacterial agent layers, and one middle gelatin/rutin layer. The obtained SSM is characterized in terms of morphology, component, mechanical, and functional performance. In addition to the satisfactory antibacterial activity against Staphylococcus aureus and Escherichia coli, and antioxidant property upon scavenging DPPH free radicals, the obtained SSM also shows a desirable thermally regulated water vapor transmission rate. More importantly, such SSM can be mechanically stable and keep its intact morphology without appearance damage while showing a high water-absorption ratio. Therefore, the prepared sandwich structural membrane with hydrogel nanofibrous mat as inner layer can be expected as a novel wound dressing

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts