The XRE Family Transcriptional Regulator SrtR in Streptococcus suis Is Involved in Oxidant Tolerance and Virulence

Streptococcus suis is a zoonotic pathogen that harbors anti-oxidative stress genes, which have been reported to be associated with virulence. Serial passage has been widely used to obtain phenotypic variant strains to investigate the functions of important genes. In the present study, S. suis serotype 9 strain DN13 was serially passaged in mice 30 times. The virulence of a single colony from passage 10 (SS9-P10) was found to increase by at least 140-fold as indicated by LD50 values, and the increased virulence was stable for single colonies from passage 20 (SS0-P20) and 30 (SS0-P30). Compared to the parental strain, the mouse-adapted strains were more tolerant to oxidative and high temperature stress. Genome-wide analysis of nucleotide variations found that reverse mutations occurred in seven genes, as indicated by BLAST analysis. Three of the reverse mutation genes or their homologs in other bacteria were reported to be virulence-associated, including ideSsuis in S. suis, a homolog of malR of Streptococcus pneumoniae, and a homolog of the prepilin peptidase-encoding gene in Legionella pneumophila. However, these genes were not involved in the stress response. Another gene, srtR (stress response transcriptional regulator), encoding an XRE family transcriptional regulator, which had an internal stop in the parental strain, was functionally restored in the adapted strains. Further analysis of DN13 and SS9-P10-background srtR-knock-out and complementing strains supported the contribution of this gene to stress tolerance in vitro and virulence in mice. srtR and its homologs are widely distributed in Gram-positive bacteria including several important human pathogens such as Enterococcus faecium and Clostridioides difficile, indicating similar functions in these bacteria. Taken together, our study identified the first member of the XRE family of transcriptional regulators that is involved in stress tolerance and virulence. It also provides insight into the mechanism of enhanced virulence after serial passage in experimental animals

Developmental characteristics of fractures in deep tight sandstone reservoirs in the second Member of the Xujiahe Formation of Zhongjiang Gas Field

The development characteristics, scale and control factors of fractures are the core subjects of reservoir sweet spot prediction. The sandstone reservoir of the TX2 gas reservoir in the Zhongjiang Gas Field is a typical low porosity and low permeability tight reservoir with strong heterogeneity, but relatively high-quality reservoirs can be found in different well areas and well segments. In this paper, taking the second Member of the Xujiahe Formation (TX2) as an example, the control factors of fractures were systemically investigated via core observation, thin section, logging data, and fracture logging identifications. The results show that shear fractures are mainly developed in the cores, and they generally have high filling rate and poor effectiveness; microfractures can be found based on the vitrinite and cast thin section results. The intersection diagram (semi-quantitative) and the principal component and BP comprehensive identification (quantitative) methods can effectively identify different types of fractures. The combined application of principal component and BP comprehensive identification methods results in an 83.3 % fracture identification probability. Finally, we found that the development of fractures in TX2 is comprehensively affected by lithology, rock thickness, porosity, and faults

Water advancing and receding process as a liquid–vapor interface geometrical question

Existing wetting theories have difficulty accurately describing advancing/receding processes on micro-structured surfaces. A strategy is proposed to solve this problem by recognizing it as a liquid–vapor interface geometrical question. The wetting chip method is proposed to realize the microscopic observation of liquid–vapor interface variations. A wetting model based on the liquid–vapor interface shape (LVIS model) is established to describe the analytical relationships between the apparent contact angles, liquid–vapor interface radius, substrate geometry, and chemical nature of liquid. The LVIS model is divided into four typical time points and three transition stages, and its predictions agree with the experimental measurements. In contrast to traditional theories, the apparent contact angles in a quasi-equilibrium state should be separated into advancing and receding processes, and in this state, apparent contact angles vary with changes in the parameters of micro-pillar width and spacing. This strategy has the potential to accurately describe the wetting process on micro-structure surfaces

Pooled analysis of routine safety parameters observed in healthy participants at baseline and following placebo administration in early phase clinical studies

Abstract Phase I trials inform on the initial safety profile of a new molecule and impact whether further development is pursued or not. Understanding the effect of non‐pharmacological factors on the variability of routine safety parameters could improve decision making in these early clinical trials, helping to separate signals related to the new molecule from background “noise.” To understand the impact of non‐pharmacological factors on routine safety parameters, we evaluated pooled safety data from over 1000 healthy participants treated with placebo in phase I trials between 2009 and 2018. The phase I participants were predominantly men, less than or equal to 50 years, White, and non‐Hispanic; and approximately an equal proportion had body mass index in the normal and overweight/obese range. Following administration of placebo, vital signs, electrocardiogram, and laboratory parameters remained near predose baseline values. Large changes from baseline were observed for many safety parameters, but these occurred in a relatively small number of participants. At least one adverse event (AE) occurred in 49.7% of participants receiving placebo in single ascending dose (SAD) studies and in 72.4% of participants receiving placebo in multiple ascending dose (MAD) studies, with headache being the most commonly reported AE (18.7% in SAD and 28.3% in MAD studies). Overall, these analyses are consistent with non‐pharmacological factors having a small impact on routine safety parameters in a phase I trial. The provided supplemental data may be used to contextualize the magnitude and frequency of abnormal safety values and AEs observed in phase I trials

Composite Structure Based on Gold-Nanoparticle Layer and HMM for Surface-Enhanced Raman Spectroscopy Analysis

Hyperbolic metamaterials (HMMs), supporting surface plasmon polaritons (SPPs), and highly confined bulk plasmon polaritons (BPPs) possess promising potential for application as surface-enhanced Raman scattering (SERS) substrates. In the present study, a composite SERS substrate based on a multilayer HMM and gold-nanoparticle (Au-NP) layer was fabricated. A strong electromagnetic field was generated at the nanogaps of the Au NPs under the coupling between localized surface plasmon resonance (LSPR) and a BPP. Additionally, a simulation of the composite structure was assessed using COMSOL; the results complied with those achieved through experiments: the SERS performance was enhanced, while the enhancing rate was downregulated, with the extension of the HMM periods. Furthermore, this structure exhibited high detection performance. During the experiments, rhodamine 6G (R6G) and malachite green (MG) acted as the probe molecules, and the limits of detection of the SERS substrate reached 10−10 and 10−8 M for R6G and MG, respectively. Moreover, the composite structure demonstrated prominent reproducibility and stability. The mentioned promising results reveal that the composite structure could have extensive applications, such as in biosensors and food safety inspection

Microdeletion in distal PLP1 enhancers causes hereditary spastic paraplegia 2

Abstract Objectives Hereditary spastic paraplegia (HSP) is a genetically heterogeneous disease caused by over 70 genes, with a significant number of patients still genetically unsolved. In this study, we recruited a suspected HSP family characterized by spasticity, developmental delay, ataxia and hypomyelination, and intended to reveal its molecular etiology by whole exome sequencing (WES) and long‐read sequencing (LRS) analyses. Methods WES was performed on 13 individuals of the family to identify the causative mutations, including analyses of SNVs (single‐nucleotide variants) and CNVs (copy number variants). Accurate circular consensus (CCS) long‐read sequencing (LRS) was used to verify the findings of CNV analysis from WES. Results SNVs analysis identified a missense variant c.195G>T (p.E65D) of MORF4L2 at Xq22.2 co‐segregating in this family from WES data. Further CNVs analysis revealed a microdeletion, which was adjacent to the MORF4L2 gene, also co‐segregating in this family. LRS verified this microdeletion and confirmed the deletion range (chrX: 103,690,507–103,715,018, hg38) with high resolution at nucleotide level accuracy. Interpretations In this study, we identified an Xq22.2 microdeletion (about 24.5 kb), which contains distal enhancers of the PLP1 gene, as a likely cause of SPG2 in this family. The lack of distal enhancers may result in transcriptional repression of PLP1 in oligodendrocytes, potentially affecting its role in the maintenance of myelin, and causing SPG2 phenotype. This study has highlighted the importance of noncoding genomic alterations in the genetic etiology of SPG2

MOESM1 of Isolation of nontuberculous mycobacteria from soil using Middlebrook 7H10 agar with increased malachite green concentration

Additional file 1. Additional material