Role of the SaeRS two-component regulatory system in Staphylococcus epidermidis autolysis and biofilm formation

<p>Abstract</p> <p>Background</p> <p><it>Staphylococcus epidermidis </it>(SE) has emerged as one of the most important causes of nosocomial infections. The SaeRS two-component signal transduction system (TCS) influences virulence and biofilm formation in <it>Staphylococcus aureus</it>. The deletion of <it>saeR </it>in <it>S. epidermidis </it>results in impaired anaerobic growth and decreased nitrate utilization. However, the regulatory function of SaeRS on biofilm formation and autolysis in <it>S. epidermidis </it>remains unclear.</p> <p>Results</p> <p>The <it>saeRS </it>genes of SE1457 were deleted by homologous recombination. The <it>saeRS </it>deletion mutant, SE1457<it>ΔsaeRS</it>, exhibited increased biofilm formation that was disturbed more severely (a 4-fold reduction) by DNase I treatment compared to SE1457 and the complementation strain SE1457<it>saec</it>. Compared to SE1457 and SE1457<it>saec</it>, SE1457<it>ΔsaeRS </it>showed increased Triton X-100-induced autolysis (approximately 3-fold) and decreased cell viability in planktonic/biofilm states; further, SE1457<it>ΔsaeRS </it>also released more extracellular DNA (eDNA) in the biofilms. Correlated with the increased autolysis phenotype, the transcription of autolysis-related genes, such as <it>atlE </it>and <it>aae</it>, was increased in SE1457<it>ΔsaeRS</it>. Whereas the expression of accumulation-associated protein was up-regulated by 1.8-fold in 1457<it>ΔsaeRS</it>, the expression of an N-acetylglucosaminyl transferase enzyme (encoded by <it>icaA</it>) critical for polysaccharide intercellular adhesin (PIA) synthesis was not affected by the deletion of <it>saeRS.</it></p> <p>Conclusions</p> <p>Deletion of <it>saeRS </it>in <it>S. epidermidis </it>resulted in an increase in biofilm-forming ability, which was associated with increased eDNA release and up-regulated Aap expression. The increased eDNA release from SE1457<it>ΔsaeRS </it>was associated with increased bacterial autolysis and decreased bacterial cell viability in the planktonic/biofilm states.</p

Stimuli-responsive crosslinked nanomedicine for cancer treatment.

Nanomedicines are attractive paradigms to deliver drugs, contrast agents, immunomodulators, and gene editors for cancer therapy and diagnosis. However, the currently developed nanomedicine suffers from poor serum stability, premature drug release, and lack of responsiveness. Crosslinking strategy can be utilized to overcome these shortcomings by employing stimuli-responsive chemical bonds to tightly hold the nanostructure and releasing the payloads spatiotemporally in a highly controlled manner. In this Review, we summarize the recently ingenious design of the stimuli-responsive crosslinked nanomedicines (SCN) in the field of cancer treatment and their advances in circumventing the drawbacks of the conventional drug delivery system. We classify the SCNs into three categories based on the crosslinking strategies, including built-in, on-surface, and inter-particle crosslinking nanomedicines. Thanks to the stimuli-responsive crosslinkages, SCNs are capable of keeping robust stability during systemic circulation. They also respond to the particular tumoral conditions to experience a series of dynamic changes, such as the changes in size, surface charge, targeting moieties, integrity, and imaging signals. These characteristics allow them to efficiently overcome different biological barriers and substantially improve the drug delivery efficiency, tumor-targeting ability, and imaging sensitivities. With the examples discussed, we envision that our perspectives can inspire more attempts to engineer intelligent nanomedicine to achieve effective cancer therapy and diagnosis

Insertion/Deletion Within the KDM6A Gene Is Significantly Associated With Litter Size in Goat

A previous whole-genome association analysis identified lysine demethylase 6A (KDM6A), which encodes a type of histone demethylase, as a candidate gene associated to goat fecundity. KDM6A gene knockout mouse disrupts gametophyte development, suggesting that it has a critical role in reproduction. In this study, goat KDM6A mRNA expression profiles were determined, insertion/deletion (indel) variants in the gene identified, indel variants effect on KDM6A gene expression assessed, and their association with first-born litter size analyzed in 2326 healthy female Shaanbei white cashmere goats. KDM6A mRNA was expressed in all tissues tested (heart, liver, spleen, lung, kidney, muscle, brain, skin and testis); the expression levels in testes at different developmental stages [1-week-old (wk), 2, 3 wk, 1-month-old (mo), 1.5 and 2 mo] indicated a potential association with the mitosis-to-meiosis transition, implying that KDM6A may have an essential role in goat fertility. Meanwhile, two novel intronic indels of 16 bp and 5 bp were identified. Statistical analysis revealed that only the 16 bp indel was associated with first-born litter size (P &lt; 0.01), and the average first-born litter size of individuals with an insertion/insertion genotype higher than that of those with the deletion/deletion genotype (P &lt; 0.05). There was also a significant difference in genotype distributions of the 16 bp indel between mothers of single-lamb and multi-lamb litters in the studied goat population (P = 0.001). Consistently, the 16 bp indel also had a significant effect on KDM6A gene expression. Additionally, there was no significant linkage disequilibrium (LD) between these two indel loci, consistent with the association analysis results. Together, these findings suggest that the 16 bp indel in KDM6A may be useful for marker-assisted selection (MAS) of goats

Bacterial Cellulose: A Versatile Chiral Host for Circularly Polarized Luminescence

Materials capable of circularly polarized luminescence (CPL) have attracted considerable attention for their promising potential applications. Bacterial cellulose (BC) was characterized as having a stable right-handed twist, which makes it a potential chiral host to endow luminophores with CPL. Then, the CPL-active BC composite film was constructed by simply impregnating bacterial cellulose pellicles with dilute aqueous solutions of luminophores (rhodamine B, carbon dots, polymer dots) and drying under ambient conditions. Simple encapsulation of luminophores renders BC with circularly polarized luminescence with a dissymmetry factor of up to 0.03. The multiple chiral centers of bacterial cellulose provide a primary asymmetric environment that can be further modulated by supramolecular chemistry, which is responsible for its circular polarization ability. We further demonstrate that commercial grade paper may endow luminophores with CPL activity, which reifies the universality of the method

Arbuscular Mycorrhizae Fungi Diversity in the Root–Rhizosphere–Soil of <i>Tetraena mongolica</i>, <i>Sarcozygium xanthoxylon</i>, and <i>Nitraria tangutorum</i> Bobr in Western Ordos, China

Arbuscular mycorrhizal fungi (AMF) are considered to be an essential indicator of ecosystem biodiversity and can increase a plant’s ability to withstand arid conditions. Despite the obvious significance of AMF in the root and rhizosphere system, little is known about how the AMF variety varies between the soil and roots of endangered plants and how this varies depending on habitats in dry and semiarid regions. This study aimed to address this research gap by investigating the characteristics and diversity of AMF colonization in Zygophyllaceae. Using Illumina MiSeq high-throughput sequencing, indigenous AMF in the roots and rhizosphere soil of three endangered plants (Tetraena mongolica, Sarcozygium xanthoxylon, and Nitraria tangutorum Bobr) were investigated. The three threatened plants had different AMF populations in their root and rhizosphere soils, according to a hierarchical clustering analysis. AMF communities in rhizosphere soil were more sensitive to LDA than root AMF communities based on linear discriminant analysis effect size (LEfSe). Glomus, Septoglomus, and Rhizophagus were seen to function as dominant fungi as the soil and root AMF populations carried out their various tasks in the soil and roots as a cohesive collective. Distance-based redundancy analysis (db-RDA) showed that pH, total phosphorus, and accessible potassium were closely associated with AMF communities. The pH of the soil appears to be an important factor in determining AMF community stability. These findings can serve as a guide for the use of AM fungus in the rehabilitation of agricultural land in arid regions. In summary, our work contributed new knowledge for the scientific preservation of these endangered plant species and for the further investigation of the symbiotic link between AMF and endangered plant species

A tumor-penetrable drug nanococktail made from human histones for interventional nucleus-targeted chemophotothermal therapy of drug-resistant tumors

Nanoparticle-based chemophotothermal therapy (CPT) is a promising treatment for multidrug resistant tumors. In this study, a drug nanococktail of DIR825@histone was developed by employing doxorubicin (DOX), NIR dye IR825 and human histones for interventional nucleus-targeted CPT of multidrug resistant tumors with an interventional laser. After localized intervention, DIR825@histone penetrated tumor tissues by transcytosis, efficiently entered tumor cells and targeted the cell nuclei. DIR825@histone also exhibited good photothermal performance and thermal-triggered drug release. Efficient multidrug resistant tumor inhibition was achieved by enhanced CPT sensitization and MDR reversion via nuclear targeting. Moreover, an interventional laser assisted DIR825@histone in inhibiting multidrug resistant tumors by promoting the sufficient delivery of laser energy inside the tumor while reducing skin injury. Therefore, DIR825@histone together with this interventional nucleus-targeted CPT strategy holds great promise for treating multidrug resistant tumors

Exploration of Genetic Variants within the Goat A-Kinase Anchoring Protein 12 (AKAP12) Gene and Their Effects on Growth Traits

The A-kinase anchoring protein 12 gene (AKAP12) is a scaffold protein, which can target multiple signal transduction effectors, can promote mitosis and cytokinesis and plays an important role in the regulation of growth and development. In our previous study, P1–7 bp (intron 3) and P2–13 bp (3′UTR) indels within the AKAP12 gene significantly influenced AKAP12 gene expression. Therefore, this study aimed to identify the association between these two genetic variations and growth-related traits in Shaanbei white cashmere goats (SBWC) (n = 1405). Herein, we identified two non-linkage insertions/deletions (indels). Notably, we found that the P1–7 bp indel mutation was related to the height at hip cross (HHC; p &lt; 0.05) and the P2–13 bp indel was associated with body weight, body length, chest depth, chest width, hip width, chest circumference and cannon (bone) circumference in SBWC goats (p &lt; 0.05). Overall, the two indels’ mutations of AKAP12 affected growth traits in goats. Compared to the P1–7 bp indel, the P2–13 bp indel is more suitable for the breeding of goat growth traits