Charge-Determined LCST/UCST Behavior in Ionic Polypeptoids

Stimuli-responsive polymers have received increasing interest for a variety of applications. Here, we report a series of unique charge-determined thermoresponsive polypeptoids synthesized by a combination of ring-opening polymerization and click chemistry. The LCST-type and UCST-type behavior is mainly dominated by the charge state on the side chain. Further, the phase transition temperature highly depends on the degree of polymerization, the side-chain architecture, the pH value, and so on. The obtained polypeptoid solutions exhibit good stability against temperature and salt concentration. To our knowledge, this report presents the first charge-determined LCST/UCST-type polymer from identical homopolymer backbone that displays a wide range of tunable cloudy points in aqueous media. We propose the hydrogen-bonding interaction plays a critical part on the solution behavior. These features make polypeptoids ideal candidates for highly designable stimuli-responsive polymeric materials

Spherical Nucleic Acid Probe Based on 2′-Fluorinated DNA Functionalization for High-Fidelity Intracellular Sensing

Traditional spherical nucleic acids (SNAs) based on gold nanoparticles (AuNPs) assembled through Au–S covalent bonds are widely used in DNA-programmable assembly, biosensing, imaging, and therapeutics. However, biological thiols and other chemical substances can break the Au–S bonds and cause response distortion during the application process, specifically in cell environments. Herein, we report a new type of SNAs based on 2′-fluorinated DNA-functionalized AuNPs with excellent colloidal stability under high salt conditions (up to 1 M NaCl) and over a broad pH range (1–14), as well as resistance to biothiols. The fluorinated spherical nucleic acid probe (Au/FDNA probe) could detect targeted cancer cells with high fidelity. Compared to the traditional thiolated DNA-functionalized AuNP probe (Au–SDNA probe), the Au/FDNA probe exhibited a higher sensitivity to the target and a lower signal-to-background ratio. Furthermore, the Au/FDNA probe could discriminate target cancer cells in a mixed culture system. Using the proposed FDNA functionalization method, previously developed SNAs based on AuNPs could be directly adapted, which might open a new avenue for the design and application of SNAs

A Self-Assembled Copper-Selenocysteine Nanoparticle for Enhanced Chemodynamic Therapy via Oxidative Stress Amplification

Chemodynamic therapy (CDT) as a catalytic anticancer strategy utilizes transition metal ions to initiate the Fenton reaction to produce high levels of cytotoxic hydroxyl radicals(·OH) in situ. Nevertheless, current existing CDTs are normally restricted by the high levels of existing antioxidant molecules and/or enzymes, such as glutathione (GSH) and thioredoxin reductase (TrxR), in a tumor internal environment, which could suppress CDT via ·OH depletion. Herein, to enhance ·OH-induced cellular damage by CDT, a self-assembled copper-selenocysteine nanoparticles (Cu-SeC NPs) was fabricated through a one-pot process. In our design, once Cu-SeC NPs were endocytosed by tumor cells, Cu2+ was reduced to Cu+ by cellular GSH, promoting in situ Fenton-like reactions to trigger ·OH rapid production in cells as well as the depletion of GSH. Furthermore, the gradually released selenocysteine can inhibit TrxR activity to weaken the protection of antioxidant systems and provide a favorable microenvironment for CDT. As a result, both paths synergistically resulted in massive reactive oxygen species (ROS) accumulation and amplified oxidative stress in tumor sites for enhanced CDT. As a new intelligent anticancer nanoplatform, Cu-SeC NPs exhibit synergistic antitumor effects with negligible systemic toxicity. Thus, the proposed strategy provides a new avenue for further development of progressive therapeutic systems

Supplemental_Table_and_figures - Thrombin Alters Human Endometrial Stromal Cell Differentiation During Decidualization

<p>Supplemental_Table_and_figures for Thrombin Alters Human Endometrial Stromal Cell Differentiation During Decidualization by Samir N. Babayev, Mohammed Kanchwala, Chao Xing, Yucel Akgul, Bruce R. Carr, and Ruth Ann Word in Reproductive Sciences</p

Genome-Wide Association Analysis of Radiation Resistance in <i>Drosophila melanogaster</i>

<div><p>Background</p><p>Ionizing radiation is genotoxic to cells. Healthy tissue toxicity in patients and radiation resistance in tumors present common clinical challenges in delivering effective radiation therapies. Radiation response is a complex, polygenic trait with unknown genetic determinants. The <i>Drosophila</i> Genetic Reference Panel (DGRP) provides a model to investigate the genetics of natural variation for sensitivity to radiation.</p><p>Methods and Findings</p><p>Radiation response was quantified in 154 inbred DGRP lines, among which 92 radiosensitive lines and 62 radioresistant lines were classified as controls and cases, respectively. A case-control genome-wide association screen for radioresistance was performed. There are 32 single nucleotide polymorphisms (SNPs) associated with radio resistance at a nominal <i>p</i><10⁻⁵; all had modest effect sizes and were common variants with the minor allele frequency >5%. All the genes implicated by those SNP hits were novel, many without a known role in radiation resistance and some with unknown function. Variants in known DNA damage and repair genes associated with radiation response were below the significance threshold of <i>p</i><10⁻⁵ and were not present among the significant hits. No SNP met the genome-wide significance threshold (<i>p</i> = 1.49×10⁻⁷), indicating a necessity for a larger sample size.</p><p>Conclusions</p><p>Several genes not previously associated with variation in radiation resistance were identified. These genes, especially the ones with human homologs, form the basis for exploring new pathways involved in radiation resistance in novel functional studies. An improved DGRP model with a sample size of at least 265 lines and ideally up to 793 lines is recommended for future studies of complex traits.</p></div

Odds ratio histogram of top 32 SNPs at p<10⁻⁵.

<p>Odds ratio histogram of top 32 SNPs at p<10⁻⁵.</p

Association analyses of radiation resistance among 154 DGRP lines.

<p>(A) Quantile-quantile plot. The red line indicates the expected and the black line the observed <i>p</i> values. (B) Manhattan plot of <i>p</i> values. The red dashed line indicates <i>p</i><10⁻⁵.</p

Urinary Glycosaminoglycans Are Associated with Recurrent UTI and Urobiome Ecology in Postmenopausal Women

Glycosaminoglycans (GAGs) are linear, negatively charged polysaccharides composed of repeating disaccharide units of uronic acid and amino sugars. The luminal surface of the bladder epithelium is coated with a GAG layer. These urothelial GAGs are thought to provide a protective barrier and serve as a potential interaction site with the urinary microbiome (urobiome). Previous studies have profiled urinary GAG composition in mixed cohorts, but the urinary GAG composition in postmenopausal women remains undefined. To investigate the relationship between GAGs and recurrent urinary tract infection (rUTI), we profiled urinary GAGs in a controlled cohort of postmenopausal women. We found that chondroitin sulfate (CS) is the major urinary GAG in postmenopausal women and that urinary CS was elevated in women with active rUTI. We also associated urinary GAGs with urobiome composition and identified bacterial species that significantly associated with urinary GAG concentration. Corynebacterium amycolatum, Porphyromonas somerae, and Staphylococcus pasteuri were positively associated with heparin sulfate or hyaluronic acid, and bacterial species associated with vaginal dysbiosis were negatively correlated with urinary CS. Altogether, this work defines changes in urinary GAG composition associated with rUTI and identifies new associations between urinary GAGs and the urobiome that may play a role in rUTI pathobiology

Sex-stratified analysis of <i>NOS1AP</i> SNPs for association with QT interval.

<p>The “Δ Effect Size” indicates the effect size in males subtracted from that observed in females. Hence a positive value indicates a larger effect in women. Effect sizes are in ms, and are per allele under an additive genetic model.</p

Urinary Glycosaminoglycans Are Associated with Recurrent UTI and Urobiome Ecology in Postmenopausal Women

Glycosaminoglycans (GAGs) are linear, negatively charged polysaccharides composed of repeating disaccharide units of uronic acid and amino sugars. The luminal surface of the bladder epithelium is coated with a GAG layer. These urothelial GAGs are thought to provide a protective barrier and serve as a potential interaction site with the urinary microbiome (urobiome). Previous studies have profiled urinary GAG composition in mixed cohorts, but the urinary GAG composition in postmenopausal women remains undefined. To investigate the relationship between GAGs and recurrent urinary tract infection (rUTI), we profiled urinary GAGs in a controlled cohort of postmenopausal women. We found that chondroitin sulfate (CS) is the major urinary GAG in postmenopausal women and that urinary CS was elevated in women with active rUTI. We also associated urinary GAGs with urobiome composition and identified bacterial species that significantly associated with urinary GAG concentration. Corynebacterium amycolatum, Porphyromonas somerae, and Staphylococcus pasteuri were positively associated with heparin sulfate or hyaluronic acid, and bacterial species associated with vaginal dysbiosis were negatively correlated with urinary CS. Altogether, this work defines changes in urinary GAG composition associated with rUTI and identifies new associations between urinary GAGs and the urobiome that may play a role in rUTI pathobiology