Synthesis and Thermoresponsive Behaviors of Thermo‑, pH‑, CO₂‑, and Oxidation-Responsive Linear and Cyclic Graft Copolymers

Rational macromolecular design allows us to construct multiresponsive architectural polymers with a potential toward multipurpose applications. This study aims at synthesis and LCST-type thermoresponsive behaviors of multisensitive linear and cyclic graft copolymers with polyacrylamide backbone and hydrophilic PEG grafts. The cloud point could be tuned by many factors, and the effect of cyclization was confirmed by the elevated cloud point in H₂O up to 12.8 °C under same conditions. The PEG-connecting Y junctions with dual amide, thioether, and tertiary amine groups allowed thermo-, solvent-, pH-, and CO₂-switchable inter/intramolecular hydrogen bonding interactions and hence resulted in unusual solvent (H₂O or D₂O) and pH (about 6.8–8.5) dependent phase transition and irreversible CO₂-responsive behavior. Meanwhile, the solution blending could lead to one or two phase transition(s) dependent on types and compositions of the blends. The meticulous introduction of multifunctional Y junctions into graft copolymers offers a versatile route to adjust multitunable thermoresponsive properties

MiRNA-BD: an evidence-based bioinformatics model and software tool for microRNA biomarker discovery

<p>MicroRNAs (miRNAs) are small non-coding RNAs with the potential as biomarkers for disease diagnosis, prognosis and therapy. In the era of big data and biomedical informatics, computer-aided biomarker discovery has become the current frontier. However, most of the computational models are highly dependent on specific prior knowledge and training-testing procedures, very few are mechanism-guided or evidence-based. To the best of our knowledge, untill now no general rules have been uncovered and applied to miRNA biomarker screening. In this study, we manually collected literature-reported cancer miRNA biomarkers and analyzed their regulatory patterns, including the regulatory modes, biological functions and evolutionary characteristics of their targets in the human miRNA-mRNA network. Two evidences were statistically detected and used to distinguish biomarker miRNAs from others. Based on these observations, we developed a novel bioinformatics model and software tool for miRNA biomarker discovery (<a href="http://sysbio.suda.edu.cn/MiRNA-BD/" target="_blank">http://sysbio.suda.edu.cn/MiRNA-BD/</a>). In contrast to routine methods that focus on miRNA synergic functions, our method searches for vulnerable sites in the miRNA-mRNA network and considers the independent regulatory power of miRNAs, i.e., single-line regulations between miRNAs and mRNAs. The performance comparison demonstrates the generality and precision of our model, which identifies miRNA biomarkers for cancers as well as other complex diseases without training or specific prior knowledge.</p

CO₂‑Triggered Pickering Emulsion Based on Silica Nanoparticles and Tertiary Amine with Long Hydrophobic Tails

We describe a strategy of fabricating CO₂-triggered oil-in-water Pickering emulsion based on silica nanoparticles functionalized in situ by a trace amount of conventional CO₂-switchable surfactant, <i>N</i>-(3-(dimethyl­amino)­propyl)­alkyl amide (C_<i>n</i>PMA). By alternately bubbling CO₂ and N₂ at a moderate conditions (30 °C, 80 mL min^–1), silica nanoparticles reversibly switch between amphipathic and hydrophilic as a result of the adsorption of ammonium (CO₂) and the desorption of tertiary amine (N₂). The emulsion can then be smart switched “on (stable)” and “off (unstable)”, along with homogenization, without needing cooling and heating. The switching of the current tertiary-based system is simple, moderate, and environmentally friendly, without contamination and the restriction of rigorous conditions. The surfactant concentration window of the Pickering emulsion is closely related to the length of hydrophobic tail, and the upper limit is no more than 0.20 cmc of that of the corresponding ammonium surfactant. Such a strategy is also suitable for commercial alkyl tertiary amines, without needing complicated organic synthesis

sj-docx-1-taj-10.1177_20406223221122478 – Supplemental material for Association of NAFLD with cardiovascular disease and all-cause mortality: a large-scale prospective cohort study based on UK Biobank

Supplemental material, sj-docx-1-taj-10.1177_20406223221122478 for Association of NAFLD with cardiovascular disease and all-cause mortality: a large-scale prospective cohort study based on UK Biobank by Wen Ma, Wentao Wu, Weixing Wen, Fengshuo Xu, Didi Han, Jun Lyu and Yuli Huang in Therapeutic Advances in Chronic Disease</p

Effect of TET on LPS-stimulated MAPK activity in BV2 cells.

<p>BV2 cells were treated with TET at working concentrations for 2 h.Then, LPS was added to each plate and incubated at 37°C for an additional 24 h. Thereafter, the cells were lysed for protein extraction. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102522#pone-0102522-g007" target="_blank">Fig. 7a</a>: Western blot assay was performed to evaluate the expression of total and phosphorylated forms of ERK1/2, JNK, and p38. <i>β</i>-actin was applied as the internal control. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102522#pone-0102522-g007" target="_blank">Fig. 7b</a>: The ratio of densitometry values of total and phosphorylated forms of the protein was normalized to each respective control group. <i>β</i>-actin was applied as the internal control. Results were the mean ± S.D. from three independent experiments performed in triplicate. * <i>P</i><0.05 compared with the LPS group.</p

Effect of TET on LPS-stimulated NF-κB activity in BV2 cells.

<p>BV2 cells were treated with TET at working concentrations for 2 h. Then, LPS was added to each plate and incubated at 37°C for an additional 24 h. Then, the cells were lysed for protein extraction. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102522#pone-0102522-g006" target="_blank">Fig. 6a</a>: p-p65, p65, p-IKK, IKK, and <i>β</i>-actin expression were measured by Western blotting analysis. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102522#pone-0102522-g006" target="_blank">Fig. 6b–6c</a>: The ratio of densitometry values of total and phosphorylated protein was normalized to each respective control group. <i>β</i>-actin was applied as the internal control. Results were the mean ± S.D. from three independent experiments performed in triplicate. * <i>P</i><0.05 compared with the LPS group.</p

The expression of IL1β and TNFα was attenuated by TET in BV2 cells.

<p>BV2 cells were treated with TET at working concentrations for 2 h. Then, LPS was added to each plate and incubated at 37°C for an additional 24 h. Then, the supernatant was collected and stored at −80°C for further ELISA assay. The cells were lysed for RNA extraction. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102522#pone-0102522-g005" target="_blank">Fig. 5a–5b</a>: The mRNA expression of IL1β and TNFα was determined by real-time RT-PCR. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102522#pone-0102522-g005" target="_blank">Fig. 5c–5d</a>: The production of IL1β and TNFα was measured by enzyme-linked immunosorbent assay (ELISA). Results were the mean ± S.D. from three independent experiments performed in triplicate. * <i>P</i><0.05 compared with the LPS group.</p

Primers Used for Quantitative RT-PCR.

<p>Primers Used for Quantitative RT-PCR.</p

Effect of TET on the cell viability of BV2 cells.

<p>BV2 cells were treated with TET at various concentrations for 2 h. Then, LPS was added to each well and incubated at 37°C for an additional 24 h. Cell viability was measured by CCK-8 assay. Results were expressed as a percentage of the control cultures and the mean ±S.D. from three independent experiments performed in triplicate. * <i>P</i><0.05 compared with the LPS (−) TET (−) group.</p

The percentage of apoptotic BV2 cells induced by TET.

<p>BV2 cells were treated with TET at various concentrations for 2 h; then, LPS was added to each plate and incubated at 37°C for an additional 24 h. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102522#pone-0102522-g002" target="_blank">Fig. 2a–2f</a>: Cell apoptosis was monitored by FACS using an Annexin V-FITC Apoptosis Kit. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102522#pone-0102522-g002" target="_blank">Fig. 2e</a>: Results were expressed as a percentage of apoptosis cells and were the mean ± S.D. from three independent experiments performed in triplicate. * <i>P</i><0.05 compared with the LPS(−)TET(−) group.</p