Click and Fluoresce: A Bioorthogonally Activated Smart Probe for Wash-Free Fluorescent Labeling of Biomolecules

Bioorthogonally activated smart probes greatly facilitate the selective labeling of biomolecules in living system. Herein, we described a novel type of smart probes with tunable reaction rates, high fluorescence turn-on ratio, and easy access. The practicality of such probes was demonstrated by selective labeling of lipid and hCAII in Hela cells

Design, Synthesis, and Antitumor Evaluation of 4‑Amino-(1<i>H</i>)‑pyrazole Derivatives as JAKs Inhibitors

Abnormalities in the JAK/STAT signaling pathway lead to many diseases such as immunodeficiency, inflammation, and cancer. Herein, we designed and synthesized a series of 4-amino-(1<i>H</i>)-pyrazole derivatives as potent JAKs inhibitors for cancer treatment. Results from <i>in vitro</i> protein kinase inhibition experiments indicated that compounds <b>3a</b>–<b>f</b> and <b>11b</b> are potent JAKs inhibitors. For example, the IC₅₀ values of compound <b>3f</b> against JAK1, JAK2, and JAK3 were 3.4, 2.2, and 3.5 nM, respectively. In cell culture experiments, compound <b>3f</b> showed potent antiproliferative activity against various cell lines (PC-3, HEL, K562, MCF-7, and MOLT4) at low micromolar levels, while compound <b>11b</b> showed selective cytotoxicity at submicromolar levels against HEL (IC₅₀: 0.35 μM) and K562 (IC₅₀: 0.37 μM) cell lines. It is worth noting that both <b>3f</b> and <b>11b</b> showed more potent antiproliferative activities than the approved JAKs inhibitor Ruxolitinib

Effective wind and resuspended sediment at sites 1, 4 and 5 during the observation period.

<p>Effective wind and resuspended sediment at sites 1, 4 and 5 during the observation period.</p

Correlation between sediment resuspension rate and total nitrogen (TN) or total phosphorus (TP) resuspension rate at each site during the observation period.

<p>Correlation between sediment resuspension rate and total nitrogen (TN) or total phosphorus (TP) resuspension rate at each site during the observation period.</p

Chlorophyll <i>a</i> concentrations at each site in the water column of phytoplankton- and macrophyte-dominated zone during the observation period.

<p>Chlorophyll <i>a</i> concentrations at each site in the water column of phytoplankton- and macrophyte-dominated zone during the observation period.</p

Dynamic ratio and sediment resuspension rate (R) in different lakes.

<p>Peak suspended solid concentrations during resuspension were used for Saginaw Bay and Lake Okeechobee instead of sediment resuspension rate (R) data in this figure, as there was no detailed sediment resuspension rate data in the references [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127915#pone.0127915.ref052" target="_blank">52</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127915#pone.0127915.ref053" target="_blank">53</a>]. The trend line showing the relationship between R and dynamic ratio was calculated excluding Lake Markermeer.</p

Ratios of average wind speed, effective wind, sediment resuspension rate, total nitrogen (TN) and total phosphorus (TP) resuspension rate during the high productive season to the low productive season at sites 1 and 4.

<p>Ratios of average wind speed, effective wind, sediment resuspension rate, total nitrogen (TN) and total phosphorus (TP) resuspension rate during the high productive season to the low productive season at sites 1 and 4.</p

Nitrogen (N) and phosphorus (P) resuspension rate at each site during the observation period.

<p>Figures of sites 1, 2, 3 and 6 with gray shading have the same value for y-axis, and figures of sites 4 and 5 have smaller value for y-axis.</p

The distances from each site to the shorelines in four directions (km).

<p>The distances from each site to the shorelines in four directions (km).</p

Sediment properties at each site during the observation.

<p>Sediment properties at each site during the observation.</p