Simple Monomers for Precise Polymer Functionalization During Ring-Opening Metathesis Polymerization

Controlling the monomer sequence of synthetic polymers is a grand challenge in polymer science. Conventional sequence control has been achieved in dispersed polymers by exploiting the kinetic tendencies of monomers and their order of addition. While the sequence of blocks in multiblock copolymers can be readily tuned using sequential addition of monomers (SAM), control over the sequence distribution is eroded as the targeted block size approaches a single monomer unit (i.e., Xn ∼ 1) due to the stochastic nature of chain-growth reactions. Thus, unique monomers are needed to ensure precise single additions. Herein, we investigate common classes of cyclic olefin monomers for ring-opening metathesis polymerization (ROMP) to identify monomers for single unit addition during sequential monomer addition synthesis. Through careful analysis of polymerization kinetics, we find that easily synthesized oxanorbornene imide monomers are suitable for single-addition reactions. With the identified monomers, we demonstrate the synthesis of multiblock copolymers containing up to three precise functionalization sites and singly cross-linked four-armed star copolymers. We envision that expanded kinetic analyses of monomer reactivities in ROMP reactions will enable novel polymer synthesis capabilities such as the autonomous synthesis of sequence-defined polymers or one-shot multiblock copolymer syntheses

Image_7_A novel nomogram to predict the overall survival of early-stage hepatocellular carcinoma patients following ablation therapy.jpeg

IntroductionThis study aimed to assess factors affecting the prognosis of early-stage hepatocellular carcinoma (HCC) patients undergoing ablation therapy and create a nomogram for predicting their 3-, 5-, and 8-year overall survival (OS).MethodsThe research included 881 early-stage HCC patients treated at Beijing You’an Hospital, affiliated with Capital Medical University, from 2014 to 2022. A nomogram was developed using independent prognostic factors identified by Lasso and multivariate Cox regression analyses. Its predictive performance was evaluated with concordance index (C-index), receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).ResultsThe study identified age, tumor number, tumor size, gamma-glutamyl transpeptidase (GGT), international normalized ratio (INR), and prealbumin (Palb) as independent prognostic risk factors. The nomogram achieved C-indices of 0.683 (primary cohort) and 0.652 (validation cohort), with Area Under the Curve (AUC) values of 0.776, 0.779, and 0.822 (3-year, 5-year, and 8-year OS, primary cohort) and 0.658, 0.724, and 0.792 (validation cohort), indicating that the nomogram possessed strong discriminative ability. Calibration and DCA curves further confirmed the nomogram’s predictive accuracy and clinical utility. The nomogram can effectively stratify patients into low-, intermediate-, and high-risk groups, particularly identifying high-risk patients.ConclusionsThe established nomogram in our study can provide precise prognostic information for HCC patients following ablation treatment and enable physicians to accurately identify high-risk individuals and facilitate timely intervention.</p

Image_1_A novel nomogram to predict the overall survival of early-stage hepatocellular carcinoma patients following ablation therapy.jpeg

IntroductionThis study aimed to assess factors affecting the prognosis of early-stage hepatocellular carcinoma (HCC) patients undergoing ablation therapy and create a nomogram for predicting their 3-, 5-, and 8-year overall survival (OS).MethodsThe research included 881 early-stage HCC patients treated at Beijing You’an Hospital, affiliated with Capital Medical University, from 2014 to 2022. A nomogram was developed using independent prognostic factors identified by Lasso and multivariate Cox regression analyses. Its predictive performance was evaluated with concordance index (C-index), receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).ResultsThe study identified age, tumor number, tumor size, gamma-glutamyl transpeptidase (GGT), international normalized ratio (INR), and prealbumin (Palb) as independent prognostic risk factors. The nomogram achieved C-indices of 0.683 (primary cohort) and 0.652 (validation cohort), with Area Under the Curve (AUC) values of 0.776, 0.779, and 0.822 (3-year, 5-year, and 8-year OS, primary cohort) and 0.658, 0.724, and 0.792 (validation cohort), indicating that the nomogram possessed strong discriminative ability. Calibration and DCA curves further confirmed the nomogram’s predictive accuracy and clinical utility. The nomogram can effectively stratify patients into low-, intermediate-, and high-risk groups, particularly identifying high-risk patients.ConclusionsThe established nomogram in our study can provide precise prognostic information for HCC patients following ablation treatment and enable physicians to accurately identify high-risk individuals and facilitate timely intervention.</p

U0126 attenuates spontaneous nociceptive responses, the elevation of p-Cdk5^S159 and Cdk5 activity in SCDH induced by formalin administration.

<p>a. U0126 treatment significantly decreases the numbers of spontaneous flinches induced by formalin injection in the 2^nd phase (10–45 min), but not in the 1^st phase (0–10 min). Data were analyzed by two-way ANOVA with repeated measures followed by Bonferroni's multiple-comparison tests. b. U0126 mitigates formalin-induced p-Cdk5 increase in spinal cord in the Western blot analysis. c. Quantification of the Western blot shows that the increase of p-Cdk5^S159 by formalin is attenuated after U0126 treatment, **p<0.01. d. U0126 mitigates formalin-induced Cdk5 kinase activity in spinal cord detected by an in vitro phosphorylation assay. Histone H1 was used as a substrate. e. Quantification of Cdk5 activity (density of phosphorylated H1 band) in the SCDH, **p<0.01, ***p<0.001.</p

Intrathecal administration of U0126 attenuates CFA-induced heat hyperalgesia.

<p>a. PWLs to thermal stimuli significantly decreases after intraplantar injection of CFA; **p<0.01. b. Compared to the PWL of the control group treated with DMSO, PWL to thermal stimuli significantly increases following intrathecal injection of U0126 30 min before and once per day for 1 week after CFA injection. The symbols represent mean and vertical lines represented SD. Data were analyzed by two-way ANOVA with repeated measures followed by Bonferroni's multiple-comparison tests, *p<0.05, **p<0.01. c. 2 µg U0126 does not affect rat movement as detected by the inclined plane test before CFA administration. N = 6.</p

Roscovitine does not affect ERK1/2 activity in SCDH induced by CFA injection.

<p>a. Effects of roscovitine on the heat hyperalgesia compare to the DMSO treatment 2-way ANOVA with repeated measures followed by Bonferroni's multiple-comparison tests. *p<0.05, **p<0.01, n = 6. b. 100 µg roscovitine does not affect rat movement as detected by the inclined plane test before CFA administration, n = 6. c. Effects of roscovitine administration on ERK1/2 activity and p-Cdk5^S159 expression after CFA in the Western blot analysis. d and e. Quantification of the Western blot shows that roscovitine treatment does not affect ERK1/2 activity by CFA, **p<0.01, n = 3. f. Quantification of the Western blot shows that the increase of p-Cdk5^S159 by CFA is attenuated after roscovitine treatment, *p<0.05, **p<0.01, n = 3. g. Roscovitine treatment does not affect total-Cdk5 expression in spinal cord 1 d after CFA injection.</p

Levels of p-ERK and p-Cdk5^S159 increase in SCDH after formalin injection.

<p>a. Time courses of p-ERK1/2 (panel 1) and t-ERK1/2 expression (panel 3) from 5 min to 1 d after formalin injection in rats as compared to naïve condition (lane1) in the Western blot analysis. b. Quantification of ERK1 activity in the dorsal horn. Columns represent means ± SEM. Data were normalized to naïve control and ANOVA followed by Dunnett's Multiple Comparison Test. *P<0.05, **P<0.01, as compared with naive rats. c. Quantification of ERK2 activity in the dorsal horn. d. Time courses of p-Cdk5^S159 (panel 1) and t-Cdk5 (panel 3) expression from 5 min to 1 d after formalin injection in rats as compared to naïve condition (lane1) in the Western blot analysis. e. Quantification of levels in p-Cdk5^S159 in the dorsal horn.</p

U0126 attenuates p-Cdk5^S159 increase and Cdk5 activity in SCDH induced by CFA administration.

<p>a. U0126 mitigates CFA-induced p-ERK1/2 and p-Cdk5 increases in spinal cord in the Western blot analysis. b and c. Quantification of the Western blot shows that ERK1/2 activity by CFA is attenuated after U0126 treatment, *p<0.05, **p<0.01. d. Quantification of the Western blot shows that the increase of p-Cdk5^S159 by CFA is attenuated after U0126 treatment, **p<0.01, ***p<0.001. e. U0126 treatment does not affect total-ERK1/2 and total-Cdk5 expression in spinal cord 1 d after CFA injection. f. U0126 mitigates CFA-induced Cdk5 kinase activity in spinal cord detected by an in vitro phosphorylation assay. Histone H1 was used as a substrate. g. Quantification of Cdk5 activity (density of phosphorylated H1 band) in the SCDH. Columns represent means ± SEM for three separate experiments. h. Double-immunofluorescence staining for p-ERK (red), p-Cdk5 (green), Hoechst [a cell nuclear marker (blue)] in ipsilateral spinal enlargement at 1 day after CFA injection. P-Cdk5^S159 colocalizes with p-ERK (white arrow head).</p

Image_3_A novel nomogram to predict the overall survival of early-stage hepatocellular carcinoma patients following ablation therapy.jpeg

IntroductionThis study aimed to assess factors affecting the prognosis of early-stage hepatocellular carcinoma (HCC) patients undergoing ablation therapy and create a nomogram for predicting their 3-, 5-, and 8-year overall survival (OS).MethodsThe research included 881 early-stage HCC patients treated at Beijing You’an Hospital, affiliated with Capital Medical University, from 2014 to 2022. A nomogram was developed using independent prognostic factors identified by Lasso and multivariate Cox regression analyses. Its predictive performance was evaluated with concordance index (C-index), receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).ResultsThe study identified age, tumor number, tumor size, gamma-glutamyl transpeptidase (GGT), international normalized ratio (INR), and prealbumin (Palb) as independent prognostic risk factors. The nomogram achieved C-indices of 0.683 (primary cohort) and 0.652 (validation cohort), with Area Under the Curve (AUC) values of 0.776, 0.779, and 0.822 (3-year, 5-year, and 8-year OS, primary cohort) and 0.658, 0.724, and 0.792 (validation cohort), indicating that the nomogram possessed strong discriminative ability. Calibration and DCA curves further confirmed the nomogram’s predictive accuracy and clinical utility. The nomogram can effectively stratify patients into low-, intermediate-, and high-risk groups, particularly identifying high-risk patients.ConclusionsThe established nomogram in our study can provide precise prognostic information for HCC patients following ablation treatment and enable physicians to accurately identify high-risk individuals and facilitate timely intervention.</p

Image_6_A novel nomogram to predict the overall survival of early-stage hepatocellular carcinoma patients following ablation therapy.jpeg

IntroductionThis study aimed to assess factors affecting the prognosis of early-stage hepatocellular carcinoma (HCC) patients undergoing ablation therapy and create a nomogram for predicting their 3-, 5-, and 8-year overall survival (OS).MethodsThe research included 881 early-stage HCC patients treated at Beijing You’an Hospital, affiliated with Capital Medical University, from 2014 to 2022. A nomogram was developed using independent prognostic factors identified by Lasso and multivariate Cox regression analyses. Its predictive performance was evaluated with concordance index (C-index), receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).ResultsThe study identified age, tumor number, tumor size, gamma-glutamyl transpeptidase (GGT), international normalized ratio (INR), and prealbumin (Palb) as independent prognostic risk factors. The nomogram achieved C-indices of 0.683 (primary cohort) and 0.652 (validation cohort), with Area Under the Curve (AUC) values of 0.776, 0.779, and 0.822 (3-year, 5-year, and 8-year OS, primary cohort) and 0.658, 0.724, and 0.792 (validation cohort), indicating that the nomogram possessed strong discriminative ability. Calibration and DCA curves further confirmed the nomogram’s predictive accuracy and clinical utility. The nomogram can effectively stratify patients into low-, intermediate-, and high-risk groups, particularly identifying high-risk patients.ConclusionsThe established nomogram in our study can provide precise prognostic information for HCC patients following ablation treatment and enable physicians to accurately identify high-risk individuals and facilitate timely intervention.</p