Rapid and annealing-free self-assembly of DNA building blocks for 3D hydrogel chaperoned by cationic comb-type copolymers

<p>The construction and self-assembly of DNA building blocks are the foundation of bottom-up development of three-dimensional DNA nanostructures or hydrogels. However, most self-assembly from DNA components is impeded by the mishybridized intermediates or the thermodynamic instability. To enable rapid production of complicated DNA objects with high yields no need for annealing process, herein different DNA building blocks (Y-shaped, L- and L′-shaped units) were assembled in presence of a cationic comb-type copolymer, poly (L-lysine)-<i>graft</i>-dextran (PLL-<i>g</i>-Dex), under physiological conditions. The results demonstrated that PLL-<i>g</i>-Dex not only significantly promoted the self-assembly of DNA blocks with high efficiency, but also stabilized the assembled multi-level structures especially for promoting the complicated 3D DNA hydrogel formation. This study develops a novel strategy for rapid and high-yield production of DNA hydrogel even derived from instable building blocks at relatively low DNA concentrations, which would endow DNA nanotechnology for more practical applications.</p> <p>This work illustrates a cationic comb-type copolymer to promote the self-assembly of different DNA building units especially of complicated 3D DNA hydrogel with highly efficiency and stability.</p

Prognostic Value of Tumor-Infiltrating FoxP3⁺ T Cells in Gastrointestinal Cancers: A Meta Analysis

<div><p>Purpose</p><p>Tumor-infiltrating FoxP3⁺ T cells have been reported in various human tumors, which impaired cell-mediated immunity and promoted disease progression. However, its prognostic value for survival in patients with different gastrointestinal cancers [hepatocellular carcinoma (HCC), colorectal cancer (CRC), gastric cancer (GC)] remains controversial.</p><p>Methods</p><p>Relevant literature was searched using PubMed, Embase, Cochrane, Ovid Medline and Chinese wanfang databases. A meta-analysis was conducted to estimate pooled survival and recurrence ratios. The odds ratio (OR) and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.</p><p>Results</p><p>For HCC and GC, the overall survival at 1, 3 and 5-year of high FoxP3⁺ T cells infiltration patients were lower than low FoxP3⁺ T cells infiltration patients (<i>P</i><0.05). The recurrences at 1, 3 and 5-year of high FoxP3⁺ T cells infiltration patients were higher than low FoxP3⁺ T cells infiltration patients (<i>P</i><0.001). But for CRC, the overall survival at 1, 3 and 5-year of high FoxP3⁺ T cells infiltration patients were higher than low FoxP3⁺ T cells infiltration patients (<i>P</i><0.001). There were no differences in 1, 3 and 5-year recurrences between high and low FoxP3⁺ T cells infiltration patients (<i>P</i>>0.05).</p><p>Conclusions</p><p>Our findings suggested that tumor-infiltrating FoxP3⁺ T cells were a factor for a poor prognosis for HCC and GC, but a good prognosis for CRC.</p></div

Forest plot of HR for recurrence of CRC patients.

<p>Random effect model of odds ratio for recurrence of follow-up 1 (A), 3 (B), 5-year (C) of CRC patients after surgery: high FoxP3⁺ T cells infiltration patients <i>vs</i> low FoxP3⁺ T cells infiltration patients.</p

Main characteristics of studies about CRC included in the meta-analysis.

<p>F, female; M, male; Quality score was assessed using the validated Jadad scale; high FoxP3⁺ T cells infiltration; Low, low FoxP3⁺ T cells infiltration.</p

Forest plot of HR for survival of CRC patients.

<p>Fixed effect model of odds ratio for survival of follow-up 1 (A), 3 (B), 5-year (C) of CRC patients after surgery: high FoxP3⁺ T cells infiltration patients <i>vs</i> low FoxP3⁺ T cells infiltration patients.</p

Forest plot of HR for survival of GC patients.

<p>Random effect model of odds ratio for survival of follow-up 1 (A), 3 (B), 5-year (C) of GC patients after surgery: high FoxP3⁺ T cells infiltration patients <i>vs</i> low FoxP3⁺ T cells infiltration patients.</p

Forest plot of Hazard ratio (HR) for survival of HCC patients.

<p>Fixed effect model of odds ratio for survival of follow-up 1(A), 3-year (B) and random effect model of odds ratio for survival of follow-up 5-year (C) of HCC patients after surgery: high FoxP3⁺ T cells infiltration patients <i>vs</i> low FoxP3⁺ T cells infiltration patients.</p

Forest plot of HR for recurrence of HCC patients.

<p>Fixed effect model of odds ratio for recurrence of follow-up 1(A), 5-year (C) and random effect model of odds ratio for recurrence of follow-up 3-year (B) of HCC patients after surgery: high FoxP3⁺ T cells infiltration patients <i>vs</i> low FoxP3⁺ T cells infiltration patients.</p

Systemic injection of Hepa1-6 cells in syngeneic <i>C57BL6</i> mice.

<p>Hepa1-6 cells (2x10⁶) suspended in PBS were injected into <i>C57BL6</i> mice intravenously. (a) Morphological examination of tumor nodules in different tissues. The results showed that tumor formation in lung, heart and ribs. (b) Histological assessment of liver tumor nodules in lung, liver and heart (scale bar = 50 μm). A’, B’ or C’ represents the corresponding magnified boxed area from A, B or C.</p

Intrasplenic and intrahepatic inoculation of Hepa1-6 cells in <i>C57BL6</i> mice.

<p>Hepa1-6 cells (2x10⁶) suspended in PBS were injected into <i>C57BL6</i> mice intrasplenicly or intrahepatically as described in Materials and Methods. (a) Morphological examination of tumor nodules in different tissues from orthotopic HCC mice generated by intrasplenic inoculation of Hepa1-6 cells. The results showed the tumor formation in liver and spleen. (b) Histological assessment of liver tumor nodules in spleen, liver and lung (scale bar = 100 μm). A’, B’ or C’ represents the corresponding magnified boxed area from A, B or C. (c) MRI analysis of the progression of liver tumors after intrahepatic inoculation of Hepa1-6 cells at different time-points. Arrows point to the tumor nodules. (d) Morphological examination of tumor nodules in liver from orthotopic HCC mice via intrahepatic injection of Hepa1-6 cells. The results showed both solitary and multinodular tumors formed in liver. (e) Histological assessment of liver tumor nodules in liver and lung (scale bar = 100 μm). A’, B’ or C’ represents the corresponding magnified boxed area from A, B or C.</p