Thermodynamic Phase Diagram for the Yeast Cell–Cycle Network

<p>Native phase with global minimum G0/G1 state or steady state; non-native phase with states less overlapping with global minimum G0/G1 state or steady state; trapping phase with states trapped into the local minimum. The larger of δU/T and smaller of ΔU/T, or the larger <i>δ</i>U/ΔU, the more likely the global minimum G1 state is thermodynamically stable and robust.</p

Figure 4

<p>The Free Energy as a Function of Overlap Parameter Q Relative to the Global Minimum G1 Steady-State Fixed Point at Low Temperature (50,000), Intermediate Temperature (77,500), and High Temperature (100,000)</p

Cell Cycle Network Scheme

<p>aa, amino acids; ∼P, ATP; Pi, inorganic phosphate</p

The Global Structures and Properties of the Underlying Potential Landscape of the Yeast Cell–Cycle Network

<div><p>(A) The histogram or the distribution of the potential U.</p><p>(B) The potential landscape spectrum.</p><p>(C) The funnelled landscape of the yeast cell–cycle network.</p><p>(D) The averaged potential as a function of similarity parameter Q with respect to the global minimum G1 state (or global steady state) of potential U.</p><p>(E) The entropy as a function of similarity order parameter Q with respect to the global minimum G1 state (or global steady state) of the potential U.</p></div

Figure 3

<p>The Averaged Potential U as a Function of Similarity Parameter Q with Respect to the Global Minimum G1 State (or Global Steady State) of Potential U against Perturbations of Chemical Rate Coefficient Parameters with 10% Increase (Decrease), 20% Increase (Decrease)</p

In Situ-Grown 2D Perovskite Based on π‑Conjugated Aggregation-Induced Emission Organic Spacer Boosting the Efficiency and Stability of 2D–3D Heterostructured Perovskite Solar Cells

The two-dimensional–three-dimensional (2D–3D) heterostructured perovskite solar cells (PSCs) have drawn widespread interest, wherein the organic spacer plays a significant role in the photovoltaic performance. Herein, a novel π-conjugated organic spacer with the aggregation-induced emission (AIE) property, (Z)-2-([1,1′-biphenyl]-4-yl)-3-(5-(4-(3-aminopropoxy)phenyl)thiophen-2-yl)acrylonitrile (BPCSA-S), is designed and synthesized, which is successfully applied for the in situ construction of 2D–3D heterostructured PSCs via the two-step solution method. By virtue of the functional groups (i.e., cyano, thiophene, and amino) in BPCSA-S, the BPCSA-S organic spacer can trigger the in situ growth of 2D perovskites, which will serve as the template for the heteroepitaxial growth of 3D perovskites, thus obtaining a 2D–3D heterostructured film with high-quality and few defects. More pleasingly, benefiting from the AIE property and delocalized π-electrons in the π-conjugated BPCSA-S organic spacer, excellent photosensitization process and carrier transport can be achieved. Consequently, the resultant 2D–3D heterostructured PSCs yield a pleasing PCE of 22.07%, accompanied by mitigatory hysteresis, as well as enhanced stability. Our research shows a hopeful multifunctional organic spacer approach using the novel π-conjugated AIE organic spacer for high-performance PSCs

Room-Temperature and Solution-Processable Cu-Doped Nickel Oxide Nanoparticles for Efficient Hole-Transport Layers of Flexible Large-Area Perovskite Solar Cells

Flexible perovskite solar cells (PSCs) using plastic substrates have become one of the most attractive points in the field of thin-film solar cells. Low-temperature and solution-processable nanoparticles (NPs) enable the fabrication of semiconductor thin films in a simple and low-cost approach to function as charge-selective layers in flexible PSCs. Here, we synthesized phase-pure p-type Cu-doped NiO_<i>x</i> NPs with good electrical properties, which can be processed to smooth, pinhole-free, and efficient hole transport layers (HTLs) with large-area uniformity over a wide range of film thickness using a room-temperature solution-processing technique. Such a high-quality inorganic HTL allows for the fabrication of flexible PSCs with an active area >1 cm², which have a power conversion efficiency over 15.01% without hysteresis. Moreover, the Cu/NiO_<i>x</i> NP-based flexible devices also demonstrate excellent air stability and mechanical stability compared to their counterpart fabricated on the pristine NiO_<i>x</i> films. This work will contribute to the evolution of upscaling flexible PSCs with a simple fabrication process and high device performances

SIRT1 is a Direct Coactivator of Thyroid Hormone Receptor β1 with Gene-Specific Actions

<div><p>Sirtuin 1 (SIRT1) NAD⁺-dependent deacetylase regulates energy metabolism by modulating expression of genes involved in gluconeogenesis and other liver fasting responses. While many effects of SIRT1 on gene expression are mediated by deacetylation and activation of peroxisome proliferator activated receptor coactivator α (PGC-1α), SIRT1 also binds directly to DNA bound transcription factors, including nuclear receptors (NRs), to modulate their activity. Since thyroid hormone receptor β1 (TRβ1) regulates several SIRT1 target genes in liver and interacts with PGC-1α, we hypothesized that SIRT1 may influence TRβ1. Here, we confirm that SIRT1 cooperates with PGC-1α to enhance response to triiodothyronine, T₃. We also find, however, that SIRT1 stimulates TRβ1 activity in a manner that is independent of PGC-1α but requires SIRT1 deacetylase activity. SIRT1 interacts with TRβ1 <i>in vitro</i>, promotes TRβ1 deacetylation in the presence of T₃ and enhances ubiquitin-dependent TRβ1 turnover; a common response of NRs to activating ligands. More surprisingly, SIRT1 knockdown only strongly inhibits T₃ response of a subset of TRβ1 target genes, including glucose 6 phosphatase (G-6-Pc), and this is associated with blockade of TRβ1 binding to the G-6-Pc promoter. Drugs that target the SIRT1 pathway, resveratrol and nicotinamide, modulate T₃ response at dual TRβ1/SIRT1 target genes. We propose that SIRT1 is a gene-specific TRβ1 co-regulator and TRβ1/SIRT1 interactions could play important roles in regulation of liver metabolic response. Our results open possibilities for modulation of subsets of TR target genes with drugs that influence the SIRT1 pathway.</p></div

Application of Circulating Tumor DNA as a Non-Invasive Tool for Monitoring the Progression of Colorectal Cancer

<div><p>Background</p><p>Liquid biopsy has been proposed to be a promising noninvasive tool to obtain information on tumor progression. Through a clinical observation of a case series of 6 consecutive patients, we aim to determine the value of circulating tumor DNA (ctDNA) for monitoring the tumor burden during the treatment of colorectal cancer (CRC).</p><p>Materials and Methods</p><p>We used capture sequencing of 545 genes to identify somatic alternations in primary tumor tissues of the six CRC patients who underwent radical surgery and in 23 plasma samples collected at serial time points. We compared the mutation patterns and variant allele frequencies (VAFs) between the matched tissue and the plasma samples and evaluated the potential advantage of using ctDNA as a better tumor load indicator to detect disease relapse over carcinoembryonic antigen (CEA), cancer antigen (CA) 19–9 and imaging studies.</p><p>Results</p><p>We identified low-frequency mutations with a mean VAF of 0.88% (corresponding to a mean tumor burden of 0.20ng/mL) in the preoperative plasmas of four patients with locally advanced CRC and a subset of mutations shared by their primary tumors. The tumor loads appeared a sudden decrease upon surgery or other adjuvant treatments and then generally maintained at low levels (0.092ng/mL) until disease recurred. ctDNA increased by 13-fold when disease relapsed in one patient while the CEA and CA 19–9 levels remained normal. In this patient, all six somatic mutations identified in the preoperative plasma were detected in the recrudescent plasma again, with five mutations showing allele fraction increase.</p><p>Conclusions</p><p>We described a multi-time-point profile of ctDNA of CRC patients during the course of comprehensive treatment and observed a correlation of ctDNA level with the clinically evaluated tumor progression. This demonstrated a new strategy by analyzing the heterogeneous ctDNA to evaluate and monitor the tumor burden in the treatment and follow-up of CRC patients, with potentially better potency than conventional biomarkers.</p></div

Mutated allele fraction of common somatic variations in preoperative blood versus blood sampled when disease was relapsing of patient 4.

<p>VAF, variant allele frequency.</p