Serotonin promotes the proliferation of serum-deprived hepatocellular carcinoma cells via upregulation of FOXO3a

BACKGROUND: Peripheral serotonin is involved in tumorigenesis and induces a pro-proliferative effect in hepatocellular carcinoma (HCC) cells; however, the intracellular mechanisms by which serotonin exerts a mitogenic effect remain unclear. In this research, we examined whether FOXO3a, a transcription factor at the interface of crucial cellular processes, plays a role downstream of serotonin in HCC cells. RESULTS: The cell viability and expression of FOXO3a was assessed in three HCC cell lines (Huh7, HepG2 and Hep3B) during serum deprivation in the presence or absence of serotonin. Serum free media significantly inhibited HCC proliferation and led to reduced expression and nuclear accumulation of FOXO3a. Knockdown of FOXO3a enhanced the ability of serum deprivation to inhibit HCC cells proliferation. And overexpression of non-phosphorylated FOXO3a in HCC cells reversed serum-deprivation-induced growth inhibition. Serotonin reversed the serum-deprivation-induced inhibition of cell proliferation and upregulated FOXO3a in Huh7 cells; however, serotonin had no effect on the proliferation of serum-deprived HepG2 or Hep3B cells. In addition to proliferation, serotonin also induced phosphorylation of AKT and FOXO3a in serum-deprived Huh7 cells but not in HepG2 and Hep3B cells. However, the phosphorylation of FOXO3a induced by serotonin did not export FOXO3a from nucleus to cytoplasm in serum-deprived Huh7 cells. Consequently, we demonstrated that serotonin promoted the proliferation of Huh7 cells by increasing the expression of FOXO3a. We also provide preliminary evidence that different expression levels of the 5-HT2B receptor (5-HT(2B)R) may contribute to the distinct effects of serotonin in different serum-deprived HCC cells. CONCLUSIONS: This study demonstrates that FOXO3a functions as a growth factor in serum-deprived HCC cells and serotonin promotes the proliferation of serum-deprived HCC cells via upregulation of FOXO3a, in the presence of sufficient levels of the serotonin receptor 5-HT(2B)R. Drugs targeting the serotonin-5-HT(2B)R-FOXO3a pathway may provide a novel target for anticancer therapy

Direct Synthesis of Photosensitizable Bacterial Cellulose as Engineered Living Material for Skin Wound Repair

10.1002/adma.202109010ADVANCED MATERIALS341

The peritubular reinforcement effect of porous dentine microstructure.

In the current study, we evaluate the equivalent stiffness of peritubular reinforcement effect (PRE) of porous dentine optimized by the thickness of peritubular dentine (PTD). Few studies to date have evaluated or quantitated the effect of PRE on composite dentine. The miscrostructure of porous dentine is captured by scanning electron microscope images, and then finite element modeling is used to quantitate the deformation and stiffness of the porous dentine structure. By optimizing the radius of PTD and dentine tubule (DT), the proposed FE model is able to demonstrate the effect of peritubular reinforcement on porous dentine stiffness. It is concluded that the dentinal equivalent stiffness is reduced and degraded with the increase of the radius of DT (i.e., porosity) in the certain ratio value of Ep/Ei and certain radius of PTD, where Ep is the PTD modulus and Ei is the intertubular dentine modulus. So in order to ensure the whole dentinal equivalent stiffness is not loss, the porosity should get some value while the Ep/Ei is certain. Thus, PTD prevents the stress concentration around DTs and reduces the risk of DTs failure. Mechanically, the overall role of PTD appears to enhance the stiffness of the dentine composite structure. These results provide some new and significant insights into the biological evolution of the optimal design for the porous dentine microstructure. These findings on the biological microstructure design of dentine materials are applicable to other engineering structural designs aimed at increasing the overall structural strength

HOMO energy level regulation of novel conjugated copolymers for polymer solar cells

Three novel donor-acceptor (D-A) conjugated copolymers for polymer solar cells (PSC) are presented in this work. By Stille coupling polymerization, indacenodithiophene (IDT), as an electron-rich unit, was conjugated with an electron-deficient unit of isoindigo (IID), which led to a novel alternative copolymer IDT-IID (P1). Two electron-deficient units, 2,1,3-benzooxadiazole (BO) and diketopyrrolopyrrole (DPP), were respectively introduced in the polymerization of P1, and two novel IDT-based D-A1-D-A2 random copolymers IDT-IID-IDT-BO (P2) and IDT-IID-IDT-DPP (P3) were obtained. Thermal property tests indicated that these molecules possess relative stability and are suitable for solar cell applications. Optical and electrochemical measurements revealed that the HOMO energy levels of the three copolymers were -5.46 eV, -5.34 eV, and -5.23 eV respectively, while the LUMO levels were almost kept stable around -3.56 eV and the low band gap levels led to complete absorption in the visible region. The PSCs based on these copolymers were fabricated with the structure of ITO/PEDOT : PSS/polymer : PC71BM/Ca/Al, and the photovoltaic properties disclosed the relatively high values of open circuit voltage (V-oc) due to the low-lying HOMO energy levels of each copolymer. Hole mobility and atomic force microscopy (AFM) study were applied to improve the PSCs performance. Our work provides an efficient method to regulate the HOMO energy levels which will be beneficial for PSCs by synthesizing different conjugated copolymers

Research on the Cleaning Method of Unmanned Sweeper Based on Target Distribution Situation Analysis

Replacing traditional manual sweeping with unmanned sweepers in closed parks can not only greatly reduce labor costs, but also improve sweeping efficiency. Efficient path planning is the key technology for unmanned sweepers to complete the sweeping task. Existing unmanned sweepers are often based on fixed path sweeping or completely traversing the sweeping mode, this mode does not have the environmental adaptability, in the actual sweeping is often high energy cost, and sweeping is not complete. In this paper, an environment-adaptive sweeping path planning method is proposed to improve the sweeping intelligence and environmental adaptability of unmanned sweepers, reduce the energy consumption of sweeping and improve the efficiency of sweeping. Specifically, in this paper, we first use YOLOv5 to complete the accurate identification of individual garbage and obstacles in the road, and then work with LIDAR and Gaussian Mixture Model(GMM) to remove redundant targets. We also propose a Permutation Entropy(PE) value-based discrimination method to complete the target distribution posture analysis of each complex garbage pile. Finally, the traditional path planning problem is transformed into a combinatorial optimization problem of garbage areas, and a sweeping path accurate method based on Simulated Annealing(SA) algorithm is proposed. Through comprehensive theoretical analysis and simulation study, the optimality and effectiveness of the proposed method are proved by comparing A star and Coverage Path Planning(CPP) algorithms in a variety of experimental scenarios

A Novel Nanocomposite Particle of Hydroxyapatite and Silk Fibroin: Biomimetic Synthesis and Its Biocompatibility

A novel bone-like biomaterial of hydroxyapatite (HAP) and silk fibroin (SF) composite was developed by biomimetic synthesis. The composite was precipitated from drops of Ca(OH)2 suspension and H3PO4 solution with SF. With this method, the HAP nanocrystals were obtained by self-assembling on a SF surface whose c-axis was aligned with the long-axis direction of SF in microstructures; this shares the same misconstrues of collagen and HAP with that in the natural bone. The HAP/SF composite then demonstrated that it could promote osteoblast proliferation in vitro and new bone formation in vivo. The novel biomaterial is a promising material for bone replacement and regeneration

Polarization fatigue in antiferroelectric (Pb,La)(Zr,Ti)O 3 thin films: The role of the effective strength of driving waveform

International audienceIn this study, a critical parameter termed as " effective electric strength " is developed to depict polarization fatigue in antiferroelectric thin films. Specifically, the effect of pulse width, frequency, and magnitude of driving voltage (or field) on polarization fatigue of antiferroelectric (Pb,La) (Zr,Ti)O 3 (PLZT) thin films was investigated in detail. By transforming all the waveforms with different pulse-widths/voltages/frequencies into their effective electric strength, a strong correlation between the effective strength and the degree of polarization fatigue in the PLZT films is revealed. For instance, it was found that appreciable fatigue usually occurs when the effective strength is larger than or equal to the voltage of phase transition from antiferroelectric phase to ferroelectric phase. In addition, it is shown that the films are more prone to fatigue for a lower frequency of the same effective strength. Our findings could be well explained in the framework of the local phase decomposition arising from switching induced charge injection.

The relationship between <i>E</i>_<i>ff</i>, porosity and <i>E</i>_<i>p</i>/<i>E</i>_<i>i</i> when the <i>R</i>_PTD is kept the same.

<p>The relationship between <i>E</i>_<i>ff</i>, porosity and <i>E</i>_<i>p</i>/<i>E</i>_<i>i</i> when the <i>R</i>_PTD is kept the same.</p

The relationship between porosity, <i>m</i> and <i>E</i>_<i>p</i>/<i>E</i>_<i>i</i>.

<p>The relationship between porosity, <i>m</i> and <i>E</i>_<i>p</i>/<i>E</i>_<i>i</i>.</p