miR-579-3p Controls Hepatocellular Carcinoma Formation by Regulating the Phosphoinositide 3-Kinase-Protein Kinase B Pathway in Chronically Inflamed Liver

Chronic liver inflammation causes continuous liver damage with progressive liver fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma (HCC). Whereas the 10-year incidence for HCC in patients with cirrhosis is approximately 20%, many of these patients remain tumor free for their entire lives. Clarifying the mechanisms that define the various outcomes of chronic liver inflammation is a key aspect in HCC research. In addition to a wide variety of contributing factors, microRNAs (miRNAs) have also been shown to be engaged in promoting liver cancer. Therefore, we wanted to characterize miRNAs that are involved in the development of HCC, and we designed a longitudinal study with formalin-fixed and paraffin-embedded liver biopsy samples from several pathology institutes from Switzerland. We examined the miRNA expression by nCounterNanostring technology in matched nontumoral liver tissue from patients developing HCC (n = 23) before and after HCC formation in the same patient. Patients with cirrhosis (n = 26) remaining tumor free within a similar time frame served as a control cohort. Comparison of the two cohorts revealed that liver tissue from patients developing HCC displayed a down-regulation of miR-579-3p as an early step in HCC development, which was further confirmed in a validation cohort. Correlation with messenger RNA expression profiles further revealed that miR-579-3p directly attenuated phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) expression and consequently protein kinase B (AKT) and phosphorylated AKT. In vitro experiments and the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology confirmed that miR-579-3p controlled cell proliferation and cell migration of liver cancer cell lines. Conclusion: Liver tissues from patients developing HCC revealed changes in miRNA expression. miR-579-3p was identified as a novel tumor suppressor regulating phosphoinositide 3-kinase-AKT signaling at the early stages of HCC development

Airborne chemical sensing with mobile robots

Airborne chemical sensing with mobile robots has been an active research areasince the beginning of the 1990s. This article presents a review of research work in this field,including gas distribution mapping, trail guidance, and the different subtasks of gas sourcelocalisation. Due to the difficulty of modelling gas distribution in a real world environmentwith currently available simulation techniques, we focus largely on experimental work and donot consider publications that are purely based on simulations

Pressurizing the van der Waals magnet FeOCl at low temperatures: Phase transitions and structural evolution

Magnetic order is frustrated on the orthorhombic lattice of van der Waals layered FeOCl. Antiferromagnetic (AFM) order is attained at ambient pressure upon cooling through $T_N$=81 K, due to an accompanying monoclinic lattice distortion lifting the magnetic frustration. Within the paramagnetic state at 293 K, an incommensurate structural modulation appears above a critical pressure of $p_c$≈15 GPa, while orthorhombic symmetry is retained. This modulation is related to an optimization of the packing of chlorine atoms within the van der Waals gap. Here, we report four new phases in the pressure-temperature (p,T) phase diagram of FeOCl below room temperature. High-pressure–low-temperature single-crystal x-ray diffraction (SXRD) up to 37.8 GPa reveals that, at 100 K, the AFM transition occurs at p=7.3±1.3 GPa. The pressure coefficient of $ΔT_N/Δp=2$.13 K/GPa explains that FeOCl remains paramagnetic up to the highest measured pressure of 33.3 GPa at 293 K. At 6 and 100 K, the structural modulation appears around $p_c$≈15 GPa within the AFM ordered phase with monoclinic symmetry. The monoclinic and triclinic lattice distortions increase with pressure up to $γ$=90.64(1)∘, much larger than the maximum value of 90.1∘, that can be reached upon cooling at ambient pressure. The structural evolution provides the geometrical basis for the increase with the pressure of direct 3d−3d exchange and superexchange interactions. It is proposed, that a strong monoclinic lattice distortion may be of importance for understanding the properties of single-layer FeOCl materials

Pressure-dependent distortions in quasi-two-dimensional magnetic CrOCl at low temperatures

The layered van der Waals compound CrOCl is frustrated for antiferromagnetic (AFM) order, because of its orthorhombic Pmmn symmetry that supports a triangular lattice of magnetic Cr3+ ions. At ambient pressure, CrOCl develops incommensurate AFM order below T$_c$=27.2K, and it becomes AFM ordered with a fourfold magnetic supercell below the Néel temperature T$_{N,1bar}$=13.5K. This AFM order is facilitated by an a-unique monoclinic lattice distortion. At room temperature, CrOCl remains orthorhombic up to at least 57 GPa. It develops a structural modulation that is the result of the optimization of the packing of Cl atoms within the van der Waals gap. Single-crystal x-ray diffraction (SXRD) at conditions of high pressure and low temperature (HPLT) uncover three novel HPLT phases of CrOCl. Instead of an a-unique monoclinic lattice, major distortions are found for the lattice parameter angles β and γ, resulting in a c-unique HPLT phase at 35 K, a triclinic HPLT phase at both 14 and 35 K, and a structurally modulated, triclinic phase at yet higher pressures. The structurally modulated phases appear at nearly the same critical pressures of 15.0<p$_c$<16.0GPa, and they are of a similar nature at 14, 35, and 293 K, despite the different lattice symmetries. The unmodulated triclinic phase is proposed to lead to more favorable distortions within the double layers CrO than is possible within the high-symmetry structures at equivalent (p,T) conditions. Incommensurate magnetic order or commensurate AFM order may appear with the c-unique HPLT phase at 35 K. This then implies a substantial pressure dependence of the magnetic transitions of ΔT$_c$/Δp=1.42 K/GPa or ΔT$_N$/Δp=4.1 K/GPa, respectively. The present finding of substantial lattice distortions involving the angle γ may have ramifications for monolayer structures of CrOCl

Single-crystal-to-single-crystal phase transitions of commensurately modulated sodium saccharinate 1.875-hydrate

This work reports reversible, single-crystal-to-single-crystal phase transitions of commensurately modulated sodium saccharinate 1.875-hydrate [Na(sac)(15/8)H$_2$O]. The phases were studied in the temperature range 298 to 20 K. They exhibit complex disordered states. An unusual reentrant disorder has been discovered upon cooling through a phase transition at 120 K. The disordered region involves three sodium cations, four water molecules and one saccharinate anion. At room temperature, the structure is an eightfold superstructure that can be described by the superspace group C$_2$/c(0σ$_2$0)s0 with q = (0, 3/4, 0). It demonstrates maximum disorder with the disordered chemical entities having slightly different but close to 0.50:0.50 disorder component ratios. Upon cooling, the crystal tends to an ordered state, smoothly reaching a unified disorder component ratio of around 0.90:0.10 for each of the entities. Between 130 and 120 K a phase transition occurs involving a sudden increase of the disorder towards the disorder component ratio 0.65:0.35. Meanwhile, the space group and general organization of the structure are retained. Between 60 and 40 K there is another phase transition leading to a twinned triclinic phase. After heating the crystal back to room temperature its structure is the same as before cooling, indicating a complete reversibility of the phase transitions