The long noncoding RNA NEAT1 contributes to hepatocellular carcinoma development by sponging miR-485 and enhancing the expression of the STAT3.

Accumulating evidence has supported the significance of lncRNAs in tumorigenesis. Recently, some studies indicate the oncogenic role of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in hepatocellular carcinoma (HCC). In our present study, we focused on the biological mechanisms through which NEAT1 can regulate HCC development. We found that NEAT1 was greatly upregulated in human HCC cell lines including Huh7, Hep3B, HepG2, Bel-7404, and SK-Hep1 cells compared to the normal human liver cell line LO2. In addition, we observed that miR-485 was significantly downregulated in HCC cells. It was implied that miR-485 was increased by sh-NEAT1 and miR-485 can modulate NEAT1 expression negatively. Meanwhile, NEAT1inhibiton can repress HCC growth, migration, and invasion capacity in HepG2 and Hep3B cells. Through performing bioinformatic analysis, dual-luciferase reporter test, RNA-binding protein immunoprecipitation, and RNA pull-down assay, miR-485 was confirmed as a interacting target of NEAT1. Additionally, STAT3 was recognized as a direct target of miR-485 and miR-485 mimics can inhibit STAT3 expression. It was demonstrated that NEAT1 can increase STAT3 levels while miR-485 mimics can repress STAT3. Moreover, we found that sh-STAT3 was able to restrain HCC cell migration and invasion process. NEAT1 can act as a competing endogenous lncRNA (ceRNA) to regulated STAT3 by sponging miR-485 in HCC. Taken these together, NEAT1 can be used as an important biomarker in HCC diagnosis and treatment.

A Fissionable Artificial Eukaryote-like Cell Model.

The use of artificial cells has attracted considerable attention in various fields from biotechnology to medicine. Here, we develop a cell-sized vesicle-in-vesicle (VIV) structure containing a separate inner vesicle (IV) that can be loaded with DNA. We use polymerase chain reaction (PCR) to successfully amplify the amount of DNA confined to the IV. Subsequent osmotic stress-induced fission of a mother VIV into two daughter VIVs successfully divides the IV content while keeping it confined to the IV of the daughter VIVs. The fission rate was estimated to be ∼20% quantified by fluorescence microscope. Our VIV structure represents a step forward toward construction of an advanced, fissionable cell model.

A pH-responsive asymmetric lipid vesicle as drug carrier.

In order to increase the loading efficiency of drug carriers, here we demonstrated a microfluidic method to fabricate an asymmetric vesicle, which contains trichloro(1H,1H,2H,2H-perfluoroocty-l)silane (TPS) inner leaflet and lipid outer leaflet. The asymmetric vesicle was characterised by fluorescence microscopy and Fourier transform infra-red spectrum. In vitro cytotoxicity of the vesicles carrying 5-fluorouacil (5-FU) has also been studied.

Polydopamine-coated liposomes as pH-sensitive anticancer drug carriers.

Stimuli-responsive drug carriers are considered to play important roles in chemotherapy. We fabricated pH-sensitive polydopamine-protected liposomes (liposome@PDA) drug delivery systems, which were characterised with microscope, scanning electron microscope (SEM), UV-vis spectrometer and Fourier transform infrared (FTIR) technieques. The typical chemotherapeutic agent, 5-fluorouracil (5-FU), was loaded into liposome@PDA capsules. The maximum release percentages of 5-FU are 3.2%, 29.5%, 52.7%, 76.7% in the solution with pH 7.42, 6.87, 4.11 and 3.16, respectively. The in vitro cell cytotoxity experiments were carried out using 5-FU-loaded capsules at pH 6.87 solution, which simulate the true pH around cancerous cells. At 1.5 µM concentration, the free 5-FU, 5-FU-loaded liposome capsules and 5-FU-loaded capsules showed the cell viability of 50.56%, 22.66% and 21.63%, respectively. It confirms that drug-loaded capsules performed better than free drug. The results demonstrate the great potential of liposome@PDA capsules as carriers in biomedical applications.

Ultrasensitive detection of chlortetracycline in animal-origin food using molecularly imprinted electrochemical sensor based on SnS2/ZnCo-MOF and AuNPs.

The chlortetracycline (CTC) residue in food poses a threat to human health. Therefore, developing sensitive, convenient and selective analytical methods for CTC detection is crucial. This study innovatively uses tin disulfide/bimetallic organic framework (SnS2/ZnCo-MOF) nanocomposites in conjunction with gold nanoparticles (AuNPs) to co-modify a glassy carbon electrode (GCE). Further, a molecularly imprinted polymer (MIP)-based electrochemical sensing platform Au-MIP/SnS2/ZnCo-MOF/Au/GCE (AZG) was fabricated for selective CTC detection. SnS2/ZnCo-MOF enhanced the stability and surface area of the AZG sensor. The presence of AuNPs facilitated electron transport between the probe and the electrode across the insulating MIP layer. The fixation of AuNPs and MIP via electropolymerization enhanced the selective recognition of this sensor and amplified its output signal. The AZG sensor demonstrated a wide linear detection range (0.1-100 µM), low detection limit (0.072 nM), and high sensitivity (0.830 µA µM-1). It has been used for detecting CTC in animal-origin food with good recovery (96.08%-104.60%).

Towards a biomimetic cellular structure and physical morphology with liposome-encapsulated agarose sol systems.

The cytoplasm, serving as the primary hub of cellular metabolism, stands as a pivotal cornerstone for the harmonious progression of life. The ideal artificial cell should not only have a biomembrane structure system similar to that of a cell and the function of carrying genetic information, but also should have an intracellular environment. In this pursuit, we employed a method involving the incorporation of glycerol into agarose, resulting in the formation of agarose-glycerol mixed sol (AGs). This dynamic sol exhibited fluidic properties at ambient temperature, closely mimicking the viscosity of authentic cytoplasm. Harnessing the electroformation technique, AGs was encapsulated within liposomes, enabling the efficient creation of artificial cells that closely resembled native cellular dimensions through meticulous parameter adjustments of the alternating current (AC) field. Subsequently, artificial cells harboring AGs were subjected to diverse electrolyte and non-electrolyte solutions, enabling a comprehensive exploration of their deformation phenomena, encompassing both inward and outward budding. This study represents a significant stride forward in addressing one of the most fundamental challenges in the construction of artificial cytoplasm. It is our fervent aspiration that this work shall offer invaluable insights and guidance for future endeavors in the realm of artificial cell construction.

Relationship between diffuse fibrosis assessed by CMR and depressed myocardial strain in different stages of heart failure.

OBJECTIVES: To investigate the extent of the left ventricular (LV) diffuse myocardial fibrosis and the association with the degree of impaired myocardial strain in different stages of heart failure. BACKGROUND: The increased diffuse myocardial fibrosis impairs the LV systolic and diastolic function. Previous studies found that the global longitudinal strain (GLS) impacted survival in patients with heart failure with preserved ejection fraction (HFpEF). However, limited data are available regarding the association between the degree of diffuse myocardial fibrosis and the severity of impaired myocardial strain in HFpEF. METHODS: Sixty-six consecutive participants with heart failure (HF), and 15 healthy controls underwent cardiac magnetic resonance (CMR) examination. T1 mapping to calculate extracellular volume fractions (ECV) were used to assess diffuse myocardial fibrosis. ECV and myocardial strains were compared among the 3 groups. Associations between these two factors were also explored. RESULTS: The patients with HFpEF showed increased myocardial ECV fractions (32.9 % ± 3.7 % vs. 29.2 % ± 2.9 %, p < 0.001) compared with the control group. The patients with HFm + rEF also had increased myocardial ECV fractions (36.8 % ± 5.4 % vs. 32.9 % ± 3.7 %, p < 0.001) compared with HFpEF. The myocardial ECV was significantly correlated with the GLS (r = 0.422, p = 0.020), global circumferential strain (GCS) (r = 0.491, p = 0.006), and global radial strain (GRS) (r = -0.533, p = 0.002) in the HFpEF groups, but no significant correlation was found in the HFm + rEF group (GLS: r = -0.002, p = 0.990; GCS: r = 0.153, p = 0.372; GRS: r = 0.070, p = 0.685) CONCLUSIONS: In patients with HF, only patients with HFpEF exhibited a significant correlation between increased diffuse myocardial fibrosis and impaired myocardial strain. Diffuse myocardial fibrosis plays a unique role in affecting myocardial strain in patients with HFpEF.

Digital Twin Assistant Active Design and Optimization of Steel Mega-Sub Controlled Structural System under Severe Earthquake Waves.

In order to support the best optimized design or strategy based on life-cycle data, the interrelation mechanisms between structure-form and structure-performance should be considered simultaneously and comprehensively besides of the material-property relationship. Here, the structure-property-performance relationship of a designed steel mega-sub controlled structural system (MSCSS) under the reported earthquake waves has been investigated through integrating the finite element simulations and the experimental validations. It can be found that the MSCSS configurations are capable of effectively optimizing the vibration responses with significantly decreased acceleration, which is also much better than the traditional megaframe structure with extra weight. Moreover, if the horizontal connections between the sub- and the megastructures are broken, the displacement of the megastructure will be smaller than that of the substructure. This is because only the vertical connections between the sub- and megastructures work, the larger displacements or the obvious response of the substructures should be caused by the extra weight of the damper on the top floor. It is worth mentioning that the formation of abrupt amplified ß of the top floors should be attributed to the sheath effect. Furthermore, the displacement of the substructure is one kind of energy dissipation. Its larger displacement will result in a greater amount of energy dissipation and better performance of the designed configuration. This work supports a digital twin assistant active design and optimization strategy to further improve the control effectiveness of the system and to enhance the mechanical performance of the optimized configuration of MSCSS.

Liposomes encapsulating artificial cytosol as drug delivery system.

The fabrication of cell models containing artificial cytosol is challenging. Herein we constructed an artificial cytosol contained cell model by electroformation method. Agarose was selected as the main component of the artificial cytosol, and sucrose was added into the agarose to regulate the sol viscosity and the phase transition temperature. The viscosity of the sol with the mass ratio (agarose-sucrose) 1:9 was closest to the natural cytosol. DSPC/20 mol% cholesterol was used to form large unilamellar vesicles (LUVs) as cell model compartment. The rhodamine release experiment confirmed that the unique release profile of agarose-sucrose@LUVs is suitable as a drug carrier. Doxorubicin is loaded in the agarose-sucrose@LUVs, and their half maximum inhibition concentration on HeLa cells is 0.016 µmol L-1, which means 28.7 times increase in inhibition efficiency over free doxorubicin.

Relations among sensitivity, specificity and predictive values of medical tests based on biomarkers.

Diagnostic tests are usually based on some quantitative biomarkers. Two key parameters used to characterise the quality of a test are test sensitivity and specificity. Predictive values of the disease status based on test results are also of interest in medical research and public health management. In this paper, we study the relations among sensitivity, specificity and predictive values of the test. The core concept is risk function, which is assumed to be an increasing function of the biomarker. Our results show that test sensitivity and specificity change in opposite directions. The positive predictive value and the sensitivity also change in opposite directions. Likewise, the negative predictive value and the specificity change in opposite directions.

Multiscale Analysis of Mechanical Properties of 3D Orthogonal Woven Composites with Randomly Distributed Voids.

Voids are common defects in 3D woven composites because of the complicated manufacturing processes of the composites. In this study, a micro-meso multiscale analysis was conducted to evaluate the influence of voids on the mechanical properties of three-dimensional orthogonal woven composites. Statistical analysis was implemented to calculate the outputs of models under the different scales. A method is proposed to generate the reasonable mechanical properties of the microscale models considering randomly distributed voids and fiber filaments. The distributions of the generated properties agree well with the calculated results. These properties were utilized as inputs for the mesoscale models, in which void defects were also considered. The effects of these defects were calculated and investigated. The results indicate that tensile and shear strengths were more sensitive to the microscale voids, while the compressive strength was more influenced by mesoscale voids. The results of this study can provide a design basis for evaluating the quality of 3D woven composites with void defects.

A Reliable Fracture Angle Determination Algorithm for Extended Puck's 3D Inter-Fiber Failure Criterion for Unidirectional Composites.

Determination of the fracture angle and maximum exposure value of extended Puck's 3D inter-fiber failure (IFF) criterion is of great importance for predicting the failure mechanism of unidirectional fiber-reinforced composites. In this paper, a reliable semi-analytical algorithm (RSAA) is presented for searching fracture angle and corresponding exposure value for the extended Puck's failure criterion. One hundred million cases are tested for verifying the accuracy of the present and other algorithms on Python using the strength-value-stress-state combinations more universal than those in previous literatures. The reliability of previous algorithms is discussed and counterexamples are provided for illustration. The statistical results show RSAA is adequate for implementation in extended Puck's criterion and much more reliable than previous algorithms. RSAA can correctly predict the results with a probability of over 99.999%.

Deformation of giant unilamellar vesicles under osmotic stress.

Biological membrane plays an important role in maintaining an osmotic equilibrium between the cytoplasm and the extracellular solution of cells. Here, the giant unilamellar vesicles (GUVs) as cell models were used to investigate the effect of osmotic stress on phospholipid membranes. The deformation of GUVs, including inward budding and outward budding, was systematically investigated by the osmotic press from glucose, sucrose, LiCl, and KCl solutions. The permeability (P) of DMPC, DMPC/10 mol% Chol GUVs, DMPC/25 mol% Chol GUVs, and DMPC/40 mol% Chol GUVs in glucose, sucrose, LiCl, and KCl solutions were all obtained. The P value decreases with the addition of more cholesterol in the bilayer. The monovalent cations caused higher permeability of lipid bilayer membranes due to their combination with phospholipids. The molar flux of water (J) value was found to be the key factor for determining the deformation state from mainly inward budding to mainly outward budding. The findings in this paper may help us to understand cell transformation triggered with osmotic stress.

Codelivery of doxorubicin and sodium tanshinone IIA sulfonate using multicompartmentalized vesosomes to enhance synergism and prevent doxorubicin-induced cardiomyocyte apoptosis.

Doxorubicin, one of the most effective antitumor drugs, causes serious adverse cardiac effects. As a derivative of tanshinone IIA, sodium tanshinone IIA sulfonate was exploited for curing cardiovascular disorders. The synergistic effect of the above drugs as a combination was investigated for treating cancer cells and attenuating myocardial apoptosis. A multicompartmentalized vesosome (MCV) was produced to co-deliver the drug combination. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and western blotting analysis demonstrated that the MCV can enhance the synergistic effect of the drug combination and promote the protection of STS in Dox-induced cardiomyocyte apoptosis.

Thylakoid Containing Artificial Cells for the Inhibition Investigation of Light-Driven Electron Transfer during Photosynthesis.

The fabrication of artificial cells containing nature components is challenging. Herein we construct a thylakoid containing artificial cell (TA-cell) by forming multicompartmental structure inside giant unilamellar vesicles (GUVs) using osmotic stress. The thylakoids are selectively loaded inside each compartment in GUVs to mimic "chloroplast". The TA-cells are able to carry out photosynthesis upon light on. The TA-cells keep their 50% functionality of electron transfer for 12 days, which is twice of those of free thylakoids. Using TA-cells the inhibition of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and heavy metal ions (Hg2+, Cu2+, Cd2+, Pb2+ and Zn2+) on the electron transfer process in TA-cells is systematically investigated. Their half maximal inhibitory concentration (IC50) values are 36.23 ± 1.87, 0.02 ± 0.01, 0.42 ± 0.08, 0.82 ± 0.12, 1.97 ± 0.21, and 4.08 ± 0.18 µM, respectively. Hg2+ is the most toxic ion for the photosynthesis process among these five heavy metal ions. This biomimetic system can be expanded to study other processes during the photosynthesis. The TA-cells pave a way to fabricate more complicated nature component containing artificial cells.

Hydrogen Sulfide Demonstrates Promising Antitumor Efficacy in Gastric Carcinoma by Targeting MGAT5.

Mannosyl (alpha-1,6-)-Glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase (MGAT5) is exclusively expressed in gastric carcinoma, and plays an essential role in cancer progression, but no targeted drug is available so far. The potential anti-cancer effect of Hydrogen Sulfide (H2S), has not been widely recognized. It intrigued broad interest to explore the clinical benefits of cancer therapy, with the current understanding of molecular mechanisms of H2S which remains very limited. In this study, we identify that H2S is an effective inhibitor of MGAT5, leading to reduce the expression of exclusively abnormal glycoprotein processes in gastric carcinoma. H2S specifically dissociation of karyopherin subunit alpha-2 (KPNA2) with Jun proto-oncogene (c-Jun) interaction, and blocking c-Jun nuclear translocation, and downregulation of MGAT5 expression at the level of gene and protein. Consequently, H2S impairs growth and metastasis in gastric carcinoma by targeting inhibits MGAT5 activity. In an animal tumor model study, H2S is well tolerated, inhibits gastric carcinoma growth and metastasis. Our preclinical work therefore supports that H2S acts as a novel inhibitor of MGAT5 that block tumorigenesis in gastric carcinoma. SIGNIFICANCE: This study shows that H2S can effective targeting inhibits MGAT5 activity, and demonstrates promising antitumor efficacy. These findings gain mechanistic insights into the anti-cancer capacity of H2S and may provide useful information for the clinical explorations of H2S in cancer treatment.

Hierarchical drug release of pH-sensitive liposomes encapsulating aqueous two phase system.

As promising drug delivery vehicles, previous investigations of liposomes as carriers are primarily focused on insertion and modification of lipid membrane interfaces. The utility of the inner core seems to be overlooked. Herein, we developed pH-sensitive liposomes (PSLs) containing an aqueous two phase system (ATPS), and intriguingly discovered their hierarchical release under acidic stimuli. ATPS containing two polymers (poly(ethylene glycol) (PEG) and dextran) is homogeneous above phase transition temperature when producing ATPS-liposomes, and separated into PEG-rich phase and dextran-rich phase after cooling down to room temperature. The overall release time of ATPS-liposomes is divided into two stages and prolonged compared to simple aqueous liposomes. The unique release profile is due to the disproportional distribution of drugs in two phases. Doxorubicin (DOX) is loaded in the ATPS-liposomes, and their half maximum inhibition concentration on HeLa cells is 0.018 µmol L-1, which means 27.5 fold increase in inhibition efficiency over free DOX.

Sample Size Calculations for Comparing Groups with Binary Outcomes.

Sample size is a critical parameter for clinical studies. However, to many biomedical and psychosocial investigators, power and sample size analysis seems like a magic trick of statisticians. In this paper, we continue to discuss power and sample size calculations by focusing on binary outcomes. We again emphasize the importance of close interactions between investigators and biostatisticians in setting up hypotheses and carrying out power analyses.

Oxidation of elemental mercury by modified spent TiO2-based SCR-DeNOx catalysts in simulated coal-fired flue gas.

In order to reduce the costs, the recycle of spent TiO2-based SCR-DeNOx catalysts were employed as a potential catalytic support material for elemental mercury (Hg(0)) oxidation in simulated coal-fired flue gas. The catalytic mechanism for simultaneous removal of Hg(0) and NO was also investigated. The catalysts were characterized by Brunauer-Emmett-Teller (BET), scanning electron microscope (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) method. Results indicated that spent TiO2-based SCR-DeNOx catalyst supported Ce-Mn mixed oxides catalyst (CeMn/SCR1) was highly active for Hg(0) oxidation at low temperatures. The Ce1.00Mn/SCR1 performed the best catalytic activities, and approximately 92.80% mercury oxidation efficiency was obtained at 150 °C. The inhibition effect of NH3 on Hg(0) oxidation was confirmed in that NH3 consumed the surface oxygen. Moreover, H2O inhibited Hg(0) oxidation while SO2 had a promotional effect with the aid of O2. The XPS results illustrated that the surface oxygen was responsible for Hg(0) oxidation and NO conversion. Besides, the Hg(0) oxidation and NO conversion were thought to be aided by synergistic effect between the manganese and cerium oxides.