Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first. Full article

P-glycoprotein (P-gp) is an important determinant of multidrug resistance (MDR) because its overexpression is associated with increased efflux of various established chemotherapy drugs in many clinically resistant and refractory tumors. This leads to insufficient therapeutic targeting of tumor populations, representing a major drawback of cancer chemotherapy. Therefore, P-gp is a target for pharmacological inhibitors to overcome MDR. In the present study, we utilized machine learning strategies to establish a model for P-gp modulators to predict whether a given compound would behave as substrate or inhibitor of P-gp. Random forest feature selection algorithm-based leave-one-out random sampling was used. Testing the model with an external validation set revealed high performance scores. A P-gp modulator list of compounds from the ChEMBL database was used to test the performance, and predictions from both substrate and inhibitor classes were selected for the last step of validation with molecular docking. Predicted substrates revealed similar docking poses than that of doxorubicin, and predicted inhibitors revealed similar docking poses than that of the known P-gp inhibitor elacridar, implying the validity of the predictions. We conclude that the machine-learning approach introduced in this investigation may serve as a tool for the rapid detection of P-gp substrates and inhibitors in large chemical libraries. Full article

Non-small cell lung cancer (NSCLC) has been the leading cause of cancer-related death worldwide, over the last few decades. Survival remains extremely poor in the metastatic setting and, consequently, innovative therapeutic strategies are urgently needed. Inhibitor of Growth Gene 2 (ING2) is a core component of the mSin3A/Histone deacetylases complex (HDAC), which controls the chromatin acetylation status and modulates gene transcription. This gene has been characterized as a tumor suppressor gene and its status in cancer has been scarcely explored. In this review, we focused on ING2 and other mSin3A/HDAC member statuses in NSCLC. Taking advantage of existing public databases and known pharmacological properties of HDAC inhibitors, finally, we proposed a therapeutic model based on an ING2 biomarker-guided strategy. Full article

Distant organ liver damage after acute kidney injury (AKI) remains a serious clinical setting with high mortality. This undesirable outcome may be due to some hidden factors that can intensify the consequences of AKI. Exposure to bisphenol A (BPA), a universal chemical used in plastics industry, is currently unavoidable and can be harmful to the liver. This study explored whether BPA exposure could be a causative factor that increase severity of remote liver injury after AKI and examined the preventive benefit by N-acetylcysteine (NAC) in this complex condition. Male Wistar rats were given vehicle, BPA, or BPA + NAC for 5 weeks then underwent 45 min renal ischemia followed by 24 h reperfusion (RIR), a group of vehicle-sham-control was also included. RIR not only induced AKI but produced liver injury, triggered systemic oxidative stress as well as inflammation, which increasing severity upon exposure to BPA. Given NAC to BPA-exposed rats diminished the added-on effects of BPA on liver functional impairment, oxidative stress, inflammation, and apoptosis caused by AKI. NAC also mitigated the abnormalities in mitochondrial functions, dynamics, mitophagy, and ultrastructure of the liver by improving the mitochondrial homeostasis regulatory signaling AMPK-PGC-1α-SIRT3. The study demonstrates that NAC is an effective adjunct for preserving mitochondrial homeostasis and reducing remote effects of AKI in environments where BPA exposure is vulnerable. Full article

G-quadruplexes constitute a unique class of nucleic acid structures formed by G-rich oligonucleotides of DNA- or RNA-type. Depending on their chemical nature, loops length, and localization in the sequence or structure molecularity, G-quadruplexes are highly polymorphic structures showing various folding topologies. They may be formed in the human genome where they are believed to play a pivotal role in the regulation of multiple biological processes such as replication, transcription, and translation. Thus, natural G-quadruplex structures became prospective targets for disease treatment. The fast development of systematic evolution of ligands by exponential enrichment (SELEX) technologies provided a number of G-rich aptamers revealing the potential of G-quadruplex structures as a promising molecular tool targeted toward various biologically important ligands. Because of their high stability, increased cellular uptake, ease of chemical modification, minor production costs, and convenient storage, G-rich aptamers became interesting therapeutic and diagnostic alternatives to antibodies. In this review, we describe the recent advances in the development of G-quadruplex based aptamers by focusing on the therapeutic and diagnostic potential of this exceptional class of nucleic acid structures. Full article

Dry contact electrode-based EEG acquisition is one of the easiest ways to obtain neural information from the human brain, providing many advantages such as rapid installation, and enhanced wearability. However, high contact impedance due to insufficient electrical coupling at the electrode-scalp interface still remains a critical issue. In this paper, a two-wired active dry electrode system is proposed by combining finger-shaped spring-loaded probes and active buffer circuits. The shrinkable probes and bootstrap topology-based buffer circuitry provide reliable electrical coupling with an uneven and hairy scalp and effective input impedance conversion along with low input capacitance. Through analysis of the equivalent circuit model, the proposed electrode was carefully designed by employing off-the-shelf discrete components and a low-noise zero-drift amplifier. Several electrical evaluations such as noise spectral density measurements and input capacitance estimation were performed together with simple experiments for alpha rhythm detection. The experimental results showed that the proposed electrode is capable of clear detection for the alpha rhythm activation, with excellent electrical characteristics such as low-noise of 1.131 μV_RMS and 32.3% reduction of input capacitance. Full article

Antibody-drug conjugates (ADCs) are a class of biotherapeutic drugs designed as targeted therapies for the treatment of cancer. Among the challenges in generating an effective ADC is the choice of an effective conjugation site on the IgG. One common method to prepare site-specific ADCs is to engineer solvent-accessible cysteine residues into antibodies. Here, we used X-ray diffraction and hydrogen-deuterium exchange mass spectroscopy to analyze the structure and dynamics of such a construct where a cysteine has been inserted after Ser 239 (Fc-239i) in the antibody heavy chain sequence. The crystal structure of this Fc-C239i variant at 0.23 nm resolution shows that the inserted cysteine structurally replaces Ser 239 and that this causes a domino-like backward shift of the local polypeptide, pushing Pro 238 out into the hinge. Proline is unable to substitute conformationally for the wild-type glycine at this position, providing a structural reason for the previously observed abolition of both FcγR binding and antibody-dependent cellular cytotoxicity. Energy estimates for the both the FcγR interface (7 kcal/mol) and for the differential conformation of proline (20 kcal/mol) are consistent with the observed disruption of FcγR binding, providing a quantifiable case where strain at a single residue appears to disrupt a key biological function. Conversely, the structure of Fc-C239i is relatively unchanged at the intersection of the CH2 and CH3 domains; the site known to be involved in binding of the neonatal Fc receptor (FcRn), and an alignment of the Fc-C239i structure with an Fc structure in a ternary Fc:FcRn:HSA (human serum albumin) complex implies that these favorable contacts would be maintained. Hydrogen deuterium exchange mass spectroscopy (HDX-MS) data further suggest a significant increase in conformational mobility for the Fc-C239i protein relative to Fc that is evident even far from the insertion site but still largely confined to the CH2 domain. Together, the findings provide a detailed structural and dynamic basis for previously observed changes in ADC functional binding to FcγR, which may guide further development of ADC designs. Full article

Though the association between sleep duration and obesity has been generally acknowledged, there is little information about the mechanisms behind this association. The purpose of this study was to examine the effect of the fat intake and stress variables on the association between sleep duration and abdominal obesity. Data for 13,686 subjects aged ≥ 20 years from the 2013–2017 Korea National Health and Nutrition Examination Survey were used, and hierarchical and stratified logistic regression analyses were employed. In the hierarchical logistic regression analyses, fat intake and stress did not change the significance or the size of the sleep effects upon abdominal obesity. These results suggest that sleep duration does not affect abdominal obesity through fat intake or stress variables. In addition, fat intake and stress are not mediators of the sleep duration variable. However, subjects with different levels of fat intake and stress showed different associations between sleep duration and abdominal obesity. Subjects who were in the lowest or highest group of fat intake as well as self-reported stress level showed a weaker relationship between sleep duration and abdominal obesity, compared with the other groups. In conclusion, fat intake and stress modify the effects of sleep duration on abdominal obesity according to the stratified regression results. Full article

In this study, the photocatalytic degradation of azo dye “Food Black 1” (FB1) was investigated using TiO₂ and ZnO nanoparticles under ultraviolet (UV) light. The performances of the two photocatalysts were evaluated in terms of key parameters (e.g., decolorization, dearomatization, mineralization, and detoxification of dye) in relation to variables including pre-adsorption period, pH, and temperature. Under acidic conditions (pH 5), the ZnO catalyst underwent photocorrosion to increase the concentration of zinc ions in the system, thereby increasing the toxic properties of the treated effluent. In contrast, TiO₂ efficiently catalyzed the degradation of the dye at pH 5 following the Langmuir–Hinshelwood (L–H) kinetic model. The overall results of this study indicate that the decolorization rate of TiO₂ on the target dye was far superior to ZnO (i.e., by 1.5 times) at optimum catalyst loading under UV light. Full article

Obesity is a serious problem for both the individual and society due to its health and economic consequences. Therefore, there is a need to focus on factors which explain this phenomenon and may be useful in preventing future occurrence. The aim of this study was to determine the lifestyle factors coexisting with increased body mass index (BMI ≥ 25 kg/m²) in Polish adults, including factors related to diet (dietary patterns—DPs; dietary restrictions; number of meals; frequency of snacking, eating out, and ordering home delivery meals), physical activity, and sociodemographic characteristics. A cross-sectional quantitative survey was carried out in 2016 amongst 972 Polish adults under the Life Style Study (LSS). To determine the factorscoexisting with BMI ≥ 25 kg/m², the logistic regression model was developed. Women were less likely to be overweight or obese compared to men. The likelihood of BMI ≥ 25 kg/m² increased with age by 4% in each subsequent year of life. Frequent consumption of fruits and vegetables, adhering to restrictions in quantity of food consumed and at least moderate physical activity during leisure time decreased the likelihood of BMI ≥ 25 kg/m². More frequent consumption of meat and eating five or more meals a day increased the likelihood of BMI ≥ 25 kg/m². Diet-related factors explained the developed model better than factors related to physical activity, however, age and gender were the factors most strongly correlated with BMI ≥ 25 kg/m². Therefore, development of strategies to prevent and reduce overweight and obesity should focus on the demographic characteristics of the population, and then on teaching behaviors conducive for reducing the amount of food consumed, especially meat. However, physical activity in leisure time should also be included in the prevention of obesity. Full article

There have only been a limited number of analyses of soil–steel bridges under seismic and anthropogenic (rockburst) excitations. Rockbursts are phenomena similar to low-intensity natural earthquakes. They can be observed in Poland (Upper and Lower Silesia) as well as in many parts of the world where coal and gas are mined. The influence of rockbursts and natural earthquakes on soil–steel bridges should be investigated because the ground motions caused by these two kinds of excitations differ. In the present paper, a non-linear analysis of a soil–steel bridge was carried out. Expanded polystyrene (EPS) geofoam blocks were used in a numerical model of the soil–steel bridge to buffer the seismic wave induced by a rockburst (coming from a coal mine) as well as a natural earthquake (El Centro record). The analyzed soil–steel bridge had two closed pipe arches in its cross-section. The span of the shells was 4.40 m and the height of the shells was 2.80 m. The numerical analysis was conducted using the DIANA program based on the finite element method (FEM). The paper presents the FEM results of a 3D numerical study of a soil–steel bridge both with and without the application of the EPS geofoam under seismic excitations. The obtained results can be interesting to bridge engineers and scientists dealing with the design and analysis of bridges situated in seismic and mining areas. Full article

In this work, a two-phase system composed of hydrophobic ionic liquid (IL) and water phases was introduced to prepare copper sulfide (CuS) nanoparticles. It was found that CuS particles generated from the interfaces of carboxyl-functionalized IL and sodium sulfide (Na₂S) aqueous solution were prone to aggregate into nanoplates and those produced from the interfaces of carboxyl-functionalized IL and thioacetamide (TAA) aqueous solution tended to aggregate into nanospheres. Both the CuS nanoplates and nanospheres exhibited a good absorption ability for ultraviolet and visible light. Furthermore, the CuS nanoplates and nanospheres showed highly efficient photocatalytic activity in degrading rhodamine B (RhB). Compared with the reported CuS nanostructures, the CuS nanoparticles prepared in this work could degrade RhB under natural sunlight irradiation. Finally, the production of CuS from the interfaces of hydrophobic IL and water phases had the advantages of mild reaction conditions and ease of operation. Full article

We propose an open loop voltage amplifier topology based on a single JFET front-end for the realization of very low noise voltage amplifiers to be used in the field of low frequency noise measurements. With respect to amplifiers based on differential input stages, a single transistor stage has, among others, the advantage of a lower background noise. Unfortunately, an open loop approach, while simplifying the realization, has the disadvantage that because of the dispersions in the characteristics of the active device, it cannot ensure that a well-defined gain be obtained by design. To address this issue, we propose to add two simple operational amplifier-based auxiliary amplifiers with known gain as part of the measurement chain and employ cross correlation for the calibration of the gain of the main amplifier. With proper data elaboration, gain calibration and actual measurements can be carried out at the same time. By using the approach we propose, we have been able to design a low noise amplifier relying on a simplified hardware and with background noise as low as 6 nV/√Hz at 200 mHz, 1.7 nV/√Hz at 1 Hz, 0.7 nV/√Hz at 10 Hz, and less than 0.6 nV/√Hz at frequencies above 100 Hz. Full article

Nine monoamides were synthesized from carboxylic acids (C8–C18) and crude glycerol. The final monoamides were the result of a rearrangement of the acyl chain during the final hydrogenation process. The purity of the final compounds was determined by spectroscopic and mass spectrometry (MS) techniques. The thermophysical properties of solid monoamides were investigated to determine their capability to act as phase change materials (PCM) in thermal energy storage. Thermophysical properties were determined with a differential scanning calorimeter (DSC). The melting temperatures of the analyzed material ranged from 62.2 °C to 116.4 °C. The analyzed enthalpy of these monoamides ranged from 25.8 kJ/kg to 149.7 kJ/kg. Enthalpy values are analyzed considering the carbon chain and the formation of hydrogen bonds. Full article