Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Simplification of Natural Products: Synthesis, Antibacterial Activity, and Molecular Docking Studies of Berberine Open Models

Berberine, the main bioactive component of many medicinal plants belonging to various genera such as Berberis, Coptis, and Hydrastis is a multifunctional compound. Among the numerous interesting biological properties of berberine is broad antimicrobial activity including a range of Gram-positive and Gram-negative bacteria. With the aim of identifying berberine analogues possibly endowed with higher lead-likeness and easier synthetic access, the molecular simplification approach was applied to the secondary metabolite and a series of analogues were prepared and screened for their antimicrobial activity against Gram-positive and Gram-negative bacterial test species. Rewardingly, the berberine simplified analogues displayed 2–20-fold higher potency with respect to berberine. Since our berberine simplified analogues may be easily synthesized and are characterized by lower molecular weight than the parent compound, they are further functionalizable and should be more suitable for oral administration. Molecular docking simulations suggested FtsZ, a well-known protein involved in bacterial cell division, as a possible target.
An Improved Modelling Approach for the Comprehensive Study of Direct Contact Membrane Distillation

Direct Contact Membrane Distillation (DCMD) is a promising and feasible technology for water desalination. Most of the models used to simulate DCMD are one-dimensional and/or use a linear function of vapour pressure which relies on experimentally determined parameters. In this study, the model of DCMD using Nusselt correlations was improved by coupling the continuity, momentum, and energy equations to better capture the downstream alteration of flow field properties. A logarithmic function of vapour pressure, which is independent from experiments, was used. This allowed us to analyse DCMD with different membrane properties. The results of our developed model were in good agreement with the DCMD experimental results, with less than 7% deviation. System performance metrics, including water flux, temperature, and concentration polarisation coefficient and thermal efficiency, were analysed by varying inlet feed and permeate temperature, inlet velocity, inlet feed concentration, channel length. In addition, twenty-two commercial membranes were analysed to obtain a real vision on the influence of membrane characteristics on system performance metrics. The results showed that the feed temperature had the most significant effect on water flux and thermal efficiency. The increased feed temperature enhanced the water flux and thermal efficiency; however, it caused more concentration and temperature polarisation. On the other hand, the increased inlet velocity was found to provide increased water flux and reduced temperature and concertation polarisation as well. It was also found that the membrane properties, especially thickness and porosity, can affect the DCMD performance significantly. A two-fold increase of feed temperature increased the water flux and thermal efficiency, 10-fold and 27%, respectively; however, it caused an increase in temperature and concertation polarisation, at 48% and 34%, respectively. By increasing Reynolds number from 80 to 1600, the water flux, CPC, and TPC enhanced by 2.3-fold, 2%, and 21%, respectively. The increased feed concentration from 0 to 250 [g/L] caused a 26% reduction in water flux. To capture the downstream alteration of flow properties, it was shown that the ratio of inlet value to outlet value of system performance metrics decreased significantly throughout the module. Therefore, improvement over the conventional model is undeniable, as the new model can assist in achieving optimal operation conditions.
Characterization of Betulinic Acid-Multiwalled Carbon Nanotubes Modified with Hydrophilic Biopolymer for Improved Biocompatibility on NIH/3T3 Cell Line

The biocompatibility of carbon nanotubes (CNT) is fairly a challenging task for their applications in nanomedicine. Therefore, the objective of this research was to formulate four types of highly biocompatible betulinic acid-loaded biopolymer nanocomposites, namely chitosan-multiwalled carbon nanotubes (MWBA-CS), polyethylene glycol-multiwalled carbon nanotubes (MWBA-PG), Tween 20-multiwalled carbon nanotubes (MWBA-T2) and Tween 80-multiwalled carbon nanotubes (MWBA-T8). The physico-chemical properties of the modified nanocomposites were determined by Fourier transform infrared spectroscopy (FTIR), thermal analysis (TGA) and Raman spectroscopy, while the surface morphology of the resulting nanocomposites was studied using field emission scanning electron microscopy (FESEM). All data revealed that the external surface of MWBA nanocomposites was successfully coated with the respective polymer molecules through hydrophobic and electrostatic interactions with improved thermal profiles. The cell viability assay, which was performed on cultured normal embryonic mouse fibroblast cells, confirmed their excellent biocompatibility in phosphate-buffered saline aqueous media. Overall, our findings herein suggest that the synthesized biopolymer-coated MWBA nanocomposites are promising nanomaterials for drug delivery applications as they enhance the solubility and dispersibility of CNT with significantly reduced cytotoxic effect, especially in normal cells.
Induction of Apoptosis, Inhibition of MCL-1, and VEGF-A Expression Are Associated with the Anti-Cancer Efficacy of Magnolol Combined with Regorafenib in Hepatocellular Carcinoma

Simple Summary The synergistic inhibition of hepatocellular carcinoma growth was induced by administering magnolol together with regorafenib, instead of each treatment individually. Hepatocellular carcinoma (HCC) cells were sensitized to regorafenib through the inhibition of the expression of both vascular endothelial growth factor A (VEGF-A) and myeloid cell leukemia 1 (MCL-1) by siRNA. Moreover, the regorafenib-induced suppression of VEGF-A and MCL-1 at the protein level was enhanced by magnolol. Extrinsic (expression of FAS, FAS-L, and cleaved-caspase-8) and intrinsic apoptotic signaling (ROS production, the accumulation of Ca2+, the loss of △ψm, and the nuclear translocation of AIF), and DNA damage were all effectively increased by regorafenib combined with magnolol. In addition, a superior inhibition of metastasis was triggered by the combination of regorafenib and magnolol. In sum, the enhancement of apoptosis induction and the suppression of the expression of VEGF-A and MCL-1 were associated with the anti-cancer efficacy of magnolol combined with regorafenib in HCC. Abstract While regorafenib was approved for the treatment of advanced HCC in 2017, with a partial response and survival benefit; other combination agents to facilitate the efficacy of regorafenib still need to be explored. Magnolol is a potential natural anti-tumor compound for many types of cancers. Combination indexes calculated on the basis of both in vitro and in vivo models have indicated a synergistic effect of the combination of regorafenib and magnolol. The overexpression of the VEGF-A protein significantly diminished regorafenib’s inhibition of cell viability, while the transient knockdown of VEGF-A by siRNA effectively sensitized HCC cells to regorafenib. In addition, the inhibition of MCL-1 by siRNA combined with regorafenib allowed for a significantly greater inhibition of cell growth, compared to regorafenib alone. A lower protein expression level for VEGF-A and MCL-1 was found for the combination treatment of HCC in vitro and in vivo. A superior metastasis inhibition was also found in the combination group, as compared to the single-treatment groups, using a transwell assay, wound healing assay, and Western blotting. The caspase-dependent and -independent and DNA damage effects, as determined by flow cytometry and a comet assay, were increased by the combination therapy. Taken together, magnolol sensitized HCC to regorafenib, which was correlated with the reduction of VEGF-A and MCL-1 and the induction of apoptosis.
Feasibility of investigating the association between bacterial pathogens and oral leukoplakia in low and middle income countries: A population-based pilot study in India

Background Certain oral bacterial pathogens may play a role in oral carcinogenesis. We assessed the feasibility of conducting a population-based study in India to examine the distributions and levels of Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia in relation to oral leukoplakia (a potentially malignant disorder) and other participant characteristics. Methods This exploratory case-control study was nested within a large urban Indian cohort and the data included 22 men and women with oral leukoplakia (cases) and 69 leukoplakia-free controls. Each participant provided a salivary rinse sample, and a subset of 34 participants (9 cases; 25 controls) also provided a gingival swab sample from keratinized gingival surface for quantitative polymerase chain reaction (qPCR). Results Neither the distribution nor the levels of pathogens were associated with oral leukoplakia; however, individual pathogen levels were more strongly correlated with each other in cases compared to controls. Among controls, the median level of total pathogens was the highest (7.55×104 copies/ng DNA) among persons of low socioeconomic status. Salivary rinse provided better DNA concentration than gingival swab for qPCR analysis (mean concentration: 1.8 ng/μl vs. 0.2 ng/μl). Conclusions This study confirms the feasibility of population studies evaluating oral microbiome in low-resource settings and identifies promising leads for future research.
Thermal Degradation Mechanism and Decomposition Kinetic Studies of Poly(Lactic Acid) and Its Copolymers with Poly(Hexylene Succinate)

Ιn this work, new block poly(lactic acid)-block-poly(hexylene succinate) (PLA-b-PHSu) copolymers, in different mass ratios of 95/05, 90/10 and 80/20 w/w, are synthesized and their thermal and mechanical behavior are studied. Thermal degradation and thermal stability of the samples were examined by Thermogravimetric Analysis (TGA), while thermal degradation kinetics was applied to better understand this process. The Friedman isoconversional method and the “model fitting method” revealed accurate results for the activation energy and the reaction mechanisms (nth order and autocatalysis). Pyrolysis-Gas Chromatography/Mass Spectrometry (Py-GC/MS) was used to provide more details of the degradation process with PHSu’s mechanism being the β-hydrogen bond scission, while on PLA the intramolecular trans-esterification processes domains. PLA-b-PHSu copolymers decompose also through the β-hydrogen bond scission. The mechanical properties have also been tested to understand how PHSu affects PLA’s structure and to give more information about this new material. The tensile measurements gave remarkable results as the elongation at break increases as the content of PHSu increases as well. The study of the thermal and mechanical properties is crucial, to examine if the new material fulfills the requirements for further investigation for medical or other possible uses that might come up.
Prediction of confirmed cases of and deaths caused by COVID-19 in Chile through time series techniques: A comparative study

Background Chile has become one of the countries most affected by COVID-19, a pandemic that has generated a large number of cases worldwide. If not detected and treated in time, COVID-19 can cause multi-organ failure and even death. Therefore, it is necessary to understand the behavior of the spread of COVID-19 as well as the projection of infections and deaths. This information is very relevant so that public health organizations can distribute financial resources efficiently and take appropriate containment measures. In this research, we compare different time series methodologies to predict the number of confirmed cases of and deaths from COVID-19 in Chile. Methods The methodology used in this research consisted of modeling cases of both confirmed diagnoses and deaths from COVID-19 in Chile using Autoregressive Integrated Moving Average (ARIMA henceforth) models, Exponential Smoothing techniques, and Poisson models for time-dependent count data. Additionally, we evaluated the accuracy of the predictions using a training set and a test set. Results The dataset used in this research indicated that the most appropriate model is the ARIMA time series model for predicting the number of confirmed COVID-19 cases, whereas for predicting the number of deaths from COVID-19 in Chile, the most suitable approach is the damped trend method. Conclusion The ARIMA models are an alternative to modeling the behavior of the spread of COVID-19; however, depending on the characteristics of the dataset, other methodologies can better predict the behavior of these records, for example, the Holt-Winter method implemented with time-dependent count data.
Role of Thrombopoietin Receptor Agonists in Inherited Thrombocytopenia

In the last decade, improvements in genetic testing have revolutionized the molecular diagnosis of inherited thrombocytopenias (ITs), increasing the spectrum of knowledge of these rare, complex and heterogeneous disorders. In contrast, the therapeutic management of ITs has not evolved in the same way. Platelet transfusions have been the gold standard treatment for a long time. Thrombopoietin receptor agonists (TPO-RA) were approved for immune thrombocytopenia (ITP) ten years ago and there is evidence for the use of TPO-RA not only in other forms of ITP, but also in ITs. We have reviewed in the literature the existing evidence on the role of TPO-RAs in ITs from 2010 to February 2021. A total of 24 articles have been included, 4 clinical trials, 3 case series and 17 case reports. A total of 126 patients with ITs have received TPO-RA. The main diagnoses were Wiskott–Aldrich syndrome, MYH9-related disorder and ANKRD26-related thrombocytopenia. Most patients were enrolled in clinical trials and were treated for short periods of time with TPO-RA as bridging therapies towards surgical interventions, or other specific approaches, such as hematopoietic stem cell transplantation. Here, we have carried out an updated and comprehensive review about the efficacy and safety of TPO-RA in ITs.
Role and Modulation of TRPV1 in Mammalian Spermatozoa: An Updated Review

Based on the abundance of scientific publications, the polymodal sensor TRPV1 is known as one of the most studied proteins within the TRP channel family. This receptor has been found in numerous cell types from different species as well as in spermatozoa. The present review is focused on analyzing the role played by this important channel in the post-ejaculatory life of spermatozoa, where it has been described to be involved in events such as capacitation, acrosome reaction, calcium trafficking, sperm migration, and fertilization. By performing an exhaustive bibliographic search, this review gathers, for the first time, all the modulators of the TRPV1 function that, to our knowledge, were described to date in different species and cell types. Moreover, all those modulators with a relationship with the reproductive process, either found in the female tract, seminal plasma, or spermatozoa, are presented here. Since the sperm migration through the female reproductive tract is one of the most intriguing and less understood events of the fertilization process, in the present work, chemotaxis, thermotaxis, and rheotaxis guiding mechanisms and their relationship with TRPV1 receptor are deeply analyzed, hypothesizing its (in)direct participation during the sperm migration. Last, TRPV1 is presented as a pharmacological target, with a special focus on humans and some pathologies in mammals strictly related to the male reproductive system.
Selective Extraction of Nonfullerene Acceptors from Bulk-Heterojunction Layer in Organic Solar Cells for Detailed Analysis of Microstructure

Detailed analyses of the microstructures of bulk-heterojunction (BHJ) layers are important for the development of high-performance photovoltaic organic solar cells (OSCs). However, analytical methods for BHJ layer microstructures are limited because BHJ films are composed of a complex mixture of donor and acceptor materials. In our previous study on the microstructure of a BHJ film composed of donor polymers and fullerene-based acceptors, we analyzed donor polymer-only films after selectively extracting fullerene-based acceptors from the film by atomic force microscopy (AFM). Not only was AFM suitable for a clear analysis of the morphology of the donor polymers in the BHJ film, but it also allowed us to approximate the acceptor morphology by analyzing the pores in the extracted films. Herein we report a method for the selective extraction of nonfullerene acceptors (NFAs) from a BHJ layer in OSCs and provide a detailed analysis of the remaining BHJ films based upon AFM. We found that butyl glycidyl ether is an effective solvent to extract NFAs from BHJ films without damaging the donor polymer films. By using the selective extraction method, the morphologies of NFA-free BHJ films fabricated under various conditions were studied in detail. The results may be useful for the optimization of BHJ film structures composed of NFAs and donor polymers.
Design and Gas Separation Performance of Imidazolium Poly(ILs) Containing Multivalent Imidazolium Fillers and Crosslinking Agents

This work introduces a series of vinyl-imidazolium-based polyelectrolyte composites, which were structurally modified via impregnation with multivalent imidazolium-benzene ionic liquids (ILs) or crosslinked with novel cationic crosslinkers which possess internal imidazolium cations and vinylimidazolium cations at the periphery. A set of eight [C4vim][Tf2N]-based membranes were prepared via UV-initiated free radical polymerization, including four composites containing di-, tri-, tetra-, and hexa-imidazolium benzene ILs and four crosslinked derivatives which utilized tri- and tetra- vinylimidazolium benzene crosslinking agents. Structural and functional characterizations were performed, and pure gas permeation data were collected to better understand the effects of “free” ILs dispersed in the polymeric matrix versus integrated ionic crosslinks on the transport behaviors of these thin films. These imidazolium PIL:IL composites exhibited moderately high CO2 permeabilities (~20–40 Barrer), a 4–7× increase relative to corresponding neat PIL, with excellent selectivities against N2 or CH4. The addition of imidazolium-benzene fillers with increased imidazolium content were shown to correspondingly enhance CO2 solubility (di- < tri- < tetra- < hexa-), with the [C4vim][Tf2N]: [Hexa(Im+)Benz ][Tf2N] composite showing the highest CO2 permeability (PCO2 = 38.4 Barrer), while maintaining modest selectivities (αCO2/CH4 = 20.2, αCO2/N2 = 23.6). Additionally, these metrics were similarly improved with the integration of more ionic content bonded to the polymeric matrix; increased PCO2 with increased wt% of the tri- and tetra-vinylimidazolium benzene crosslinking agent was observed. This study demonstrates the intriguing interactions and effects of ionic additives or crosslinkers within a PIL matrix, revealing the potential for the tuning of the properties and transport behaviors of ionic polymers using ionic liquid-inspired small molecules.
Evidence-Based Digital Tools for Weight Loss Maintenance: The NoHoW Project

Background: Effective interventions and commercial programmes for weight loss (WL) are widely available, but most people regain weight. Few effective WL maintenance (WLM) solutions exist. The most promising evidence-based behaviour change techniques for WLM are self-monitoring, goal setting, action planning and control, building self-efficacy, and techniques that promote autonomous motivation (e.g., provide choice). Stress management and emotion regulation techniques show potential for prevention of relapse and weight regain. Digital technologies (including networked-wireless tracking technologies, online tools and smartphone apps, multimedia resources, and internet-based support) offer attractive tools for teaching and supporting long-term behaviour change techniques. However, many digital offerings for weight management tend not to include evidence-based content and the evidence base is still limited. The Project: First, the project examined why, when, and how many European citizens make WL and WLM attempts and how successful they are. Second, the project employed the most up-to-date behavioural science research to develop a digital toolkit for WLM based on 2 key conditions, i.e., self-management (self-regulation and motivation) of behaviour and self-management of emotional responses for WLM. Then, the NoHoW trial tested the efficacy of this digital toolkit in adults who achieved clinically significant (≥5%) WL in the previous 12 months (initial BMI ≥25). The primary outcome was change in weight (kg) at 12 months from baseline. Secondary outcomes included biological, psychological, and behavioural moderators and mediators of long-term energy balance (EB) behaviours, and user experience, acceptability, and cost-effectiveness. Impact: The project will directly feed results from studies on European consumer behaviour, design and evaluation of digital toolkits self-management of EB behaviours into development of new products and services for WLM and digital health. The project has developed a framework and digital architecture for interventions in the context of EB tracking and will generate results that will help inform the next generation of personalised interventions for effective self-management of weight and health.
Broad-Spectrum HDAC Inhibitors Promote Autophagy through FOXO Transcription Factors in Neuroblastoma

Depending on context and tumor stage, deregulation of autophagy can either suppress tumorigenesis or promote chemoresistance and tumor survival. Histone deacetylases (HDACs) can modulate autophagy; however, the exact mechanisms are not fully understood. Here, we analyze the effects of the broad-spectrum HDAC inhibitors (HDACi) panobinostat and vorinostat on the transcriptional regulation of autophagy with respect to autophagy transcription factor activity (Transcription factor EB—TFEB, forkhead boxO—FOXO) and autophagic flux in neuroblastoma cells. In combination with the late-stage autophagic flux inhibitor bafilomycin A1, HDACis increase the number of autophagic vesicles, indicating an increase in autophagic flux. Both HDACi induce nuclear translocation of the transcription factors FOXO1 and FOXO3a, but not TFEB and promote the expression of pro-autophagic FOXO1/3a target genes. Moreover, FOXO1/3a knockdown experiments impaired HDACi treatment mediated expression of autophagy related genes. Combination of panobinostat with the lysosomal inhibitor chloroquine, which blocks autophagic flux, enhances neuroblastoma cell death in culture and hampers tumor growth in vivo in a neuroblastoma zebrafish xenograft model. In conclusion, our results indicate that pan-HDACi treatment induces autophagy in neuroblastoma at a transcriptional level. Combining HDACis with autophagy modulating drugs suppresses tumor growth of high-risk neuroblastoma cells. These experimental data provide novel insights for optimization of treatment strategies in neuroblastoma.