Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular Immunotherapy Targeting Cancer Stem Cells: Preclinical Evidence and Clinical Perspective

The term “cancer stem cells” (CSCs) commonly refers to a subset of tumor cells endowed with stemness features, potentially involved in chemo-resistance and disease relapses. CSCs may present peculiar immunogenic features influencing their homeostasis within the tumor microenvironment. The susceptibility of CSCs to recognition and targeting by the immune system is a relevant issue and matter of investigation, especially considering the multiple emerging immunotherapy strategies. Adoptive cellular immunotherapies, especially those strategies encompassing the genetic redirection with chimeric antigen receptors (CAR), hold relevant promise in several tumor settings and might in theory provide opportunities for selective elimination of CSC subsets. Initial dedicated preclinical studies are supporting the potential targeting of CSCs by cellular immunotherapies, indirect evidence from clinical studies may be derived and new studies are ongoing. Here we review the main issues related to the putative immunogenicity of CSCs, focusing on and highlighting the existing evidence and opportunities for cellular immunotherapy approaches with T and non-T antitumor lymphocytes.
Macrophage Plasticity and Function in the Lung Tumour Microenvironment Revealed in 3D Heterotypic Spheroid and Explant Models

In non-small cell lung cancer (NSCLC), stroma-resident and tumour-infiltrating macrophages may facilitate an immunosuppressive tumour microenvironment (TME) and hamper immunotherapeutic responses. Analysis of tumour-associated macrophage (TAM) plasticity in NSCLC is largely lacking. We established a novel, multi-marker, dual analysis approach for assessing monocyte-derived macrophage (Mφ) polarisation and M1/M2 phenotypic plasticity. We developed a flow cytometry-based, two-marker analysis (CD64 and CD206) of CD14+ cells. The phenotype and immune function of in vitro-induced TAMs was studied in a heterotypic spheroid and tumour-derived explant model of NSCLC. Heterotypic spheroids and NSCLC explants skewed Mφs from an M1- (CD206loCD64hi) to M2-like (CD206hiCD64lo) phenotype. Lipopolysaccharide (LPS) and IFNγ treatment reversed M2-like Mφ polarisation, indicating the plasticity of Mφs. Importantly, antigen-specific CD8+ T cell responses were reduced in the presence of tumour explant-conditioned Mφs, but not spheroid-conditioned Mφs, suggesting explants are likely a more relevant model of the immune TME than cell line-derived spheroids. Our data indicates the importance of multi-marker, functional analyses within Mφ subsets and the advantages of the ex vivo NSCLC explant model in immunomodulation studies. We highlight the plasticity of the M1/M2 phenotype using the explant model and provide a tool for studying therapeutic interventions designed to reprogram M2-like Mφ-induced immunosuppression.
Microbial Diversity of Psychrotolerant Bacteria Isolated from Wild Flora of Andes Mountains and Patagonia of Chile towards the Selection of Plant Growth-Promoting Bacterial Consortia to Alleviate Cold Stress in Plants

Cold stress decreases the growth and productivity of agricultural crops. Psychrotolerant plant growth-promoting bacteria (PGPB) may protect and promote plant growth at low temperatures. The aims of this study were to isolate and characterize psychrotolerant PGPB from wild flora of Andes Mountains and Patagonia of Chile and to formulate PGPB consortia. Psychrotolerant strains were isolated from 11 wild plants (rhizosphere and phyllosphere) during winter of 2015. For the first time, bacteria associated with Calycera, Orites, and Chusquea plant genera were reported. More than 50% of the 130 isolates showed ≥33% bacterial cell survival at temperatures below zero. Seventy strains of Pseudomonas, Curtobacterium, Janthinobacterium, Stenotrophomonas, Serratia, Brevundimonas, Xanthomonas, Frondihabitans, Arthrobacter, Pseudarthrobacter, Paenarthrobacter, Brachybacterium, Clavibacter, Sporosarcina, Bacillus, Solibacillus, Flavobacterium, and Pedobacter genera were identified by 16S rRNA gene sequence analyses. Ten strains were selected based on psychrotolerance, auxin production, phosphate solubilization, presence of nifH (nitrogenase reductase) and acdS (1-aminocyclopropane-1-carboxylate (ACC) deaminase) genes, and anti-phytopathogenic activities. Two of the three bacterial consortia formulated promoted tomato plant growth under normal and cold stress conditions. The bacterial consortium composed of Pseudomonas sp. TmR5a & Curtobacterium sp. BmP22c that possesses ACC deaminase and ice recrystallization inhibition activities is a promising candidate for future cold stress studies.
Ultrafiltration Process in Disinfection and Advanced Treatment of Tertiary Treated Wastewater

The paper presents the results of research on the use of ultrafiltration, using membranes of 200 and 400 kDa separation, for disinfection of municipal treated wastewater. The research was conducted on a fractional technical scale using real municipal treated wastewater from two large wastewater treatment plants treating most of the wastewater over the one-million polycentric Gdańsk agglomeration (1.2 million inhabitants). UF 200 kDa and UF 400 kDa processes enabled further improvement of the physical and chemical parameters of treated wastewater. Total phosphorus (to below 0.2 mg/L–UF 200 kDa, 0.13 mg/L–UF 400 kDa) and turbid substances (to below 0.2 mg/L, both membranes) were removed in the highest degree. COD was reduced efficiently (to below 25.6 mgO2/L–UF 200 kDa, 26.8 mgO2/L–UF 400 kDa), while total nitrogen was removed to a small extent (to 7.12 mg/L–UF 200 kDa and 5.7 mg/L–UF 400 kDa. Based on the reduction of indicator bacteria; fecal coliforms including E. coli (FC) and fecal enterococci (FE) it was found that the ultrafiltration is an effective method of disinfection. Not much indicator bacterial were observed in the permeate after processes (UF 200 kDa; FC—5 CFU/L; FE—1 CFU/L and UF 400 kDa; FC—70 CFU/L; FE—10 CFU/L. However, microscopic analysis of prokaryotic cells and virus particles showed their presence after the application of both membrane types; TCN 3.0 × 102 cells/mL–UF 200 kDa, 5.0 × 103 cells/mL–UF 400 kDa, VP 1.0 × 105/mL. The presence of potentially pathogenic, highly infectious virus particles means that ultrafiltration cannot be considered a sufficient disinfection method for treated wastewater diverted for reuse or discharged from high load wastewater treatment plants to recreational areas. For full microbiological safety it would be advisable to apply an additional disinfection method (e.g., ozonation).
Biomarkers of Deoxynivalenol Toxicity in Chickens with Special Emphasis on Metabolic and Welfare Parameters

Deoxynivalenol (DON), a trichothecene mycotoxin produced by Fusarium species, is the most widespread mycotoxin in poultry feed worldwide. Long term-exposure from low to moderate DON concentrations can produce alteration in growth performance and impairment of the health status of birds. To evaluate the efficacy of mycotoxin-detoxifying agent alleviating the toxic effects of DON, the most relevant biomarkers of toxicity of DON in chickens should be firstly determined. The specific biomarker of exposure of DON in chickens is DON-3 sulphate found in different biological matrices (plasma and excreta). Regarding the nonspecific biomarkers called also biomarkers of effect, the most relevant ones are the impairment of the productive parameters, the intestinal morphology (reduction of villus height) and the enlargement of the gizzard. Moreover, the biomarkers of effect related to physiology (decrease of blood proteins, triglycerides, hemoglobin, erythrocytes, and lymphocytes and the increase of alanine transaminase (ALT)), immunity (response to common vaccines and release of some proinflammatory cytokines) and welfare status of the birds (such as the increase of Thiobarbituric acid reactive substances (TBARS) and the stress index), has been reported. This review highlights the available information regarding both types of biomarkers of DON toxicity in chickens.
The Use and Impact of Cognitive Enhancers among University Students: A Systematic Review

Introduction: Cognitive enhancers (CEs), also known as “smart drugs”, “study aids” or “nootropics” are a cause of concern. Recent research studies investigated the use of CEs being taken as study aids by university students. This manuscript provides an overview of popular CEs, focusing on a range of drugs/substances (e.g., prescription CEs including amphetamine salt mixtures, methylphenidate, modafinil and piracetam; and non-prescription CEs including caffeine, cobalamin (vitamin B12), guarana, pyridoxine (vitamin B6) and vinpocetine) that have emerged as being misused. The diverted non-prescription use of these molecules and the related potential for dependence and/or addiction is being reported. It has been demonstrated that healthy students (i.e., those without any diagnosed mental disorders) are increasingly using drugs such as methylphenidate, a mixture of dextroamphetamine/amphetamine, and modafinil, for the purpose of increasing their alertness, concentration or memory. Aim: To investigate the level of knowledge, perception and impact of the use of a range of CEs within Higher Education Institutions. Methodology: A systematic review was conducted in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Whilst 1400 studies were identified within this study through a variety of electronic databases (e.g., 520 through PubMed, 490 through Science Direct and 390 through Scopus), 48 papers were deemed relevant and were included in this review. Results: The most popular molecules identified here included the stimulant CEs, e.g., methylphenidate, modafinil, amphetamine salt mixtures and caffeine-related compounds; stimulant CEs’ intake was more prevalent among males than females; drugs were largely obtained from friends and family, as well as via the Internet. It is therefore suggested that CEs are increasingly being used among healthy individuals, mainly students without any diagnosed cognitive disorders, to increase their alertness, concentration, or memory, in the belief that these CEs will improve their performance during examinations or when studying. The impact of stimulant CEs may include tolerance, dependence and/or somatic (e.g., cardiovascular; neurological) complications. Discussion: The availability of CEs for non-medical indications in different countries is influenced by a range of factors including legal, social and ethical factors. Considering the risk factors and motivations that encourage university students to use CE drugs, it is essential to raise awareness about CE-related harms, counteract myths regarding “safe” CE use and address cognitive enhancement in an early stage during education as a preventative public health measure.
Phosphorus recovery through struvite precipitation from wastewater: effect of the competitive ions

AbstractIn wastewater treatment plants (WWTP), struvite precipitation occurs spontaneously under conditions which are influenced by factors such as: concentration of Mg2+, and , pH, temperature, and competitive ions. These parameters are often difficult to control and, spontaneous precipitation of struvite creates operational problems in WWTP. Struvite is also a potentially marketable product as a fertilizer alternative. For these two reasons it is important to study the principles of struvite precipitation, and evaluate the parameters that control this process. In this study, the influence of the ions Ca2+ and Al3+ in struvite precipitation process was evaluated using three different molar ratios of Mg2+:Ca2+ and Mg2+:Al3+. The products were characterized by thermogravimetric analysis, X-ray diffraction, and scanning electron micrograph. The results showed that calcium interfered in struvite precipitation only when this is in equal or greater molar ratios to magnesium, while aluminum inhibited completely.
STUDIES ON PHYTOCHROME PHOTOCONVERSIONS IN VITRO WITH LASER‐INDUCED OPTOACOUSTIC SPECTROSCOPY *

After excitation at room temperature with a 15 ns dye laser pulse, phytochrome (60 kDalton) from etiolated oat seedlings was studied by optoacoustic spectroscopy, which records the heat emission caused by non‐radiative deactivation processes of the photoexcited molecule. The action spectrum for the heat emitted by Pr deviates from the absorption spectrum around 610 and 695 nm, indicating the build‐up of photoproduct(s) within 15 ns after excitation. It is proposed that the 695 nm product is identical with I700 and lumi‐R known to be the first intermediate on the Pr× Pfr pathway, and that the photochemical back reaction of I700 to Pr occurs on the same time scale. About 90% of the absorbed light energy was lost by radiationless deactivation. Values for the rate constants of excited state deactivation of Pr and for the internal energy content difference of the primary photoproducts are calculated.
TiO2 as a Photocatalyst for Water Splitting—An Experimental and Theoretical Review

Hydrogen produced from water using photocatalysts driven by sunlight is a sustainable way to overcome the intermittency issues of solar power and provide a green alternative to fossil fuels. TiO2 has been used as a photocatalyst since the 1970s due to its low cost, earth abundance, and stability. There has been a wide range of research activities in order to enhance the use of TiO2 as a photocatalyst using dopants, modifying the surface, or depositing noble metals. However, the issues such as wide bandgap, high electron-hole recombination time, and a large overpotential for the hydrogen evolution reaction (HER) persist as a challenge. Here, we review state-of-the-art experimental and theoretical research on TiO2 based photocatalysts and identify challenges that have to be focused on to drive the field further. We conclude with a discussion of four challenges for TiO2 photocatalysts—non-standardized presentation of results, bandgap in the ultraviolet (UV) region, lack of collaboration between experimental and theoretical work, and lack of large/small scale production facilities. We also highlight the importance of combining computational modeling with experimental work to make further advances in this exciting field.
Molecular Structure-Based Prediction of the Toxicokinetics of Inhaled Vapors in Humans

The objectives of the present study were: (1) to evaluate the adequacy of setting hepatic extraction ratio (E) equal to 0 or 1 in physiologically based toxicokinetic (PBTK) models to generate the theoretically plausible envelope of venous blood concentration (Cv) profiles, and (2) to couple this approach with molecular structure-based estimation of blood:air and tissue: blood partition coefficients (PCs) to predictthe Cv profiles of volatile organic chemicals (VOCs) in humans. Setting E= 0 or 1 in PBTK models provided simulations of Cv envelopes that contained the Cv values determined in humans exposed to low concentrations of dichloromethane(DCM), ethylbenzene (EBZ), toluene (TOL), m-xylene(XYL), trichloroethy-lene (TCE), and 1,1,1-trichloroethane(TRI). Following the validation of using E= 0 or 1 in conventional PBTK models to predict the theoretically plausible envelope of Cv, a quantitative structure-toxicokinetic relationship (QSTkR) model was constructed. The QSTkR model used molecular structure information as the sole input to predict the PCs and considered E= 0 or 1 to generate simulations of the envelope of Cv. The experimental data on Cv were in most cases within the envelopes simulated using QSTkR models for DCM, EBZ, TOL, and XYL, but were outside the envelopes for TCE and TRI. The discrepancy observed between the Cv envelopes obtained using PBTK and QSTkR models can be explained by the fact that blood:air PCs of some VOCs were under-predicted while using molecular structure information. The modeling framework presented in this article represents the first animal-replacement tool that can provide a priori predictions of the toxicokinetic profiles of VOCs prior to laboratory experiments.
Molecular Markers of Antifungal Resistance: Potential Uses in Routine Practice and Future Perspectives

Antifungal susceptibility testing (AST) has come to establish itself as a mandatory routine in clinical practice. At the same time, the mycological diagnosis seems to have headed in the direction of non-culture-based methodologies. The downside of these developments is that the strains that cause these infections are not able to be studied for their sensitivity to antifungals. Therefore, at present, the mycological diagnosis is correctly based on laboratory evidence, but the antifungal treatment is undergoing a growing tendency to revert back to being empirical, as it was in the last century. One of the explored options to circumvent these problems is to couple non-cultured based diagnostics with molecular-based detection of intrinsically resistant organisms and the identification of molecular mechanisms of resistance (secondary resistance). The aim of this work is to review the available molecular tools for antifungal resistance detection, their limitations, and their advantages. A comprehensive description of commercially available and in-house methods is included. In addition, gaps in the development of these molecular technologies are discussed.
Metabolites Secreted by Bovine Embryos In Vitro Predict Pregnancies That the Recipient Plasma Metabolome Cannot, and Vice Versa

This work describes the use of mass spectrometry-based metabolomics as a non-invasive approach to accurately predict birth prior to embryo transfer (ET) starting from embryo culture media and plasma recipient. Metabolomics was used here as a predictive platform. Day-6 in vitro produced embryos developed singly in modified synthetic oviduct fluid culture medium (CM) drops for 24 h were vitrified as Day-7 blastocysts and transferred to recipients. Day-0 and Day-7 recipient plasma (N = 36 × 2) and CM (N = 36) were analyzed by gas chromatography coupled to the quadrupole time of flight mass spectrometry (GC-qTOF). Metabolites quantified in CM and plasma were analyzed as a function to predict pregnancy at Day-40, Day-62, and birth (univariate and multivariate statistics). Subsequently, a Boolean matrix (F1 score) was constructed with metabolite pairs (one from the embryo, and one from the recipient) to combine the predictive power of embryos and recipients. Validation was performed in independent cohorts of ETs analyzed. Embryos that did not reach birth released more stearic acid, capric acid, palmitic acid, and glyceryl monostearate in CM (i.e., (p < 0.05, FDR < 0.05, Receiver Operator Characteristic—area under curve (ROC-AUC) > 0.669)). Within Holstein recipients, hydrocinnamic acid, alanine, and lysine predicted birth (ROC-AUC > 0.778). Asturiana de los Valles recipients that reached birth showed lower concentrations of 6-methyl-5-hepten-2-one, stearic acid, palmitic acid, and hippuric acid (ROC-AUC > 0.832). Embryonal capric acid and glyceryl-monostearate formed F1 scores generally >0.900, with metabolites found both to differ (e.g., hippuric acid, hydrocinnamic acid) or not (e.g., heptadecanoic acid, citric acid) with pregnancy in plasmas, as hypothesized. Efficient lipid metabolism in the embryo and the recipient can allow pregnancy to proceed. Changes in phenolics from plasma suggest that microbiota and liver metabolism influence the pregnancy establishment in cattle.
Discovery of Screening Biomarkers for Major Depressive Disorder in Remission by Proteomic Approach

Major depressive disorder (MDD) is a common disorder involving depressive mood and decreased motivation. Due to its high heterogeneity, novel biomarkers are required to diagnose MDD. In this study, a proteomic method was used to identify a new MDD biomarker. Using sequential window acquisition of all theoretical mass spectra acquisitions and multiple reaction monitoring analysis via mass spectrometry, relative and absolute quantification of proteins in the sera was performed. The results of the relative quantitation by sequential window acquisition for all theoretical mass spectra data showed that seven proteins were significantly differently expressed between MDD patients and other patients with remission status. However, absolute quantification by multiple reaction monitoring analysis identified prothrombin as the only significantly upregulated protein in the depressive state compared to remission (p < 0.05) and was, thus, subsequently selected as an MDD biomarker. The area under the curve for prothrombin was 0.66. Additionally, increased prothrombin/thrombin induced hyper-activation of platelets via activating protease-activated receptors, a feature associated with MDD; specifically, activated platelets secrete various molecules related to MDD, including brain-derived neurotropic factors and serotonin. Therefore, prothrombin is a potential screening, prognostic, and diagnostic marker for MDD.
Antioxidant Therapy in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD) are a group of chronic, incurable diseases of the digestive tract, the etiology of which remains unclear to this day. IBD result in significant repercussions on the quality of patients’ life. There is a continuous increase in the incidence and prevalence of IBD worldwide, and it is becoming a significant public health burden. Pharmaceuticals commonly used in IBD management, for example, mesalamine, sulfasalazine, corticosteroids, and others, expose patients to diverse, potentially detrimental side effects and frequently do not provide sufficient disease control. The chronic inflammation underlies the etiology of IBD and closely associates with oxidative/nitrosative stress and a vast generation of reactive oxygen/nitrogen species. Relative to this, several substances with antioxidant and anti-inflammatory properties are now intensively researched as possible adjunctive or independent treatment options in IBD. Representatives of several different groups, including natural and chemical compounds will be characterized in this dissertation.
Different Cannabis sativa Extraction Methods Result in Different Biological Activities against a Colon Cancer Cell Line and Healthy Colon Cells

Cannabis sativa is one of the oldest medicinal plants used by humans, containing hundreds of bioactive compounds. The biological effects and interplay of these compounds are far from fully understood, although the plant’s therapeutic effects are beyond doubt. Extraction methods for these compounds are becoming an integral part of modern Cannabis-based medicine. Still, little is known about how different methods affect the final composition of Cannabis extracts and thus, their therapeutic effects. In this study, different extraction methods were tested, namely maceration, Soxhlet, ultrasound-assisted extraction (UAE), and supercritical CO2 extraction methods. The obtained extracts were evaluated for their cannabinoid content, antioxidant properties, and in vitro bioactivity on human colon cancer and healthy colon cells. Our data suggest that Cannabis extracts, when properly prepared, can significantly decrease cancer cell viability while protecting healthy cells from cytotoxic effects. However, post-processing of extracts poses a significant limitation in predicting therapeutic response based on the composition of the crude extract, as it affects not only the actual amounts of the respective cannabinoids but also their relative ratio to the primary extracts. These effects must be carefully considered in the future preparations of new therapeutic extracts.