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Bogusz Jan Aksak-Wąs,1 Agnieszka Ripa,2 Paweł Szakoła,3 Karolina Horbacka,3 Jolanta Niścigorska-Olsen,2 Magdalena Witak-Jędra,2 Małgorzata Zając-Marczewska,2 Malwina Karasińska-Cieślak,2 Jacek Kot,4 Miłosz Parczewski1 1Department of Infectious, Tropical Diseases and Immune Deficiency, Pomeranian Medical University in Szczecin, Szczecin, Poland; 2Department of Infectious, Tropical Diseases and Immune Deficiency, Provincial Hospital, Szczecin, Poland; 3Department of General and Transplant Surgery, Department of Vascular Surgery, Provincial Hospital, Szczecin, Poland; 4National Center for Hyperbaric Medicine, University Center for Maritime and Tropical Medicine in Gdynia, Medical University of Gdansk, Gdansk, PolandCorrespondence: Bogusz Jan Aksak-Wąs Email bogusz.aw@gmail.comIntroduction: Vibrio vulnificus infections are a growing problem worldwide. In recent years, infections with this bacteria have been reported in Central Europe, especially in the German Baltic coast but also in France and Italy. Climate warming causes the sea temperature to increase every year, which translates to an increased risk of infections from the Vibrio group. Most of these are mild and present as wound infections, but some patients develop life-threatening sepsis from either ingestion of infected mollusks or wound lesions that develop into generalized infections. Illness may be associated with necrotizing fasciitis and may require several weeks of therapy, often based on a surgical operation, demarcation of necrosis or limb amputation. A case such as the one described in this manuscript has not been previously described in Poland and demonstrates the need for a multidisciplinary approach to infection with Vibrio vulnificus.Case Presentation: A 68-year-old patient was pricked with an unknown object in the side of a lower limb during his stay at the Polish seaside. He developed a life-threatening infection in the form of severe sepsis with multiple organ failure. He required broad-spectrum antibiotic therapy, and after obtaining results for Vibrio vulnificus targeted therapy, a surgical operation with skin lesion decompression and fasciotomy was performed. Finally, hyperbaric chamber therapy was given. The patient’s general condition improved, and local changes and his vital parameters stabilized.Conclusion: Vibrio vulnificus infection may be confused with other causes of skin and subcutaneous tissue infection, although it requires a different approach and different targeted antibiotic therapies. This infection may take the form of a life-threatening disease requiring a multidisciplinary approach.Keywords: case report, Vibrio vulnificus, sepsis shock, crustaceans, hyperbaric chamber

Aerogels are characterized by excellent insulation properties and a good resistance to high and low temperatures. The objective of this study was to investigate the effects of silica aerogel on thermal properties of textile–polymer composites. Aerogel was applied in protective clothing fabric to improve its heat resistance. The composites were produced by coating a fabric made of meta-aramid (polyamide–imide) yarns with a dispersion of polychloroprene latex and synthetic resins or an acrylic–styrene dispersion with aerogel (100–700 μm particle size). The composites were subjected to thermal radiation (20 kW/m2) and their thermal properties were determined by thermogravimetry/derivative thermogravimetry (TG/DTG). Scanning electron microscopy/X-ray energy dispersive spectroscopy (SEM/EDS) was used to characterize the microstructure and study the elemental composition of materials. The thermal conductivity and resistance of composites were measured with an Alambeta apparatus. The tests indicated an increase in resistance to thermal radiation by approximately 15–25%. In TG/DTG analysis, the initial temperature for an unmodified fabric was 423.3°C. After modification, it decreased to 361.8° and 365.3°C for composites with 7 and 14% of aerogel, respectively. SEM images revealed a reduction in aerogel particle size.

Jan Klata’s Shakespearean productions are famous for his liberal attitude to the text, innovative sets and locations, and a strong contemporary context. His 2004 H., a Teatr Wybrzeże production performed in the Gdańsk Shipyard, reaches to the Polish history of the eighties (the importance of Solidarity and the fall of communism) to comment on the state of the democratic Poland twenty years later. The 2012 Titus Andronicus, a coproduction of Teatr Polski in Wrocław and Staatsschauspiel Dresden, explores the impact of historical traumas on national prejudice and relations within the new Europe. The 2013 Hamlet with Schauspielhaus Bochum again tries to diagnose the contemporary condition and is again deeply rooted in a specific geopolitical context.

Bogusz Aksak-Wąs, Malwina Karasińska-Cieślak, Miłosz Parczewski Department of Infectious, Tropical Diseases and Acquired Immunodeficiency, Pomeranian Medical University in Szczecin, Szczecin, PolandCorrespondence: Bogusz Aksak-Wąs, Email bogusz.aksak.was@pum.edu.plAbstract: This case report provides data on unique challenges related to amoebiasis diagnostics and treatment in non-endemic regions. The presented case report is focused a 28-year-old male patient of Indian origin, temporarily living in Poland, who was diagnosed with an amoebic liver abscess. The patient presented with a range of non-specific symptoms including shortness of breath, chest pain, and fever. The differential diagnosis included cardio-pulmonary diseases, a range of tropical diseases such as malaria or typhoid fever, bacterial abscesses, and malignancies, necessitating a comprehensive, multi-modal diagnostic approach. This approach included an extensive review of patient history, physical examination, and various laboratory and imaging investigations. A further challenge in this case was the unavailability of standard cysticidal treatments in Poland, which required individualized therapeutic strategy. Despite these obstacles, the patient was successfully treated using an alternative regimen of intravenous metronidazole, ceftriaxone, doxycycline, chloroquine, and finally, trimethoprim/sulfamethoxazole (treatment with metronidazole was used as a base drug, due to the lack of typical cysticidal treatment, an alternative treatment was added: chloroquine is a recommended drug used in the treatment of pregnant patients, in addition, doxycycline showed in vitro activity against Entamoeba histolytica). This therapeutic journey underscored the value of adaptability in treatment protocols, particularly in regions where certain resources may not be readily available. This case report underlines the importance of broadening the differential diagnosis in non-endemic regions to include tropical diseases, particularly in the context of increasing global travel and migration. It also highlights the significance of employing comprehensive diagnostic strategies and adaptable treatment protocols in such scenarios. In addition, the report reiterates the need for global collaboration and education among healthcare providers to effectively manage tropical diseases, especially in non-endemic regions. Through its exploration of the complexities associated with diagnosing and managing amebiasis in a non-endemic region, this report offers valuable insights to clinicians worldwide.Keywords: amoebiasis, non endemic region, abscess, tropical disease

Abstract Background Cysteinyl leukotrienes are potent inflammatory mediators implicated in the pathogenesis of asthma. Human cysteinyl leukotriene receptor 1 (CYSLTR1) gene contains five exons that are variably spliced. Within its promoter few polymorphisms were described. To date, there has been no evidence about the expression of different splice variants of CysLT1 in asthma and their association with CYSLTR1 promoter polymorphisms. The goal of our study was to investigate CysLT1 alternative transcripts expression in asthmatic patients with different CYSLTR1 promoter haplotypes. The study groups consisted of 44 patients with asthma, diagnosed according to GINA 2008 criteria and 18 healthy subjects. Genomic DNA and total RNA was extracted from peripheral blood mononuclear cells. Real-time PCR was performed with specific primers for transcript I [GenBank:DQ131799] and II [GenBank:DQ131800]. Fragments of the CYSLTR1 promoter were amplified by PCR and sequenced directly to identify four single nucleotide polymorphisms: C/T [SNP:rs321029], A/C [SNP:rs2637204], A/G [SNP:rs2806489] and C/T [SNP:rs7066737]. Results The expression of CysLT1 transcript I and II in asthma did not differ from its expression in healthy control group. However, in major alleles homozygotic CAAC/CAAC women with asthma we found significantly higher expression of transcript I as compared to heterozygous CAAC/TCGC women in that loci. CysLT1 transcript I expression tended to negative correlation with episodes of acute respiratory infection in our asthmatic population. Moreover, expression of CysLT1 transcript II in CAAC/CAAC homozygotic women with asthma was significantly lower than in CAAC/CAAC healthy control females. Conclusions Genetic variants of CYSLTR1 promoter might be associated with gender specific expression of CysLT1 alternative transcripts in patients with asthma. CysLT1 splice variants expression might also correlate with the susceptibility to infection in asthmatic population.

Abstract Background SCF (stem cell factor) is a pleiotropic cytokine exerting its role at different stages of bone marrow development and affecting eosinophil activation, mast cells and basophil chemotaxis and survival. The aim of the study was to assess concentration of SCF and its soluble receptor c-kit (sc-kit) in peripheral blood of patients with asthma referring it to asthma severity and phenotype. Methods The study involved 107 patients with bronchial asthma, well characterized with respect to severity and 21 healthy controls. Concentration of SCF and sc-kit in the patients serum were measured by ELISA method. Results Mean serum SCF level in the group of asthmatics (n = 88) was significantly higher as compared to healthy controls (1010 pg/ml ± 37 vs 799 ± 33; p < 0,001). The level of SCF was higher in patients with severe asthma as compared to patients with non-severe asthma (1054 +/- 41 pg/ml vs 819 +/- 50; p < 0,01) and correlated with dose of inhaled glucocorticosteroids taken by the patients to achieve asthma control (R = 0,28; p < 0,01). The mean sc-kit serum level did not differ between asthmatic patients and healthy controls, however the level of sc-kit in non-severe asthmatics was significantly higher as compared to patients with severe asthma and healthy controls. In asthmatic patients (n = 63) the level of sc-kit correlated positively with FEV1% predicted value (R = 0,45; p < 0,001) and MEF25% predicted value (R = 0,33; p < 0,01). The level of sc-kit inversely correlated with the dose of inhaled glucocorticosteroids taken by the patients (R = -0,26; p < 0,01). Conclusion Serum levels of SCF and its soluble receptor c-kit seem to be reflect asthma severity suggesting a role for these molecules in asthmatic inflammation.

Introduction: War in Ukraine prompted an enormous refugee influx into Europe, including approximately 4200 people with HIV. The unique healthcare features of Ukrainian refugees living with HIV were compared between two infectious disease departments in Bonn, Germany, and Szczecin, Poland. Methods: This is a retrospective study on 161 people living with HIV (PLWH) refugees from Ukraine seeking care in Bonn (n = 30) and Szczecin (n = 131) between April 2022 and May 2023. Demographic, virologic, immunologic, and coinfection data were analyzed. Results: The majority of the studied individuals were female: 64% (n = 84) in Szczecin and 60% (n = 18) in Bonn. The main HIV transmission mode was heterosexual sex in 73.5% (n = 114). All were on combined antiretroviral therapy (cART) on arrival, primarily on the TLD regimen (TDF/3TC/DTG) (68.4%, n = 106). In Germany, cART was most frequently switched to BIC/TAF/FTC in 83.4% (n = 25); in Poland, the most common combination was TDF/FTC + DTG (58%, n = 76). A prevalence of replicating hepatitis C was in 11.7% (n = 15), and that for chronic hepatitis B (HBV) was in 4.7% (n = 4). History of past tuberculosis was reported in 16.9% (n = 14, Poland, and n = 7, Germany). Follow-up after 6 months showed immunological reconstitution with a mean increase of CD4+ of 10 (IQR: -69.5-120.5) cells/µL in Poland and 51.5 (IQR: -22.5-135.5) cells/µL in Germany; p = 0.04. Virologic suppression (<40 HIV-RNA/mL) was high in care entry (n = 62; 98%) for Poland, and n = 26 (92.6%) for Germany, and suppression was achieved in the majority of patients in the 6-month control (89.7% in Poland vs. 95.7% in Germany). Conclusions: Health challenges posed by war migration extend beyond HIV to coinfections as HBV, HCV, and tuberculosis give an indication for a broader search for coinfections, often less common in the new country.

Background and Purpose: Neuroblastoma 4S is a rare subtype of metastatic neuroblastoma found in children younger than 12 months, characterized by liver, skin, or bone marrow metastases. While the prognosis for patients is generally favorable, rapid progression of liver metastases can lead to life-threatening organ insufficiency. In such cases, immediate treatment with chemotherapy or radiotherapy is necessary. Given the recent decline in radiotherapy utilization, this study aims to reassess its role, evaluating its effectiveness and toxicity., Materials and Methods: We conducted a systematic review and an institutional retrospective analysis to assess the use of radiotherapy for hepatomegaly in patients with neuroblastoma 4S. The study included data from 164 patients from the literature and 16 patients from our institutional cohort. We extracted and analyzed data on short- and long-term outcomes, as well as reports of radiotherapy-induced toxicity., Results: Our institutional data showed that 81 % of patients responded to low-dose radiotherapy administered at a median dose of 450 cGy in three fractions, resulting in liver shrinkage and symptom resolution. Based on the systematic review, 1-year survival rate was 80 %, while 5-year survival rate was 75 %. No serious toxicity was observed with the current low-dose radiotherapy; however, one case of induced secondary malignancy was reported., Conclusion: Radiation therapy is an effective treatment modality for hepatomegaly in patients with neuroblastoma 4S, with a success rate of about 80 %. Despite being administered to infants, a low dose of 450-600 cGy does not result in toxicity related to the kidneys, liver, or posture defects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

This study presents the functionalization of silk fabric with SWCNT ink. The first step was the formation of a polydopamine (PDA) thin coating on the silk fabric to allow for effective bonding of SWCNTs. PDA formation was carried out directly on the fabric by means of polymerization of dopamine in alkali conditions. The Silk/PDA fabric was functionalized with SWCNT ink of different SWCNT concentrations by using the dip-coating method. IR and Raman analyses show that the dominant β-sheet structure of silk fibroin after the functionalization process remains unchanged. The heat resistance is even slightly improved. The hydrophobic silk fabric becomes hydrophilic after functionalization due to the influence of PDA and the surfactant in SWCNT ink. The ink significantly changes the electrical properties of the silk fabric, from insulating to conductive. The volume resistance changes by nine orders of magnitude, from 2.4 × 10 12 Ω to 2.3 × 10 3 Ω for 0.12 wt.% of SWCNTs. The surface resistance changes by seven orders of magnitude, from 2.1 × 10 12 Ω to 2.4 × 10 5 Ω for 0.17 wt.% of SWCNTs. The volume and surface resistance thresholds are determined to be about 0.05 wt.% and 0.06 wt.%, respectively. The low value of the percolation threshold indicates efficient functionalization, with high-quality ink facilitating the formation of percolation paths through SWCNTs and the influence of the PDA linker.

Nowadays, an efficient and robust virtual screening procedure is crucial in the drug discovery process, especially when performed on large and chemically diverse databases. Virtual screening methods, like molecular docking and classic QSAR models, are limited in their ability to handle vast numbers of compounds and to learn from scarce data, respectively. In this study, we introduce a universal methodology that uses a machine learning-based approach to predict docking scores without the need for time-consuming molecular docking procedures. The developed protocol yielded 1000 times faster binding energy predictions than classical docking-based screening. The proposed predictive model learns from docking results, allowing users to choose their preferred docking software without relying on insufficient and incoherent experimental activity data. The methodology described employs multiple types of molecular fingerprints and descriptors to construct an ensemble model that further reduces prediction errors and is capable of delivering highly precise docking score values for monoamine oxidase ligands, enabling faster identification of promising compounds. An extensive pharmacophore-constrained screening of the ZINC database resulted in a selection of 24 compounds that were synthesized and evaluated for their biological activity. A preliminary screen discovered weak inhibitors of MAO-A with a percentage efficiency index close to a known drug at the lowest tested concentration. The approach presented here can be successfully applied to other biological targets as target-specific knowledge is not incorporated at the screening phase., (© 2024. The Author(s).)

The in vivo effectiveness of DNAzymes 10-23 (Dz10-23) is limited due to the low concentration of divalent cations. Modifications of the catalytic loop are being sought to increase the activity of Dz10-23 in physiological conditions. We investigated the effect of 5'S or 5'R 5',8-cyclo-2'deoxyadenosine (cdA) on the activity of Dz10-23. The activity of Dz10-23 was measured in a cleavage assay using radiolabeled RNA. The Density Functional Tight Binding methodology with the self-consistent redistribution of Mulliken charge modification was used to explain different activities of DNAzymes. The substitution of 2'-deoxyadenosine with cdA in the catalytic loop decreased the activity of DNAzymes. Inhibition was dependent on the position of cdA and its absolute configuration. The order of activity of DNAzymes was as follows: wt-Dz > S cdA5-Dz ≈ R cdA15-Dz ≈ S cdA15-Dz > R cdA5-Dz. Theoretical studies revealed that the distance between phosphate groups at position 5 in R cdA5-Dz was significantly increased compared to wt-Dz, while the distance between O4 of dT4 and nonbonding oxygen of PO 2 attached to 3'O of dG2 was much shorter. The strong inhibitory effect of RcdA5 may result from hampering the flexibility of the catalytic loop (increased rigidity), which is required for the proper positioning of Me 2+ and optimal activity., Competing Interests: The authors declare no conflicts of interest.

Vitamin B12 plays a key role in DNA stability. Research indicates that vitamin B12 deficiency leads to indirect DNA damage, and vitamin B12 supplementation may reverse this effect. Vitamin B12 acts as a cofactor for enzymes such as methionine synthase and methylmalonyl-CoA mutase, which are involved in DNA methylation and nucleotide synthesis. These processes are essential for DNA replication and transcription, and any impairment can result in genetic instability. In addition, vitamin B12 has antioxidant properties that help protect DNA from damage caused by reactive oxygen species. This protection is achieved by scavenging free radicals and reducing oxidative stress. In addition to their protective functions, cobalamins can also generate DNA-damaging radicals in vitro that can be useful in scientific research. Research is also being conducted on the use of vitamin B12 in medicine as vectors for xenobiotics. In summary, vitamin B12 is an essential micronutrient that plays a vital role in DNA stability. It acts as a cofactor for enzymes involved in the synthesis of nucleotides, has antioxidant properties and has potential value as a generator of DNA-damaging radicals and drug transporters.

The classical low-molecular-weight drugs are designed to bind with high affinity to the biological targets endowed with receptor or enzymatic activity, and inhibit their function. However, there are many non-receptor or non-enzymatic disease proteins that seem undruggable using the traditional drug approach. This limitation has been overcome by PROTACs, bifunctional molecules that are able to bind the protein of interest and the E3 ubiquitin ligase complex. This interaction results in the ubiquitination of POI and subsequent proteolysis in the cellular proteasome. Out of hundreds of proteins serving as substrate receptors in E3 ubiquitin ligase complexes, current PROTACs recruit only a few of them, including CRBN, cIAP1, VHL or MDM-2. This review will focus on PROTACs recruiting CRBN E3 ubiquitin ligase and targeting various proteins involved in tumorigenesis, such as transcription factors, kinases, cytokines, enzymes, anti-apoptotic proteins and cellular receptors. The structure of several PROTACs, their chemical and pharmacokinetic properties, target affinity and biological activity in vitro and in vivo, will be discussed. We will also highlight cellular mechanisms that may affect the efficacy of PROTACs and pose a challenge for the future development of PROTACs.

The pine-tree lappet moth, D. pini, is a harmful defoliator of pine forests in Europe and Asia and a potentially invasive species in North America. The lures for trapping D. pini males based on two known components of its sex pheromone appeared weakly attractive to male moths. Identification of all components of the sex pheromone might allow for the development of more effective lures. The pheromone was sampled from virgin females using SPME and analyzed using gas chromatography coupled with mass spectrometry. Four new likely components (( Z 5)-dodecenal, ( Z 5)-dodecen-1-ol, ( Z 5)-decen-1-yl acetate, ( Z 5)-tetradecen-1-yl acetate) and two known components (( Z 5, E 7)-dodecadienal, ( Z 5, E 7)-dodecadien-1-ol) were identified based on comparison against authentic standards, Kováts indices and spectra libraries. The samples also contained several sesquiterpenes. Wind tunnel and field experiments showed that some blends of synthetic pheromone components alone or enriched with Scots pine essential oil ( SPEO ) were attractive to D. pini males. One component-( Z 5)-decen-1-yl acetate-had a repelling effect. The presented knowledge of D. pini sex pheromone provides a basis for developing optimal lures for monitoring or controlling insect populations.

Objectives: Possible immunomodulatory effect of amantadine in patients treated in intensive care unit (ICU), mostly among patients with brain injuries or vascular diseases was observed in several studies. The potential antiviral effect of amantadine against SARS-CoV-2 was discarded in clinical trials; however, immunomodulatory potential was not studied. The aim of the study was to investigate the effect of immunomodulatory amantadine therapy on mortality in patients with respiratory insufficiency due to COVID-19 requiring mechanical ventilation in ICU., Methods: Retrospective analysis of 241 cases of 141 (58.5%) receiving intravenous amantadine sulfate vs 100 (41.5%) controls on standard of care only was performed., Results: Overall mortality was 72.6%, being notably lower among amantadine treated patients (59.5%, n = 84) compared with controls (91%, n = 91), P-value = 0.001. In multivariate models administration of amantadine was independently associated with lower mortality rate (hazard ratio: 0.220, CI: 0.146-0.333 P-value = 0.001). Furthermore, survival was improved in patients who received amantadine; late administration of amantadine after 5th day was independently associated with lower mortality (hazard ratio: 0.560, CI: 0.313-0.999, P-value = 0.050)., Conclusion: In patients treated in ICU with severe respiratory failure, administration of amantadine is associated with lower mortality, which may be associated with the potential anti-inflammatory and immunomodulatory effects of this agent., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive primary malignancy of the pancreas, with a dismal prognosis and limited treatment options. It possesses a unique tumor microenvironment (TME), generating dense stroma with complex elements cross-talking with each other to promote tumor growth and progression. Diversified neural components makes for not having a full understanding of their influence on its aggressive behavior. The aim of the study was to summarize and integrate the role of nerves in the pancreatic tumor microenvironment. The role of autonomic nerve fibers on PDAC development has been recently studied, which resulted in considering the targeting of sympathetic and parasympathetic pathways as a novel treatment opportunity. Perineural invasion (PNI) is commonly found in PDAC. As the severity of the PNI correlates with a poorer prognosis, new quantification of this phenomenon, distinguishing between perineural and endoneural invasion, could feature in routine pathological examination. The concepts of cancer-related neurogenesis and axonogenesis in PDAC are understudied; so, further research in this field may be warranted. A better understanding of the interdependence between the neural component and cancer cells in the PDAC microenvironment could bring new nerve-oriented treatment options into clinical practice and improve outcomes in patients with pancreatic cancer. In this review, we aim to summarize and integrate the current state of knowledge and future challenges concerning nerve-cancer interactions in PDAC.

Textile structures with various bioactive and functional properties are used in many areas of medicine, special clothing, interior textiles, technical goods, etc. We investigated the effect of two different textile woven structures made of 90% polyester with 10% polyamide (PET) and 100% cotton (CO) modified by magnetron sputtering with copper (Cu) on bioactive properties against Gram-positive and Gram-negative bacteria and four viruses and also on the some comfort parameters. PET/Cu and CO/Cu fabrics have strong antibacterial activity against Staphylococcus aureus and Klebsiella pneumonia . CO/Cu fabric has good antiviral activity in relation to vaccinia virus (VACV), herpes simplex virus type 1 (HSV-1) and influenza A virus H1N1 (IFV), while its antiviral activity against mouse coronavirus (MHV) is weak. PET/Cu fabric showed weak antiviral activity against HSV-1 and MHV. Both modified fabrics showed no significant toxicity in comparison to the control medium and pristine fabrics. After Cu sputtering, fabric surfaces became hydrophobic and the value of the surface free energy was over four times lower than for pristine fabrics. The modification improved thermal conductivity and thermal diffusivity, facilitated water vapour transport, and air permeability did not decrease.

This study's aim was assessing of the relationship between mentalization and life satisfaction and the level of adaptation to oncological disease in patients with breast cancer. The study involved 41 women ( M = 59.88; SD = 8.81) with breast cancer who completed their treatments and participated in a cancer rehabilitation program. In the study, we used the Mentalization Questionnaire (MZQ), the Satisfaction Life Scale (SWLS), and the Mini-Mental Adjustment to Cancer Scale (Mini-MAC). The mean of declared level of mentalization was 45.54 ( SD = 11.65). The significant correlation between mentalization (its general value and individual dimensions) and satisfaction with life/mental adjustment to cancer was observed. The strongest positive correlations were noted between refusing self-reflection, helplessness-hopelessness, and anxious preoccupation and the negative correlation between mentalization and satisfaction with life. Mentalization was a predictor of satisfaction with life and mental adjustment to illness. Mentalization was related with life satisfaction and adjustment to cancer in patients with breast cancer, which is in line with previous studies suggesting the crucial role of subjective psychological factors in maintaining mental health.

The search is ongoing for new anticancer therapeutics that would overcome resistance to chemotherapy. This includes chronic myeloid leukemia, particularly suitable for the studies of novel anticancer compounds due to its homogenous and well-known genetic background. Here we show anticancer efficacy of novel dicarboximide denoted BK124.1 (C 31 H 37 ClN 2 O 4 ) in a mouse CML xenograft model and in vitro in two types of chemoresistant CML cells: MDR1 blasts and in CD34 + patients' stem cells (N = 8) using immunoblotting and flow cytometry. Intraperitoneal administration of BK124.1 showed anti-CML efficacy in the xenograft mouse model (N = 6) comparable to the commonly used imatinib and hydroxyurea. In K562 blasts, BK124.1 decreased the protein levels of BCR-ABL1 kinase and its downstream effectors, resulting in G2/M cell cycle arrest and apoptosis associated with FOXO3a/p21 waf1/cip1 upregulation in the nucleus. Additionally, BK124.1 evoked massive apoptosis in multidrug resistant K562-MDR1 cells (IC 50 = 2.16 μM), in CD34 + cells from CML patients (IC 50 = 1.5 µM), and in the CD34 + /CD38 - subpopulation consisting of rare, drug-resistant cancer initiating stem cells. Given the advantages of BK124.1 as a potential chemotherapeutic and its unique ability to overcome BCR-ABL1 dependent and independent multidrug resistance mechanisms, future development of BK124.1 could offer a cure for CML and other cancers resistant to present drugs.

The aim of the research was to evaluate the changes in the surface properties of five functional clothing materials with water-repellent finishes (including PFC-free finish) after 1, 5, and 10 washes with three detergents. A new approach to the interpretation of the water-repellent properties of textile materials is presented, based on two techniques, i.e., the spray test method and contact angle measurements. The results showed that washing materials with hydrophobic finishes can cause significant changes in their properties, which are mainly dependent on the composition and structure of the material, as well as the type of hydrophobic finish. The PFC-free finish is the least resistant to washing. For all materials with PFC finishes, the water repellency depends on the fluorine content on the surface and fabric topography. It was also found that increasing washing frequency resulted in a gradual decrease in water repellency. The loss of water repellency below an acceptable level (Grade 3) occurred after the fifth washing for all materials. Significant differences in the interpretation of the results of the spray test and contact angle measurements were observed. Using these methods separately provides information on the changes in the surface properties of the tested materials; however, their parallel application allows for obtaining complementary data, which is important for the proper interpretation of results.

New functionalization methods of meta - and para -aramid fabrics with silver nanowires (AgNWs) and two silanes (3-aminopropyltriethoxysilane (APTES)) and diethoxydimethylsilane (DEDMS) were developed: a one-step method (mixture) with AgNWs dispersed in the silane mixture and a two-step method (layer-by-layer) in which the silanes mixture was applied to the previously deposited AgNWs layer. The fabrics were pre-treated in a low-pressure air radio frequency (RF) plasma and subsequently coated with polydopamine. The modified fabrics acquired hydrophobic properties (contact angle Θ W of 112-125°). The surface free energy for both modified fabrics was approximately 29 mJ/m 2 , while for reference, meta - and para -aramid fabrics have a free energy of 53 mJ/m 2 and 40 mJ/m 2 , respectively. The electrical surface resistance (R s ) was on the order of 10 2 Ω and 10 4 Ω for the two-step and one-step method, respectively. The electrical volume resistance (R v ) for both modified fabrics was on the order of 10 2 Ω. After UV irradiation, the Rs did not change for the two-step method, and for the one-step method, it increased to the order of 10 10 Ω. The specific strength values were higher by 71% and 63% for the meta -aramid fabric and by 102% and 110% for the para -aramid fabric for the two-step and one-step method, respectively, compared to the unmodified fabrics after UV radiation.

Invasive slugs generate significant problems in the area of horticultural and agricultural production. Despite the multitude of methods to reduce the pest population, including preventive, mechanical, agrotechnical, cultivation, biological, and chemical treatments, no effective plant protection strategy has been developed so far. In this paper, a solution based on modified non-woven fabric with bioactive molluscicidal properties using the extract of tansy flower, metaldehyde, and abamectin (Vertigo ® 018 EC) was proposed. All modified mats show significant anti-slug properties in comparison to control, and molluscicidal properties depend on the type of active substance. Non-woven modified with commonly used metaldehyde demonstrated fast action against slugs and presents the highest efficiency. The effectiveness of non-woven mats with Vertigo ® 018 EC is lower than for the mats with metaldehyde but higher than for the mats modified with tansy flower extract. The proposed solution will enable removing and neutralization of molluscicide from the fields, after the efficient pest control, according to circular economy principles. Moreover, it may allow for better control of the molluscicide release to the environment in comparison to widely used pellets, and contribute to the virtual protection of plants against invasive slugs.

In continuation of our research on the influence of selenium incorporation on the biosynthesis, structure, and immunomodulatory and antioxidant activities of polysaccharides of fungal origin, we have isolated from a post-culture medium of Lentinula edodes a selenium (Se)-containing exopolysaccharide fraction composed mainly of a highly branched 1-6-α-mannoprotein of molecular weight 4.5 × 10 6 Da, with 15% protein component. The structure of this fraction resembled mannoproteins isolated from yeast and other mushroom cultures, but it was characterized by a significantly higher molecular weight. X-ray absorption fine structure spectral analysis in the near edge region (XANES) suggested that selenium in the Se-exopolysaccharide structure was present mainly at the IV oxidation state. The simulation analysis in the EXAFS region suggested the presence of two oxygen atoms in the region surrounding the selenium. On the grounds of our previous studies, we hypothesized that selenium-enriched exopolysaccharides would possess higher biological activity than the non-Se-enriched reference fraction. To perform structure-activity studies, we conducted the same tests of biological activity as for previously obtained mycelial Se-polyglucans. The Se-enriched exopolysaccharide fraction significantly enhanced cell viability when incubated with normal (human umbilical vein endothelial cells (HUVEC)) cells (but this effect was absent for malignant human cervical HeLa cells) and this fraction also protected the cells from oxidative stress conditions. The results of tests on the proliferation of human peripheral blood mononuclear cells suggested a selective immunosuppressive activity, like previously tested Se-polyglucans isolated from L. edodes mycelium. The Se-exopolysaccharide fraction, in concentrations of 10-100 µg/mL, inhibited human T lymphocyte proliferation induced by mitogens, without significant effects on B lymphocytes. As with previously obtained Se-polyglucans, in the currently tested Se-polymannans, the selenium content increased the biological activity. However, the activity of selenium exopolysaccharides in all tests was significantly lower than that of previously tested mycelial isolates, most likely due to a different mode of selenium binding and its higher degree of oxidation.

Silk, as a protein fiber characterized by high biocompatibility, biodegradability, and low toxicity, is mainly used as textile structures for various purposes, including for biological applications. The key issue for unlimited silk applicability as a modifier is to prepare its relevant form to cover or introduce to other materials. This study presents silk powder fabrication from Bombyx mori cocoons and non-dyed silk woven fabric through cryogenic milling. The cocoons were milled before and after the degumming process to obtain powders from raw structures and pure fibroin. The powder morphology and composition were analyzed using scanning electron microscopy and energy dispersive spectroscopy. The influence of the milling on the silk structure was studied using infrared and Raman spectroscopies, indicating that silk powders retained dominant β-sheet structure. The powders were also analyzed by differential scanning calorimetry and thermogravimetric techniques. The thermal endothermic peak and onset temperature characteristic for silk decomposition shifted to the lower values for all powders, indicating less thermal stability. However, the process was found to be an efficient way to obtain silk powders. The new milled form of silk can allow its introduction into different matrices or form coatings without using any harsh solvents, enriching them with new features and make more biologically friendly.

This paper presents the characterization of cotton and wool fabrics modified by silver nanowires (AgNWs). The effect of reactive dyeing of wool and cotton fabrics on their modification with AgNWs was analyzed. Both fabrics were dyed using reactive dyes (yellow, red, blue) at four color intensities (0.5, 1, 2, and 5%). Dyed fabrics were characterized by the determined Kubelka-Munk's coefficient ( K / S ) ratio and vibrational spectra (Fourier transform infrared (FTIR) and Raman). Analysis of the amount of AgNWs applied on cotton and wool fabrics indicates that the presence of dye affects the surface modification with AgNWs depending on the type of fibers. While for cotton no significant differences were noted in relation to the color intensity, in the case of wool, the higher the dye contents, the more nanowires were deposited on the surface. Surface-enhanced Raman spectroscopy (SERS) effect accompanying AgNW modification was also observed on wool, similar to the previous study on cotton., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

(1) Background: There is a continuing discussion concerning the impact of preterm birth on Maternal-Infant bonding with inconsistent results. The large burden of preterm births calls for research to evaluate the impact of it on material psychological outcome in the early postpartum period. Thus, the aim of this study was to evaluate the relationship between maternal postpartum bonding with maternal mental health, socio-demographical factors, and child's characteristics. (2) Methods: A cross-sectional study design was used. In total, 72 women (a mean age of 31.44 years old) of preterm infants (mean gestational age = 33.54; range 24-36) filled out socio-demographic questionnaires, Postpartum Bonding Questionnaire (PBQ), Edinburgh Postpartum Depression Scale (EPDS), Postpartum Depression Screening Scale (PDSS), Generalized Anxiety Disorder Assessment (GAD-7), and Parental Stress Scale (PSS) 1-3 days post-delivery; (3) Results: The results analyses have shown positive correlations between the overall result of maternal postpartum bonding with stress ( p < 0.01), maternal educational level ( p < 0.01), maternal age ( p < 0.05) and the number of children ( p < 0.01). However, there were no significant relationships between other investigated variables. The results of linear regression have revelated the important role of the overall scores in experience of stress among mothers (explaining 49% of the variability). The mediating role of maternal stress on maternal postpartum bonding was not found. That relationship of maternal postpartum bonding and maternal stress was not moderated through socio-demographic variables. (4) Conclusions: In this study mothers of prematurely born children had a good level of Maternal-Infant bonding. Maternal stress was found to be a predictor of maternal postpartum bonding among the tested variables. Surprisingly, the study results did not show significant relationships between maternal postpartum bonding and maternal mental health (depression and anxiety).

The purpose of this study was to examine the severity of post-traumatic stress disorder (PTSD) symptoms related to the COVID-19 pandemic in people with no diagnosis of mental illness, as well as in people who were diagnosed with depression or anxiety. Moreover, this study aimed to investigate the interplay between PTSD symptoms and self-assessed mental health associated with well-being. The 210 participants were divided into 3 groups: mentally healthy, participants with diagnosed depression, and participants with anxiety disorders. To evaluate the subjective well-being of the participants, the Polish adaptation of the Mental Health Continuum-Short Form (MHC-SF) was applied. The Impact Event Scale-Revised (IES-R) was used to measure the severity of PTSD symptoms. At least a moderate worsening of PTSD symptoms was observed in participants of all groups. The results were as follows: healthy participants M = 37.35 ( SD = 18.46); participants with depression M = 36.05 ( SD = 18.02); participants with anxiety M = 44.52 ( SD = 18.08). The participants diagnosed with depression showed the lowest level of mental well-being M = 41.58 ( SD = 15.02). Conclusion: People diagnosed with depression had both the lowest level of well-being and the lowest severity of symptoms specific to PTSD. In all three groups, lower emotional well-being was linked to greater PTSD symptoms.

This study was aimed towards the development of a novel microfluidic approach for the preparation of (co)polymeric and hybrid nanoparticles (NPs) composed of (co)polymers/tannic acid (TA) in the microfluidic flow-focusing glass-capillary device. The MiliQ water was used as water phase, whereas the organic phase was composed of poly(ε-caprolactone) (PCL) and poly(trimethylene carbonate) (PTMC) homopolymers and (co)polymers with different proportion of comonomers which were prepared via enzymatic polymerization that allows avoiding the usage of potentially toxic catalyst. To prepare hybrid NPs, TA was additionally added to the organic phase. Subsequently, as a result of mixing between these distinct phases in microfluidic channels, the nanoprecipitation in the form of spherical NPs occurs. The size of NPs was tuned over the range of 140-230 nm by controlling phase flow rates and the composition of NPs. Moreover, the release studies of the encapsulated anticancer drug doxorubicin (DOX) demonstrated that the drug release is greatly influenced by the (co)polymers composition, their molecular weight, NPs size, and the presence of TA. The antitumor activities of the (co)polymeric and hybrid NPs toward breast cancer cells (MCF-7) were tested in vitro. Among all tested formulation, the NPs composed of PCL/TA most efficiently inhibit the cell proliferation of MCF-7 cells, most importantly, their efficiency was higher than free DOX. The proposed strategy may provide an efficient alternative for the construction of nanocarriers with great potential in anticancer therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Based on previously identified dicarboximides with significant anticancer and immunomodulatory activities, a series of 26 new derivatives were designed and synthesized by the Diels-Alder reaction between appropriate diene and maleimide or hydroxymaleimide moieties. The resulting imides were functionalized with alkanolamine or alkylamine side chains and subsequently converted to their hydrochlorides. The structures of the obtained compounds were confirmed by 1H and 13C NMR and by ESI MS spectral analysis. Their cytotoxicity was evaluated in human leukemia (K562, MOLT4), cervical cancer (HeLa), and normal endothelial cells (HUVEC). The majority of derivatives exhibited high to moderate cytotoxicity and induced apoptosis in K562 cells. Microarray gene profiling demonstrated upregulation of proapoptotic genes involved in receptor-mediated and mitochondrial cell death pathways as well as antiapoptotic genes involved in NF-kB signaling. Selected dicarboximides activated JNK and p38 kinases in leukemia cells, suggesting that MAPKs may be involved in the regulation of apoptosis. The tested dicarboximides bind to DNA as assessed by a plasmid DNA cleavage protection assay. The selected dicarboximides offer new scaffolds for further development as anticancer drugs.

Liver injury-expressed as elevated liver enzymes-is common in patients with COVID-19. Little is known about the potential mechanisms of liver damage by SARS-CoV-2. A direct cytopathic effect on hepatocytes as well as injury related to hypoxia or hepatotoxicity are being considered. The aim of the study was to compare the clinical characteristic of COVID-19 disease in patients with normal and abnormal liver enzymes activity. A group of 150 patients with COVID-19, hospitalized in our center, was analyzed. Patients with the known liver comorbidities were excluded ( n = 15). Clinical features and laboratory parameters were compared between patients with normal and abnormal aminotransferase values. Liver injury expressed as any alanine aminotransferase (ALT) elevation was noted in 45.6% of patients hospitalized due to COVID-19. The frequencies of aspartate aminotransferase (AST) elevation were lower. It was noted that elevated ALT/AST unfavorably affected other parameters related to liver function such as albumin level; gamma-glutamyl transpeptidase (GGTP); and partly, ALP activity and influenced inflammation-related parameters. The most probable cause of mild hepatitis during COVID-19 was anoxia and immune-mediated damage due to the inflammatory response following SARS-CoV-2 infection. A direct cytopathic effect of SARS-CoV-2 on hepatocytes, albeit less probable, can be considered as well. The use of potentially hepatotoxic drugs may contribute to liver damage.

Since silver nanowires (AgNWs) show high infrared reflectance many studies present their applicability as thermal management products for various wearable textiles. However, their use for practical purposes is only partially evaluated, without focusing on improving their low atmospheric and liquid stability. This report describes a new approach for the topic and proposes a facile method of Ag nanowire passivation with a SnO 2 layer for high environmental stability and retention of high infrared reflectance. The one-step passivation process of AgNWs was carried out in the presence of sodium stannate in an aqueous solution at 100 °C, and resulted in the formation of core/shell Ag/SnO 2 nanowires. This study presents the morphological, chemical, and structural properties of Ag/SnO 2 NWs formed with a 14 nm thick SnO 2 shell, consisting of 7 nm rutile-type crystals, covering the silver metallic core. The optical properties of the AgNWs changed significantly after shell formation, and the longitudinal and transverse modes in the surface plasmon resonance spectrum were red shifted as a result of the surrounding media dielectric constant changes. The passivation process protected the AgNWs from decomposition in air for over 4 months, and from dissolution in a KCN solution at concentrations up to 0.1 wt%. Moreover, the report shows the microwave irradiation effect on the shell synthesis and previously synthesised Ag/SnO 2 NWs. The post-synthesis irradiation, as well as the SnO 2 shell obtained by microwave assistance, did not allow long-term stability to be achieved. The microwave-assisted synthesis process was also not fast enough to inhibit the formation of prismatic silver structures from the nanowires. The Ag/SnO 2 NWs with a shell obtained by a simple hydrolysis process, apart from showing high infra-red reflectance on the para -aramid fabric, are highly environmentally stable. The presented SnO 2 shell preparation method can protect the AgNW's surface from dissolution or decomposition and facilitate the designing of durable smart wearable thermal materials for various conditions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

(1) Background: Natural peptides supporting the innate immune system studied at the functional and mechanistic level are a rich source of innovative compounds for application in human therapy. Increasing evidence indicates that apart from antimicrobial activity, some of them exhibit selective cytotoxicity towards tumor cells. Their cationic, amphipathic structure enables interactions with the negatively-charged membranes of microbial or malignant cells. It can be modeled in 3D by application of dendrimer chemistry. (2) Methods: Here we presented design principles, synthesis and bioactivity of branched peptides constructed from ornithine (Orn) assembled as proline (Pro)- or histidine (His)-rich dendrons and dendrimers of the bola structure. The impact of the structure and amphipathic properties of dendrons/dendrimers on two glioblastoma cell lines U87 and T98G was studied with the application of proliferation, apoptosis and cell migration assays. Cell morphology/cytoskeleton architecture was visualized by immunofluorescence microscopy. (3) Results: Dimerization of dendrons into bola dendrimers enhanced their bioactivity. Pro- and His-functionalized bola dendrimers displayed cytostatic activity, even though differences in the responsiveness of U87 and T98G cells to these compounds indicate that their bioactivity depends not only on multiple positive charge and amphipathic structure but also on cellular phenotype. (4) Conclusion: Ornithine dendrons/dendrimers represent a group of promising anti-tumor agents and the potential tools to study interrelations between drug bioactivity, its chemical properties and tumor cells' phenotype.

The acceptance of disability is recognized as one of the most frequently mentioned factors that plays a particularly significant role in subjective well-being. However, so far, only a very small amount of research has been undertaken to clarify how and why acceptance of illness relates to eudemonic well-being. Hence, comprehension of the direct and indirect effects underlying this relationship seems essential for interventions that increase the recovery of people with impairments and enhance their quality of life. The current research was aimed at investigating the association between acceptance of illness, meaning in life, and eudemonic well-being, as well as the possible mediatory effect of meaning in life on the relationship between acceptance of illness and well-being. The sample consisted of 102 participants (71% women) aged between 20 and 64 years. The respondents had a range of different impairments (e.g., cerebral palsy, neurological disorders, spinal muscular atrophy, and sight defects). The Acceptance of Illness Scale, the Meaning in Life Questionnaire, and the Ryff Scales of Psychological Well-Being were used. It was confirmed that acceptance of illness correlated positively and significantly with the presence of meaning, self-acceptance, positive relations, environmental mastery, personal growth, general well-being, cohesion, flexibility, communication, and family satisfaction. The presence of meaning mediated the relationship between acceptance of illness and general well-being with its four other dimensions: self-acceptance, environmental mastery, purpose in life, and personal growth. Conversely, the search for meaning did not have any mediatory effect on this relationship., (Copyright © 2020 Szcześniak, Świątek, Cieślak and Świdurska.)

The aim of the study was to modify the surface free energy (SFE) of meta- (mAr) and para-aramid (pAr) yarns by their activation in low-pressure air radio frequency (RF) (40 kHz) plasma and assessment of its impact on the properties of the yarns. After 10 and 90 min of activation, the SFE value increased, respectively, by 14% and 37% for mAr, and by 10% and 37% for pAr. The value of the polar component increased, respectively by 22% and 57% for mAr and 20% and 62% for pAr. The value of the dispersion component for mAr and pAr increased respectively by 9% and 25%. The weight loss decreased from 49% to 46% for mAr and 62% to 50% for pAr after 90 min of activation. After 90 min, the specific strength for mAr did not change and for pAr it decreased by 40%. For both yarns, the 10 min activation in plasma is sufficient to prepare their surface for planned nanomodification.

A large body of literature indicates that there is a relationship between maternal psychological well-being and the early maternal-infant bond. However, this relationship is not fully understood, due to the different theoretical frameworks of maternal-infant bonding and different data collections points. Thus, the aim of this study was to examine the relationship between the maternal bond and the maternal psychological state including anxiety, stress, and maternal depressive symptoms. In this cohort study, 150 women who gave birth after 37 weeks of pregnancy completed the following self-reports 1-3 days post-delivery: Socio-demographic questionnaire, Postpartum Bonding Questionnaire (PBQ), Edinburgh Postpartum Depression Scale (EPDS), Postpartum Depression Screening Scale (PDSS), Generalized Anxiety Disorder Assessment (GAD-7), and Parental Stress Scale (PSS). The obtained results showed that the maternal level of stress, anxiety and postnatal depressive symptoms are significantly correlated with the maternal-infant bond in Polish mothers. In addition, regression analysis shows that postpartum depressive symptoms and maternal stress are significantly associated with the maternal-infant bonding process in the early postpartum period. This finding emphasizes the importance of identifying maternal mental state difficulties in the early postpartum period in order to provide interventions to help build healthy maternal-infant bonding.

A series of 3-benzylidenechrmanones 1 , 3 , 5 , 7 , 9 and their spiropyrazoline analogues 2 , 4 , 6 , 8 , 10 were synthesized. X-ray analysis confirms that compounds 2 and 8 crystallize in a monoclinic system in P2 1 /n space groups with one and three molecules in each asymmetric unit. The crystal lattice of the analyzed compounds is enhanced by hydrogen bonds. The primary aim of the study was to evaluate the anti-proliferative potential of 3-benzylidenechromanones and their spiropyrazoline analogues towards four cancer cell lines. Our results indicate that parent compounds 1 and 9 with a phenyl ring at C2 have lower cytotoxic activity against cancer cell lines than their spiropyrazolines analogues. Analysis of IC 50 values showed that the compounds 3 and 7 exhibited higher cytotoxic activity against cancer cells, being more active than the reference compound (4-chromanone or quercetin). The results of this study indicate that the incorporation of a pyrazoline ring into the 3-arylideneflavanone results in an improvement of the compounds' activity and therefore it may be of use in the search of new anticancer agents. Further analysis allowed us to demonstrate the compounds to have a strong inhibitory effect on the cell cycle. For instance, compounds 2 , 10 induced 60% of HL-60 cells to be arrested in G2/M phase. Using a DNA-cleavage protection assay we also demonstrated that tested compounds interact with DNA. All compounds at the concentrations corresponding to cytotoxic properties are not toxic towards red blood cells, and do not contribute to hemolysis of RBCs.

Spirituality and satisfaction with life are psychological factors related to health behavior. The aim of the study was to determine whether satisfaction with life acts as a mediator in the relationship between the spirituality of residents of long-term care institutions and their health-related behavior. A total of 102 people aged 60-99 were examined. It was found that satisfaction with life played a mediating role in the relationship between spirituality and health behavior. The study addresses the gap in knowledge regarding institutionalized older adults, exploring the role of spirituality and satisfaction with life on lifestyle in nursing home settings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of the study was the combination of two measurement methods, the differential scanning calorimetry (DSC) and infrared thermography to evaluate thermal performance of woven and knitted fabrics coated with acrylic pastes containing 20% (P/20) and 40% (P/40) of microcapsules of phase change materials (MPCM) with transition temperatures of 28 °C (MPCM28) and 43 °C (MPCM43). The DSC analysis showed that the phase transition processes for materials modified with pastes P/20 occur in a narrower temperature range than those modified with P/40 pastes. The initial temperatures T Onset (S-S) and T Onset (S-L) are higher for materials modified respectively with pastes P/20 and P/40. The melting and crystallization enthalpy values of both P/20 coated materials are lower by about 45% and 35% compared to P/40. Infrared thermography analysis showed that materials modified with P/20 are heating up faster than modified with P/40 for both MPCM. In the cooling process for modified fabrics the highest temperature decrease was observed in the first 30s. Materials modified with paste P/40 were cooled more slowly in comparison with paste P/20, both for MPCM28 and MPCM43.

Silver is one of the most toxic heavy metals for plants, inducing various toxic symptoms and metabolic changes. Here, the impact of Ag(I) on Carlina acaulis physiology and selected metabolites was studied using two Ag concentrations (1 or 10 µM) after 14 days of exposure. The higher concentration of Ag(I) evoked reduction of growth, while 1 µM Ag had a growth-promoting effect on root biomass. The translocation factor (<0.04) showed that Ag was mainly retained in the roots. The 1 µM Ag concentration increased the level of low-molecular-weight organic acids (LMWOAs), while 10 µM Ag depleted these compounds in the roots. The increased concentration of Ag(I) elevated the accumulation of phytochelatins (PCs) in the roots and reduced glutathione (GSH) in the shoots (but not in the roots). At 1 µM, Ag(I) elevated the level of phenolic and triterpene acids, while the 10 µM Ag treatment increased the carlina oxide content in the roots. The obtained results indicate an alteration of metabolic pathways of C. acaulis to cope with different levels of Ag(I) stress. Our data imply that the intracellular binding of Ag(I) and nonenzymatic antioxidants contribute to the protection against low concentrations of Ag ions., Competing Interests: The authors declare no conflict of interest.

We identified novel dicarboximides that were selectively cytotoxic towards human leukemia cells. Using chemical and biological methods, we characterized the biological activity, identified cellular protein targets and defined the mechanism of action of the test dicarboximides. The reported IC 50 values (concentration required to reduce cell survival fraction to 50% of control) of selected dicarboximides were similar or lower than IC 50 of registered anticancer drugs, for example cytarabine, sorafenib, irinotecan. Test compounds induced apoptosis in chronic myelogenous (K562) and acute lymphoblastic (MOLT-4) leukemia cells by activation of receptor and mitochondrial apoptotic pathways and increased the expression of proapoptotic genes ( BAX, NOXA, HTRA2, TNFRSF10B, ESRRBL1) . Selected dicarboximides displayed immunomodulatory activity and downregulated IKZF1 and IKZF3 transcription factors in K562 and MOLT-4 leukemia cells. ATP-binding cassette protein 50 (ABC50) was identified as a target for dicarboximides. Cancer cells with knocked down ABC50 showed increased resistance to dicarboximides. Based on the structure of dicarboximides and thalidomide, novel proteolysis-targeting chimeras (PROTACs) were synthesized and used as tools to downregulate ABC50 in leukemia cells.

The results of our previous research indicated that some derivatives of benzofurans, particularly halogeno-derivatives, are selectively toxic towards human leukemia cells. Continuing our work with this group of compounds we here report new data on the synthesis as well as regarding the physico-chemical and biological characterization of fourteen new derivatives of benzofurans, including six brominated compounds. The structures of all new compounds were established by spectroscopic methods ( 1 H- and, 13 C-NMR, ESI MS), and elemental analyses. Their cytotoxicity was evaluated against K562 (leukemia), MOLT-4 (leukemia), HeLa (cervix carcinoma), and normal cells (HUVEC). Five compounds ( 1c , 1e , 2d , 3a , 3d ) showed significant cytotoxic activity against all tested cell lines and selectivity for cancer cell lines. The SAR analysis (structure-activity relationship analysis) indicated that the presence of bromine introduced to a methyl or acetyl group that was attached to the benzofuran system increased their cytotoxicity both in normal and cancer cells.

Introduction: The present study investigated students' preferences about technology tools and digital education activities to be used in classroom to facilitate the implementation of a mental health promotion program., Method: Students' preferences have been elicited during one session focus group lasting 60 minutes. Overall, 26 focus groups, facilitated by 33 teachers, were organized in 9 schools of five European countries. Overall, 283 students who attended the first, second and third year of middle school (aged 10-15 years) volunteered to participate in the focus groups., Results: The majority of preferences indicated smartphone to communicate or to get information and tablet for a better use in classroom. Collaborative games have been considered as more useful and beneficial compared to the other digital educational activities proposed., Conclusions: Teachers require further insight into the pedagogical role of ICT and training. There is a need to encourage them to provide opportunities to allow students to use technology to solve problems or develop abilities for a better socio-emotional functioning and, ultimately, mental health.