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The 3D reconstruction of simple structured materials using a confocal microscope is widely used in many different areas including civil engineering. Nonetheless, scans of porous materials such as concrete or cement paste are highly problematic. The well-known problem of these scans is low depth resolution in comparison to the horizontal and vertical resolution. The degradation of the image depth resolution is caused by systematic errors and especially by different random events. Our method is focused on the elimination of such random events, mainly the additive noise. We use an averaging method based on the Lindeberg-Lévy theorem that improves the final depth resolution to a level comparable with horizontal and vertical resolution. Moreover, using the least square method, we also precisely determine the limit value of a depth resolution. Therefore, we can continuously evaluate the difference between current resolution and the optimal one. This substantially simplifies the scanning process because the operator can easily determine the required number of scans.

Overexpression of ATP-binding cassette (ABC) transporters in cancer cells results in multidrug resistance (MDR) which leads to unsuccessful chemotherapy. The most important MDR-associated members of ABC superfamily are ABC B1/P-glycoprotein/MDR1, ABC C1/multidrug resistance associated protein 1 (MRP1), and ABC G2/BCRP. This study is not only focused on function, substrates, and localization of these popular proteins but also on other ABC C family members such as ABC C2–6/MRP2-6 and ABC C7/CFTR. Current research is mainly oriented on the cancer-promoting role of these proteins, but important lessons could also be learned from the physiological roles of these proteins or from polymorphisms affecting their function. Thorough knowledge of structure and detailed mechanism of efflux can aid in the discovery of new chemotherapy targets in the future. Although the best way on how to deal with MDR would be to prevent its development, we describe some new promising strategies on how to conquer both inherited and induced MDRs.

Abstract Background Lupulin glands of hop produce a specific metabolome including hop bitter acids valuable for the brewing process and prenylflavonoids with promising health-beneficial activities. The detailed analysis of the transcription factor (TF)-mediated regulation of the oligofamily of one of the key enzymes, i.e., chalcone synthase CHS_H1 that efficiently catalyzes the production of naringenin chalcone, a direct precursor of prenylflavonoids in hop, constitutes an important part of the dissection of the biosynthetic pathways leading to the accumulation of these compounds. Results Homologues of flavonoid-regulating TFs HlMyb2 (M2), HlbHLH2 (B2) and HlWDR1 (W1) from hop were cloned using a lupulin gland-specific cDNA library from the hop variety Osvald's 72. Using a "combinatorial" transient GUS expression system it was shown that these unique lupulin-gland-associated TFs significantly activated the promoter (P) of chs_H1 in ternary combinations of B2, W1 and either M2 or the previously characterized HlMyb3 (M3). The promoter activation was strongly dependent on the Myb-P binding box TCCTACC having a core sequence CCWACC positioned on its 5' end region and it seems that the complexity of the promoter plays an important role. M2B2W1-mediated activation significantly exceeded the strength of expression of native chs_H1 gene driven by the 35S promoter of CaMV, while M3B2W1 resulted in 30% of the 35S:chs_H1 expression level, as quantified by real-time PCR. Another newly cloned hop TF, HlMyb7, containing a transcriptional repressor-like motif pdLNLD/ELxiG/S (PDLNLELRIS), was identified as an efficient inhibitor of chs_H1-activating TFs. Comparative analyses of hop and A. thaliana TFs revealed a complex activation of Pchs_H1 and Pchs4 in combinatorial or independent manners. Conclusions This study on the sequences and functions of various lupulin gland-specific transcription factors provides insight into the complex character of the regulation of the chs_H1 gene that depends on variable activation by combinations of R2R3Myb, bHLH and WDR TF homologues and inhibition by a Myb repressor.

Solid phase extraction, based on the use of color catcher sheets, was successfully employed for the preconcentration of food dyes from alcohol containing beverages. The photos of color catcher sheets with the adsorbed dyes were taken with a mobile phone. The smartphone-based image analysis of the photos was performed using Color Picker application. The values of several color spaces were collected. Specific values from RGB, CMY, RYB and LAB color spaces were proportional to the dye concentration in the analyzed samples. The described inexpensive, simple and elution free assay enables analysis of dyes concentration in various solutions., Competing Interests: Declaration of competing interest The authorsdeclare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Recent studies have underscored the importance of gamma-delta (γδ) T cells in mediating potent MHC-unrestricted cytotoxicity in numerous malignancies. Here, we analyzed Vδ1 and Vδ2 γδ T cell subsets in newly diagnosed chronic myeloid leukemia (CML) patients (n = 40) who had initiated tyrosine kinase inhibitor (TKI) therapy including imatinib (n = 22), nilotinib (n = 14) and dasatinib (n = 4). Patient peripheral blood samples were analyzed at diagnosis and monitored prospectively at 3, 6, 12 and 18 months post-TKI. γδ T cells isolated from healthy donors and CML patients were used against K562, LAMA-84 and KYO-1 cell lines and against primary CML cells in cytotoxicity assays. We found large expansions of Vδ1 and Vδ2 T cells in patients at diagnosis compared to age-matched healthy donors (n = 40) (p < 0.0001). The γδ T cell reconstitution in patients on imatinib and also on nilotinib showed significant reductions of Vδ1 T cell and Vδ2 T cell absolute counts at 3 months compared to diagnosis. Importantly, Vδ1 and Vδ2 T absolute cell counts remained at normal levels from 3 months throughout the follow-up. Next, we observed susceptibility to specific lysis of primary CML tumor cells by Vδ1 T cells from healthy donors. Furthermore, we determined inherent cytotoxic reactivity by autologous patients' Vδ1 T lymphocytes against primary CML tumor cells. Finally, the TCR clonality profiles showed in CML patients mostly polyclonal repertoires regardless of the TKI. Our results provide further evidence into γδ T cell antileukemia immunity in CML that might be beneficial for long-term disease control and treatment outcome., (© 2022. The Author(s).)

Orthopedic implants heal well without complications in most patients but fail for unclear reasons in some individuals. This study determined the relevance of metal hypersensitivity in patients with failed orthopedic implants and those requiring orthopedic implant surgery. The study included 35 patients with failed orthopedic implants and 15 subjects scheduled for orthopedic implant surgery. The production of selected pro-inflammatory cytokines was measured in patients with failed orthopedic implants. Metal hypersensitivity was measured in all subjects using the MELISA® test. Of common metals in orthopedic alloys, the patients with failed orthopedic implants responded most frequently to nickel, chromium, titanium, iron, and molybdenum. Hypersensitivity to metals found in implants was measured in 40% of patients with failed implants. The study also showed that titanium exposure in patients with titanium hypersensitivity might lead to implant failure. Metal hypersensitivity testing should be offered to patients before surgery to minimize the risk of implant failure., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests associated with this publication., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The deficiency of natural anticoagulants—antithrombin (AT), protein C (PC), and protein S (PS)—is a highly predisposing factor for thrombosis, which is still underdiagnosed at the genetic level. We aimed to establish and evaluate an optimal diagnostic approach based on a high-throughput sequencing platform suitable for testing a small number of genes. A fast, flexible, and efficient method involving automated amplicon library preparation and target sequencing on the Ion Torrent platform was optimized. The cohort consisted of a group of 31 unrelated patients selected for sequencing due to repeatedly low levels of one of the anticoagulant proteins (11 AT-deficient, 13 PC-deficient, and 7 PS-deficient patients). The overall mutation detection rate was 67.7%, highest in PC deficiency (76.9%), and six variants were newly detected—SERPINC1 c.398A > T (p.Gln133Leu), PROC c.450C > A (p.Tyr150Ter), c.715G > C (p.Gly239Arg) and c.866C > G (p.Pro289Arg), and PROS1 c.1468delA (p.Ile490fs) and c.1931T > A (p.Ile644Asn). Our data are consistent with those of previous studies, which mostly used time-consuming Sanger sequencing for genotyping, and the indication criteria for molecular genetic testing were adapted to this process in the past. Our promising results allow for a wider application of the described methodology in clinical practice, which will enable a suitable expansion of the group of indicated patients to include individuals with severe clinical findings of thrombosis at a young age. Moreover, this approach is flexible and applicable to other oligogenic panels.

At present, both native and immobilized nanoparticles are of great importance in many areas of science and technology. In this paper, we have studied magnetic iron oxide nanoparticles and their aggregates bound on woven cotton textiles employing two simple modification procedures. One modification was based on the treatment of textiles with perchloric-acid-stabilized magnetic fluid diluted with methanol followed by drying. The second procedure was based on the microwave-assisted conversion of ferrous sulfate at high pH followed by drying. The structure and functional properties of these modified textiles were analyzed in detail. Scanning electron microscopy of native and modified textiles clearly showed the presence of iron oxide nanoparticles on the surface of the modified cotton fibers. All of the modified textile materials exhibited light to dark brown color depending on the amount of the bound iron oxide particles. Magnetic measurements showed that the saturation magnetization values reflect the amount of magnetic nanoparticles present in the modified textiles. Small-angle X-ray and neutron scattering measurements were conducted for the detailed structural characterization at the nanoscale of both the native and magnetically modified textiles, and different structural organization of nanoparticles in the two kinds of textile samples were concluded. The textile-bound iron oxide particles exhibited peroxidase-like activity when the N , N -diethyl- p -phenylenediamine sulfate salt was used as a substrate; this nanozyme activity enabled rapid decolorization of crystal violet in the presence of hydrogen peroxide. The deposition of a sufficient amount of iron oxide particles on textiles enabled their simple magnetic separation from large volumes of solutions; if necessary, the magnetic response of the modified textiles can be simply increased by incorporation of a piece of magnetic iron wire. The simplicity of the immobilized nanozyme preparation and the low cost of all the precursors enable its widespread application, such as decolorization and degradation of selected organic dyes and other important pollutants. Other types of textile-bound nanozymes can be prepared and used as low-cost catalysts for a variety of applications.

Antiphospholipid syndrome (APS) is a hypercoagulation condition associated with the incidence of heterogenic antiphospholipid antibodies (aPLs), which non-specifically affect hemostasis processes. APS is clinically manifested by recurrent arterial and venous thromboses and reproduction losses. The aPL antibodies, which may induce clinical manifestations of APS, include criteria antibodies anti-cardiolipin, anti-β2-glycoprotein-I, and lupus anticoagulant, but also non-criteria antibodies, for example anti-β2-glycoprotein-I domain I, anti-phosphatidylserine/prothrombin, anti-annexin V, and many others. APS occurs mostly in patients of younger and middle age, most frequently in females. Laboratory diagnostics of APS are quite difficult, as they include a wide spectrum of examining methods, which are based on various principles of detection and are performed using various laboratory techniques. The objective of the review is to describe the current state of potentially examined biomarkers and methods in APS diagnostics. The aforementioned biomarkers are lupus anticoagulant, anti-β2-glycoprotein-I, anti-cardiolipin, anti-β2-glycoprotein-I domain I, anti-phosphatidylserine/prothrombin, anti-β2-glycoprotein-I IgA, anti-cardiolipin IgA, anti-annexin V and II, anti-prothrombin, anti-cardiolipin/vimentin, anti-protein S/protein C, and antibodies against phospholipid antigens for whose diagnostics we may use some of the methods established for a long time and some of the modern methods-the coagulation method for the determination of lupus anticoagulant (LA), enzyme-linked imunosorbent assay (ELISA), chemiluminescence analysis (CLIA), multiplex fluorescence flow immunoassay (MFFIA), fluorescence enzyme immunoassay (EliA), line immunoassay (LIA), multiline dot assay (MLDA), and thin-layer chromatography (TLC). Conclusion: Antibodies against phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, cardiolipin/vimentin complex, and annexin V are currently the most studied new markers. However, these assays have not been standardized until now, both from the laboratory and clinical point of view. In this review we summarize the evidence of the most studied aPL markers and their potential clinical significance in seronegative APS (SN-APS).

To evaluate long-term real-life results of dasatinib therapy among chronic phase chronic myeloid leukemia patients resistant or intolerant to imatinib, we retrospectively analyzed data of 118 patients treated in centers participating in the database INFINITY. With median follow-up of 37 months, estimated 5-year cumulative incidences of complete cytogenetic and major molecular responses were 78% and 68%, respectively. The estimated 5-year probability of overall survival (OS) and event-free survival (EFS) were 86% and 83%, respectively. Both OS and EFS were significantly improved among patients with BCR-ABL1 transcript level ≤10% at 3 months. Dasatinib toxicity was tolerable however persistent in almost half our patients, even after years of therapy. Pleural effusion occurred in 29% of patients and was responsible for 30% of dasatinib discontinuations. Our results confirmed very good efficacy and acceptable toxicity of dasatinib in second line setting and support the evidence and importance of high-quality real-life CML patient management.

Recurrent gain-of-function mutations in the transcription factors STAT5A and much more in STAT5B were found in hematopoietic malignancies with the highest proportion in mature T- and natural killer-cell neoplasms (peripheral T-cell lymphoma, PTCL). No targeted therapy exists for these heterogeneous and often aggressive diseases. Given the shortage of models for PTCL, we mimicked graded STAT5A or STAT5B activity by expressing hyperactive Stat5a or STAT5B variants at low or high levels in the hematopoietic system of transgenic mice. Only mice with high activity levels developed a lethal disease resembling human PTCL. Neoplasia displayed massive expansion of CD8 + T cells and destructive organ infiltration. T cells were cytokine-hypersensitive with activated memory CD8 + T-lymphocyte characteristics. Histopathology and mRNA expression profiles revealed close correlation with distinct subtypes of PTCL. Pronounced STAT5 expression and activity in samples from patients with different subsets underline the relevance of JAK/STAT as a therapeutic target. JAK inhibitors or a selective STAT5 SH 2 domain inhibitor induced cell death and ruxolitinib blocked T-cell neoplasia in vivo We conclude that enhanced STAT5A or STAT5B action both drive PTCL development, defining both STAT5 molecules as targets for therapeutic intervention., (Copyright© 2020 Ferrata Storti Foundation.)