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Metal matrix composite (MMC) surface layers reinforced by WC were fabricated on armor steel ARMOX 500T plates via a laser surface alloying process. The microstructure of the layers was assessed by scanning electron microscopy and X-ray diffraction.

Abstract Background Flavonoids are a group of secondary plant metabolites important for plant growth and development. They show also a protective effect against colon and breast cancer, diabetes, hypercholesterolemic atherosclerosis, lupus nephritis, and immune and inflammatory reactions. Thus, overproduction of these compounds in flax by genetic engineering method might potentiate biotechnological application of these plant products. Results Flax plants of third generation overexpressing key genes of flavonoid pathway cultivated in field were used as plant material throughout this study. The biochemical properties of seed, oil and seedcake extracts and fibre from natural and transgenic flax plants were compared. The data obtained suggests that the introduced genes were stably inherited and expressed through plant generations. Overproduction of flavonoid compounds resulted in increase of fatty acids accumulation in oil from transgenic seeds due to protection from oxidation offered during synthesis and seed maturation. The biochemical analysis of seedcake extracts from seeds of transgenic flax revealed significant increase in flavonoids (kaempferol), phenolic acids (coumaric, ferulic, synapic acids) and lignan content. Fibres, another product of flax plant showed increase in the level of catechine and acetylvanillone and decrease in phenolic acids upon flax modification. Biochemical analysis results were confirmed using IR spectroscopy. The integral intensities of IR bands have been used for identification of the component of phenylpropanoid pathway in oil, seedcake extract and fibre from control and transgenic flax. It was shown that levels of flavonoids, phenolic acids and lignans in oil and seedcake extract was higher in transgenic flax products compared to control. An FT-IR study of fibres confirmed the biochemical data and revealed that the arrangement of the cellulose polymer in the transgenic fibres differs from the control; in particular a significant decrease in the number of hydrogen bonds was detected. Conclusions All analysed products from generated transgenic plants were enriched with antioxidant compounds derived from phenylopropanoid pathway Thus the products provide valuable source of flavonoids, phenolic acids and lignan for biomedical application. The compounds composition and quantity from transgenic plants was confirmed by IR spectroscopy. Thus the infrared spectroscopy appeared to be suitable method for characterization of flax products.

The recently created six transgenic potato genotypes with overexpressed or underexpressed P14-3-3a (29G) and P14-3-3c (20R) isoforms of 14-3-3 protein were field-trialled (1998–2001). The contents of protein, starch, reducing sugars, sucrose and lipids were determined in the transgenic and control tubers harvested from the field. The obtained results showed a significant increase in crude protein content in potatoes with repression of P14-3-3c isoform and in potatoes with blocked P14-3-3a synthesis in comparison to the control line. A stable increase in lipid content of potatoes with overexpression of 14-3-3 protein from Cucurbita pepo in the field trials was observed. The variability of the investigated genotypes, in respect to the nutritional components, was statistically analysed using discriminant function and cluster analyses. The dominant influence of the variability of the genotypes exerted significant differentiation of protein, lipid and starch contents. These components showed the greatest discriminant power in the variability of genotypes. These results confirm the suggestion that 14-3-3 protein co-ordinates primary metabolite synthesis in plants. [Copyright &y& Elsevier]

Ocimum basilicum is a valuable plant widely consumed worldwide and considered a rich source of polyphenols. This study examined the impact of the polyphenolic fraction isolated from basil (ObF) on human normal colon epithelial cells and human colorectal adenocarcinoma cells, evaluating its anti-inflammatory and protective activity against oxidative stress. The phytochemical characterization of the fraction was performed using ultra-performance liquid chromatography (UPLC) with a photodiode detector (DAD) and mass spectrometry (MS). UPLC-DAD-MS revealed that ObF predominantly contains caffeic acid derivatives, with rosmarinic acid and chicoric acid being the most abundant. The fraction demonstrated high antioxidant potential, as shown by DPPH assays, along with significant reducing power (FRAP). Furthermore, it prevented the depletion of antioxidant enzymes, including superoxide dismutase and catalase, and decreased malonylodialdehyde (MDA) in induced oxidative stress condition. Additionally, it exhibited a significant protective effect against H 2 O 2 -induced cytotoxicity in human normal colon epithelial cells. Although it had no impact on the viability of adenocarcinoma cells, it significantly reduced IL-1β levels in the neoplastic microenvironment. Our study demonstrated that basil polyphenols provide significant health benefits due to their antioxidant and protective activities.

Urtica dioica L. is one of the most widely utilized medicinal plants commonly applied in the form of tea, juice, and dietary supplements. This study aimed to assess the effect of the U. dioica ethanol-water extract (UdE) and polyphenolic fraction isolated from the extract (UdF) on normal human colon epithelial cells and to evaluate their protective activity against induced oxidative stress. The cytotoxic potential against human colorectal adenocarcinoma (HT29) and the anti-inflammatory effects were also investigated. UPLC-MS-DAD analysis revealed that both extracts were abundant in caffeic acid derivatives, specifically chlorogenic and caffeoylmalic acids, and therefore, they showed significant protective and ROS scavenging effects in normal human colon epithelial cells. Moreover, they had no negative impact on cell viability and morphology in normal cells and the extracts, particularly UdF, moderately suppressed adenocarcinoma cells. Furthermore, UdF significantly decreased IL-1β levels in HT29 cells. Our research indicates that U. dioica may provide significant health advantages because of its antioxidant and anti-inflammatory effects., Competing Interests: The authors declare no conflicts of interest.

Tiliroside is a natural polyphenolic compound with a wide range of biological activity, and defatted strawberry seeds are its rich source. The goal of this study was to optimize accelerated solvent extraction (ASE) conditions, including temperature, solvent composition, and the number of extraction cycles, using Box-Behnken design to maximize the yield of tiliroside. UPLC-DAD-MS was applied to investigate the polyphenolic composition of the extracts, and preparative liquid chromatography (pLC) was used for isolation. All obtained mathematical models generally showed an increase in the efficiency of isolating polyphenolic compounds with an increase in temperature, ethanol content, and the number of extraction cycles. The optimal established ASE conditions for tiliroside were as follows: a temperature of 65 °C, 63% ethanol in water, and four extraction cycles. This allowed for the obtainment of a tiliroside-rich fraction, and the recovery of isolated tiliroside from plant material reached 243.2 mg from 100 g. Our study showed that ASE ensures the isolation of a tiliroside-rich fraction with high effectiveness. Furthermore, defatted strawberry seeds proved to be a convenient source of tiliroside because the matrix of accompanying components is relatively poor, which facilitates separation.

The article presents research results on the possibility of shaping the structure and properties of Co-Cr-W-C-Ti alloys (type Stellite 6) using laser cladding technology. Cobalt-based alloys are used in several industries because they are characterized by high erosion, abrasion, and corrosion resistance, retaining these properties at high temperatures. To further increase erosion resistance, it seems appropriate to reinforce material by in situ synthesis of hard phases. Among the transition metal carbides (TMCs), titanium carbide is one of the hardest and can have a positive effect on the extension of the lifetime of components made from cobalt-based alloys. In this article, concentration of C, W, and Ti due to the possibility of in situ synthesis of titanium carbides was subjected to detailed analysis. The provided research includes macrostructure and microstructure analysis, X-ray diffraction (XRD), microhardness, and penetrant tests. It was found that the optimal concentrations of Ti and C in the Co-Cr-W-C alloy allow the formation of titanium carbides, which significantly improves erosion resistance for low impact angles. Depending on the concentrations of titanium, carbon, and tungsten in the molten metal pool, it is possible to shape the alloy structure by influencing to morphology and size of the reinforcing phase in the form of the complex carbide (Ti,W)C.

Urtica dioica is a species with well-established significance in folk medicine in many countries. It was utilized to support the treatment of arthritis, allergies, and urinary tract disorders; however, the substantial presence of antioxidants suggests that nettle extract could also have a positive impact on the skin. The objective of this study was to assess the impact of nettle extract on human skin fibroblasts subjected to oxidative stress. Various solvents were tested to prepare an extract rich in polyphenolic compounds with high antioxidant potential. The chemical composition was determined using ultra-high-performance liquid chromatography with mass spectrometry (UPLC-DAD-MS). H 2 O 2 treatment was used to induce oxidative stress and cell viability, and the metabolism was evaluated through NR and MTT assays. Our study demonstrated that extraction with 80% ethanol, followed by the drying and re-dissolving of the extract in pure water, was more efficient than direct extraction with water. This yielded an extract rich in polyphenolic compounds, with chlorogenic acid and caffeoylmalic acid as the predominant compounds, averaging 64.9 and 114.4 µg/mL, respectively. The extract exhibited antioxidant properties in the DPPH and ABTS assays. Furthermore, it did not exhibit cytotoxicity and did not negatively affect cell metabolism. In addition, it effectively reduced ROS in the H 2 O 2 -stimulated cells, and at the highest concentration tested, the ROS levels returned to those of the untreated control. The extract also protected against H 2 O 2 -induced cytotoxicity. The cell viability was maintained at the level of the untreated control when the cells were pretreated with the extract before H 2 O 2 exposure. These findings indicate that U. dioica extract is a valuable and safe additive in skincare products.

Introduction: Polycythemia vera (PV) and essential thrombocythemia (ET) are diseases driven by canonical mutations in JAK2, CALR, or MPL gene. Previous studies revealed that in addition to driver mutations, patients with PV and ET can harbor other mutations in various genes, with no established impact on disease phenotype. We hypothesized that the molecular profile of patients with PV and ET is dynamic throughout the disease., Methods: In this study, we performed a 37-gene targeted next-generation sequencing panel on the DNA samples collected from 49 study participants in two-time points, separated by 78-141 months. We identified 78 variants across 37 analyzed genes in the study population., Results: By analyzing the change in variant allele frequencies and revealing the acquisition of new mutations during the disease, we confirmed the dynamic nature of the molecular profile of patients with PV and ET. We found connections between specific variants with the development of secondary myelofibrosis, thrombotic events, and response to treatment. We confronted our results with existing conventional and mutation-enhanced prognostic systems, showing the limited utility of available prognostic tools., Discussion: The results of this study underline the significance of repeated molecular testing in patients with PV and ET and indicate the need for further research within this field to better understand the disease and improve available prognostic tools., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sobieralski, Wasąg, Leszczyńska, Żuk and Bieniaszewska.)

Familial hypercholesterolemia (FH) is an autosomal-dominant disorder caused mainly by substitutions in the low-density lipoprotein receptor ( LDLR ) gene, leading to an increased risk of premature cardiovascular diseases. Tremendous advances in sequencing techniques have resulted in the discovery of more than 3000 variants of the LDLR gene, but not all of them are clinically relevant. Therefore, functional studies of selected variants are needed for their proper classification. Here, a single-cell, kinetic, fluorescent LDL uptake assay was applied for the functional analysis of LDLR variants in a model of an LDLR-deficient human cell line. An LDLR-defective HEK293T cell line was established via a CRISPR/Cas9-mediated luciferase-puromycin knock-in. The expressing vector with the LDLR gene under the control of the regulated promoter and with a reporter gene has been designed to overproduce LDLR variants in the host cell. Moreover, an LDLR promoter-luciferase knock-in reporter system has been created in the human cell line to study transcriptional regulation of the LDLR gene, which can serve as a simple tool for screening and testing new HMG CoA reductase-inhibiting drugs for atherosclerosis therapy. The data presented here demonstrate that the obtained LDLR-deficient human cell line HEK293T-ldlrG1 and the dedicated pTetRedLDLRwt expression vector are valuable tools for studying LDL internalization and functional analysis of LDLR and its genetic variants. Using appropriate equipment, LDL uptake to a single cell can be measured in real time. Moreover, the luciferase gene knock-in downstream of the LDLR promotor allows the study of promoter regulation in response to diverse conditions or drugs. An analysis of four known LDLR variants previously classified as pathogenic and benign was performed to validate the LDLR-expressing system described herein with the dedicated LDLR-deficient human cell line, HEK293T-ldlrG1.

Purpose: The work presents outcomes of simulated maxillofacial skeleton osteotomies supported with cutting guides or one of two AR-based intraoperative navigation systems., Material and Methods: The series of osteotomies supported with a cutting guide, simple AR (sAR) or navigated AR (nAR) module were carried out on 15 (five per each method) skull models according to the virtual surgical plan (VSP). Each method was used to support 40 osteotomies involving the upper jaw and 40 involving the orbital region (16 osteotomies on each model). Postoperative computed tomography scans were fused with the VSP to analyse angular deviations from the planned cutting trajectory (°) and the deviations of labelled control points (mm)., Results: Guides provided the highest accuracy, with a mean osteotomy angular deviation of 3.73 ± 2.94° and a mean control point deviation of 1.30 ± 0.73 mm. Mean angular deviations for the sAR- and nAR-assisted osteotomies were 5.93 ± 5.12° and 6.75 ± 5.33°, and mean control point deviations amounted to 1.86 ± 0.88 mm and 1.97 ± 0.70 mm., (© 2023 John Wiley & Sons Ltd.)

Beta-ketothiolases are involved in the beta-oxidation of fatty acids and the metabolism of hormones, benzenoids, and hydroxybutyrate. The expression of bacterial beta-ketothiolase in flax ( Linum usitatissimum L.) results in an increase in endogenous beta-ketothiolase mRNA levels and beta-hydroxybutyrate content. In the present work, the effect of overexpression of beta-ketothiolase on retting and stem and fibre composition of flax plants is presented. The content of the components was evaluated by high-performance liquid chromatography, gas chromatography-mass spectrometry, Fourier-transform infrared spectroscopy, and biochemical methods. Changes in the stem cell walls, especially in the lower lignin and pectin content, resulted in more efficient retting. The overexpression of beta-ketothiolase reduced the fatty acid and carotenoid contents in flax and affected the distribution of phenolic compounds between free and cell wall-bound components. The obtained fibres were characterized by a slightly lower content of phenolic compounds and changes in the composition of the cell wall. Based on the IR analysis, we concluded that the production of hydroxybutyrate reduced the cellulose crystallinity and led to the formation of shorter but more flexible cellulose chains, while not changing the content of the cell wall components. We speculate that the changes in chemical composition of the stems and fibres are the result of the regulatory properties of hydroxybutyrate. This provides us with a novel way to influence metabolic composition in agriculturally important crops.

This study was performed to synthesize a radiopharmaceutical designed for multimodal hepatocellular carcinoma (HCC) treatment involving radionuclide therapy and magnetic hyperthermia. To achieve this goal, the superparamagnetic iron oxide (magnetite) nanoparticles (SPIONs) were covered with a layer of radioactive gold ( 198 Au) creating core-shell nanoparticles (SPION@Au). The synthesized SPION@Au nanoparticles exhibited superparamagnetic properties with a saturation magnetization of 50 emu/g, which is lower than reported for uncoated SPIONs (83 emu/g). Nevertheless, the SPION@Au core-shell nanoparticles showed a sufficiently high saturation magnetization value which allows them to reach a temperature of 43 °C at a magnetic field frequency of 386 kHz. The cytotoxic effect of nonradioactive and radioactive SPION@Au-polyethylene glycol (PEG) bioconjugates was carried out by treating HepG2 cells with various concentrations (1.25-100.00 µg/mL) of the compound and radioactivity in range of 1.25-20 MBq/mL. The moderate cytotoxic effect of nonradioactive SPION@Au-PEG bioconjugates on HepG2 was observed. The cytotoxic effect associated with the β - radiation emitted by 198 Au was much greater and already reaches a cell survival fraction below 8% for 2.5 MBq/mL of radioactivity after 72 h. Thus, the killing of HepG2 cells in HCC therapy should be possible due to the combination of the heat-generating properties of the SPION- 198 Au-PEG conjugates and the radiotoxicity of the radiation emitted by 198 Au.

Oligo technology is a low-cost and easy-to-implement method for direct manipulation of gene activity. The major advantage of this method is that gene expression can be changed without requiring stable transformation. Oligo technology is mainly used for animal cells. However, the use of oligos in plants seems to be even easier. The oligo effect could be similar to that induced by endogenous miRNAs. In general, the action of exogenously introduced nucleic acids (Oligo) can be divided into a direct interaction with nucleic acids (genomic DNA, hnRNA, transcript) and an indirect interaction via the induction of processes regulating gene expression (at the transcriptional and translational levels) involving regulatory proteins using endogenous cellular mechanisms. Presumed mechanisms of oligonucleotides' action in plant cells (including differences from animal cells) are described in this review. Basic principles of oligo action in plants that allow bidirectional changes in gene activity and even those that lead to heritable epigenetic changes in gene expression are presented. The effect of oligos is related to the target sequence at which they are directed. This paper also compares different delivery methods and provides a quick guide to using IT tools to help design oligonucleotides.

The development trends in the energy sector clearly indicate an increase in the share of biomass and alternative fuels fed for combustion in power boilers, which results in the imposition of many unfavourable factors and a demanding working environment. During the operation of the energy system, this means a sharp increase in corrosion of the gas-tight pipe walls and coils by the destructive action of chlorine and sulphur. Implementing advanced surface protection in addition to the selection of materials of better quality and resistance to difficult working conditions would significantly reduce their wear by high temperature corrosion. Thermally sprayed coatings offer a great opportunity to protect machine components and energy systems against corrosion, erosion, impact load and abrasive wear. This article presents the test results of high-temperature corrosion resistance of coatings made with Ni-Cr-B-Si and Ni-B-Si alloy powders on a boiler steel substrate. Samples with sprayed coatings were exposed to an atmosphere with a composition of N 2 + 9% O 2 + 0.08% SO 2 + 0.15% HCl at 800 °C for 250, 500, 750 and 1000 h. Tests results of coatings made of Ni-Cr-B-Si alloys subjected to the influence of a corrosive environment showed the formation of a layer of scale on the surface, composed mainly of Cr 2 O 3 oxide, which was a passive layer, reducing the rate of corrosion. Coatings sprayed with Ni-B-Si alloys showed significantly lower corrosion resistance. It was found that the developed technology of subsonic flame spraying with powders of the Ni-Cr-B-Si type allows the production of coatings compliant with the requirements of the energy industry, which allows their use as anti-corrosion protection on boiler elements intended for waste disposal and biomass combustion.

Purpose: The "image to patient" registration procedure is crucial for the accuracy of surgical instrument tracking relative to the medical image while computer-aided surgery. The main aim of this work was to create an equal-resolution surface registration algorithm (ERSR) and analyze its efficiency., Methods: The ERSR algorithm provides two datasets with equal, high resolution and approximately corresponding points. The registered sets are obtained by projection of a user-designed rectangle(s)-shaped uniform clouds of points on DICOM and surface scanner datasets. The tests of the algorithm were performed on a phantom with titanium microscrews. We analyzed the influence of DICOM resolution on the effect of the ERSR algorithm and compared the ERSR to standard paired-points landmark transform registration. The methods of analysis were Target Registration Error, distance maps, and their histogram evaluation., Results: The mean TRE in case of ERSR equaled 0.8 ± 0.3 mm (resolution A), 0.8 ± 0.5 mm (resolution B), and 1.0 ± 0.7 mm (resolution C). The mean values were at least 0.4 mm lower than in the case of landmark transform registration. The distance maps between the model achieved from the scanner and the CT-based model were analyzed by histogram. The frequency of the first bin in a histogram of the distance map for ERSR was about 0.6 for all three resolutions of DICOM dataset and three times higher than in the case of landmark transform registration. The results were statistically analyzed using the Wilcoxon signed-rank test (alpha = 0.05)., Conclusion: The tests proved a statistically significant higher efficiency of equal resolution surface registration related to the landmark transform algorithm. It was proven that the lower resolution of the CT DICOM dataset did not degrade the efficiency of the ERSR algorithm. We observed a significantly lower response to decreased resolution than in the case of paired-points landmark transform registration., (© 2022. The Author(s).)

Purpose: The authors of the current study aimed to propose a calibration method for accurate augmented reality visualisation using an optical see-through head-mounted display, and to qualitatively evaluate visualisation accuracy for the application in computer assisted surgery., Methods: An adaptation of stereo single-point active alignment method was proposed as the calibration procedure together with verification. Three tests were performed: display of points in 3D space, on the plane and on the surface of a skull phantom on inexperience users (5 participants) and experienced users (17 participants)., Results: The highest accuracy of visualization was obtained for skull phantom visualisation for an inexperienced user (3.00 mm, std 0.75 mm), while the lowest accuracy was obtained in a 3D visualisation test for an inexperienced user (22.95 mm, std 18.04 mm). The largest error was related to the depth component and amounted to 18.49 mm, std 18.10 mm for an inexperienced user., Conclusions: It is possible to achieve relatively high visualisation accuracy (less than 5 mm for visualisation in space) for selected users but providing it for the group of inexperienced users seems to remain a major challenge. The accuracy of point indication can be substantially and statistically significantly increased by visualising objects on surfaces. The proposed methods and obtained results can serve as a basis for further implementation of augmented reality visualisation on an optical see-through head-mounted display in applications requiring high-quality augmented reality guidance of manual tasks.

Introduction: Brain metastases (BM) severely affect the prognosis and quality of life of patients with NSCLC. Recently, molecularly targeted agents were found to have promising activity against BM in patients with NSCLC whose primary tumors carry "druggable" mutations. Nevertheless, it remains critical to identify specific pathogenic alterations that drive NSCLC-BM and that can provide novel and more effective therapeutic targets., Methods: To identify potentially targetable pathogenic alterations in NSCLC-BM, we profiled somatic copy number alterations (SCNAs) in 51 matched pairs of primary NSCLC and BM samples from 33 patients with lung adenocarcinoma and 18 patients with lung squamous cell carcinoma. In addition, we performed multiregion copy number profiling on 15 BM samples and whole-exome sequencing on 40 of 51 NSCLC-BM pairs., Results: BM consistently had a higher burden of SCNAs compared with the matched primary tumors, and SCNAs were typically homogeneously distributed within BM, suggesting BM do not undergo extensive evolution once formed. By comparing focal SCNAs in matched NSCLC-BM pairs, we identified putative BM-driving alterations affecting multiple cancer genes, including several potentially targetable alterations in genes such as CDK12 , DDR2 , ERBB2 , and NTRK1 , which we validated in an independent cohort of 84 BM samples. Finally, we identified putative pathogenic alterations in multiple cancer genes, including genes involved in epigenome editing and 3D genome organization, such as EP300 , CTCF , and STAG2 , which we validated by targeted sequencing of an independent cohort of 115 BM samples., Conclusions: Our study represents the most comprehensive genomic characterization of NSCLC-BM available to date, paving the way to functional studies aimed at assessing the potential of the identified pathogenic alterations as clinical biomarkers and targets., (© 2022 The Authors.)

Background: Infants with duct dependent heart lesions often require invasive procedures during the neonatal or early infancy period. These patients remain a challenge for pediatric cardiologists, neonatologists, and intensive care unit personnel. A relevant portion of these infant suffer from respiratory, cardiac failure and may develop NEC, which leads to inadequate growth and nutrition, causing delayed or complicated cardiac surgery., Methods: This randomized control trial will recruit term infants diagnosed with a duct dependant lesion within the first 72 h of life. After obtaining written parental consent patients will be randomized to either the physician led enteral feeding or protocol-based feeding group. The intervention will continue up to 28 days of life or day of cardiosurgical treatment, whichever comes first. The primary outcomes include NEC and death related to NEC. Secondary outcomes include among others, number of interrupted feedings, growth velocity, daily protein and caloric intake, days to reach full enteral feeding and on mechanical ventilation., Discussion: Our study will be the first randomized control trial to evaluate if standard (as in healthy newborns) initiation and advancement of enteral feeding is safe, improves short term outcomes and does not increase the risk of NEC. If the studied feeding regime proves to be intact, swift implementation and advancement of enteral nutrition may become a recommendation., Trial Registration: The study protocol has been approved by the local ethical board. It is registered at ClinicalTrials.gov NCT05117164., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Seliga-Siwecka, Płotko, Wójcik-Sep, Bokiniec, Latka-Grot, Żuk, Furmańczyk, Zieliński and Chrzanowska.)

Development of secondary CML has only been casually described, with few reports attempting to analyze and explain the mechanisms behind this phenomenon. Reported cases vary with regard to presumed pathogenesis and clinical characteristics, but similarities can be observed. This report presents the case of a patient diagnosed with CALR and ASXL1-mutated primary myelofibrosis who developed CML 13 years after the initial diagnosis. In contrast with previously reported cases, this patient did not have JAK2 or ABL1 gene mutations, and also exhibited primary resistance to tyrosine kinase inhibitor (TKI) treatment. Here, we analyze the molecular evolution of CML and describe successful treatment with concomitant therapy including a TKI and JAK inhibitor. This report aims to deepen clinical experience and further broaden knowledge about chronic myeloproliferative neoplasms., (© 2022. Japanese Society of Hematology.)