MTF2 facilitates the advancement of osteosarcoma through mediating EZH2/SFRP1/Wnt signaling.

BACKGROUND: Osteosarcoma is a soft tissue neoplasm with elevated recurrence risk and highly metastatic potential. Metal response element binding transcriptional factor 2 (MTF2) has been revealed to exert multiple activities in human tissues. The present research was conducted to explore the functions and related response mechanism of MTF2 in osteosarcoma which have not been introduced yet. METHODS: Bioinformatics tools identified the differential MTF2 expression in osteosarcoma tissues. MTF2 expression in osteosarcoma cells was examined with Western blot. Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-2'-deoxyuridine (EDU) staining, wound healing as well as transwell assays measured cell proliferation, migration and invasion, respectively. Flow cytometry assay detected the cellular apoptotic level. Western blot also measured the expressions of proteins associated with epithelial mesenchymal transition (EMT), apoptosis and enhancer of zeste homolog 2 (EZH2)/secreted frizzled-related protein 1 (SFRP1)/Wnt signaling. Co-immunoprecipitation (Co-IP) assay confirmed MTF2-EZH2 interaction. RESULTS: MTF2 expression was increased in osteosarcoma tissues and cells. MTF2 interference effectively inhibited the proliferation, migration and invasion of osteosarcoma cells and promoted the cellular apoptotic rate. MTF2 directly bound to EZH2 and MTF2 silence reduced EZH2 expression, activated SFRP1 expression and blocked Wnt signaling in osteosarcoma cells. EZH2 upregulation or SFRP1 antagonist WAY-316606 partly counteracted the impacts of MTF2 down-regulation on the SFRP1/Wnt signaling and the biological phenotypes of osteosarcoma cells. CONCLUSIONS: MTF2 might down-regulate SFRP1 to activate Wnt signaling and drive the progression of osteosarcoma via interaction with EZH2 protein.

Use of Multiple-Choice Items in Summative Examinations: Questionnaire Survey Among German Undergraduate Dental Training Programs.

Background: Multiple-choice examinations are frequently used in German dental schools. However, details regarding the used item types and applied scoring methods are lacking. Objective: This study aims to gain insight into the current use of multiple-choice items (ie, questions) in summative examinations in German undergraduate dental training programs. Methods: A paper-based 10-item questionnaire regarding the used assessment methods, multiple-choice item types, and applied scoring methods was designed. The pilot-tested questionnaire was mailed to the deans of studies and to the heads of the Department of Operative/Restorative Dentistry at all 30 dental schools in Germany in February 2023. Statistical analysis was performed using the Fisher exact test (P<.05). Results: The response rate amounted to 90% (27/30 dental schools). All respondent dental schools used multiple-choice examinations for summative assessments. Examinations were delivered electronically by 70% (19/27) of the dental schools. Almost all dental schools used single-choice Type A items (24/27, 89%), which accounted for the largest number of items in approximately half of the dental schools (13/27, 48%). Further item types (eg, conventional multiple-select items, Multiple-True-False, and Pick-N) were only used by fewer dental schools (≤67%, up to 18 out of 27 dental schools). For the multiple-select item types, the applied scoring methods varied considerably (ie, awarding [intermediate] partial credit and requirements for partial credit). Dental schools with the possibility of electronic examinations used multiple-select items slightly more often (14/19, 74% vs 4/8, 50%). However, this difference was statistically not significant (P=.38). Dental schools used items either individually or as key feature problems consisting of a clinical case scenario followed by a number of items focusing on critical treatment steps (15/27, 56%). Not a single school used alternative testing methods (eg, answer-until-correct). A formal item review process was established at about half of the dental schools (15/27, 56%). Conclusions: Summative assessment methods among German dental schools vary widely. Especially, a large variability regarding the use and scoring of multiple-select multiple-choice items was found.

Metallothionein 3 Potentiates Pulmonary Artery Smooth Muscle Cell Proliferation by Promoting Zinc-MTF1-ATG5 Axis-mediated Autophagosome Formation.

Abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is one of the critical pathological mechanisms of pulmonary hypertension (PH), and therefore is gradually being adopted as an important direction for the treatment of PH. Metallothioneins (MTs) have been reported to be associated with PH, but the underlying mechanisms are not fully understood. Here, we demonstrated that the expression level of metallothionein 3 (MT3) was significantly increased in pulmonary arterioles from PH patients and chronic hypoxia-induced rat and mouse PH models, as well as in hypoxia-treated human PASMCs. Knockdown of MT3 significantly inhibited the proliferation of human PASMCs by arresting the cell cycle in the G1 phase, while overexpression of MT3 had the opposite effect. Mechanistically, we found that MT3 increased the intracellular zinc (Zn2+) concentration to enhance the transcriptional activity of metal-regulated transcription factor 1 (MTF1), which promoted the expression of autophagy-related gene 5 (ATG5), facilitating autophagosome formation. More importantly, MT3-induced autophagy and proliferation of human PASMCs were largely prevented by knockdown of MTF1 and ATG5. Therefore, in this study, we identified MT3-Zinc-MTF1-ATG5 as a novel pathway that affects PASMC proliferation by regulating autophagosome formation, suggesting that MT3 may be a novel target for the treatment of PH.

MTF1 genetic variants are associated with lung cancer risk in the Chinese Han population.

BACKGROUND: Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates in the formation and progression of tumors, including lung cancer (LC). The expression level of MTF1 is down-regulated in LC, and high expression of MTF1 is associated with a good prognosis of LC. However, the association between MTF1 polymorphism and LC risk has not been explored. METHODS: The genotyping of MTF1 Single nucleotide polymorphisms (SNPs) including rs473279, rs28411034, rs28411352, and rs3748682 was identified by the Agena MassARRAY system among 670 healthy controls and 670 patients with LC. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistics regression to assess the association of these SNPs with LC risk. RESULTS: MTF1 rs28411034 (OR 1.22, 95% CI 1.03-1.45, p = 0.024) and rs3748682 (OR 1.24, 95% CI 1.04-1.47, p = 0.014) were associated with higher LC susceptibility overall. Moreover, the effect of rs28411034 and rs3748682 on LC susceptibility was observed in males, subjects with body mass index (BMI) ≥ 24 kg/m2, smokers, drinkers, and patients with lung squamous carcinoma (OR and 95% CI > 1, p < 0.05). Besides, rs28411352 (OR 0.73, 95% CI 0.55-0.97, p = 0.028,) showed protective effect for reduced LC risk in drinkers. CONCLUSIONS: We were first who reported that rs28411034 and rs3748682 tended to be relevant to increased LC susceptibility among the Chinese Han population. These results of this study could help to recognize the pathogenic mechanisms of the MTF1 gene in LC progress.

Quantitative assessment of full-width at half-maximum and detector energy threshold in X-ray imaging systems.

BACKGROUND: The response function of imaging systems is regularly considered to improve the qualified maps in various fields. More the accuracy of this function, the higher the quality of the images. METHODS: In this study, a distinct analytical relationship between full-width at half-maximum (FWHM) value and detector energy thresholds at distinct tube peak voltage of 100 kV has been addressed in X-ray imaging. The outcomes indicate that the behavior of the function is exponential. The relevant cut-off frequency and summation of point spread function S(PSF) were assessed at large and detailed energy ranges. RESULTS: A compromise must be made between cut-off frequency and FWHM to determine the optimal model. By detailed energy range, the minimum and maximum of S(PSF) values were revealed at 20 keV and 48 keV, respectively, by 2979 and 3073. Although the maximum value of FWHM occurred at the energy of 48 keV by 224 mm, its minimum value was revealed at 62 keV by 217 mm. Generally, FWHM value converged to 220 mm and S(PSF) to 3026 with small fluctuations. Consequently, there is no need to increase the voltage of the X-ray tube after the energy threshold of 20 keV. CONCLUSION: The proposed FWHM function may be used in designing the setup of the imaging parameters in order to reduce the absorbed dose and obtain the final accurate maps using the related mathematical suggestions.

American College of Medical Toxicology Research Agenda 2024-2030.

ACMT recognizes the pivotal role of high-quality research in advancing medical science. As such, the establishment of a formal research agenda for ACMT is a leap forward in communicating the priorities of the College, its members, and the patient populations we serve. This thoughtfully crafted agenda will serve as a strategic compass for ACMT, guiding our pursuit of scientific discovery, fostering innovation, and enhancing outcomes for patients and communities affected by poisonings and exposures.

PSF and MTF from a bar pattern in digital mammography.

Background.The MTF has difficulties being determined (according to the provisions of the IEC standards) in the hospital setting due to the lack of resources.Purpose.The objective of this work is to propose a quantitative method for obtaining the point spread function (PSF) and the modulation transfer function (MTF) of a digital mammography system from an image of a bar pattern.Methods.The method is based on the measurement of the contrast transfer function (CTF) of the system over the image of the bar pattern. In addition, a theoretical model for thePSFis proposed, from which the theoreticalCTFof the system is obtained by means of convolution with a square wave (mathematical simulation of the bar pattern). Through an iterative process, the free parameters of thePSFmodel are varied until the experimentalCTFcoincides with the one calculated by convolution. Once thePSFof the system is obtained, we calculate theMTFby means of its Fourier transform. TheMTFcalculated from the modelPSFhave been compared with those calculated from an image of a 65µm diameter gold wire using an oversampling process.Results.TheCTFhas been calculated for three digital mammographic systems (DMS 1, DMS 2 and DMS 3), no differences of more than 5 % were found with the CTF obtained with the PSF model. The comparison of theMTFshows us the goodness of thePSFmodel.Conclusions.The proposed method for obtainingPSFandMTFis a simple and accessible method, which does not require a complex configuration or the use of phantoms that are difficult to access in the hospital world. In addition, it can be used to calculate other magnitudes of interest such as the normalized noise power spectrum (NNPS) and the detection quantum efficiency (DQE).

An Online Digital Imaging Excitation Sensor for Wind Turbine Gearbox Wear Condition Monitoring Based on Adaptive Deep Learning Method.

This paper designed and developed an online digital imaging excitation sensor for wind power gearbox wear condition monitoring based on an adaptive deep learning method. A digital imaging excitation sensing image information collection architecture for magnetic particles in lubricating oil was established to characterize the wear condition of mechanical equipment, achieving the real-time online collection of wear particles in lubricating oil. On this basis, a mechanical equipment wear condition diagnosis method based on online wear particle images is proposed, obtaining data from an engineering test platform based on a wind power gearbox. Firstly, a foreground segmentation preprocessing method based on the U-Net network can effectively eliminate the interference of bubbles and dark fields in online wear particle images, providing high-quality segmentation results for subsequent image processing, A total of 1960 wear particle images were collected in the experiment, the average intersection union ratio of the validation set is 0.9299, and the accuracy of the validation set is 0.9799. Secondly, based on the foreground segmentation preprocessing of wear particle images, by using the watered algorithm to obtain the number of particles in each size segment, we obtained the number of magnetic particle grades in three different ranges: 4-38 µm, 39-70 µm, and >70 µm. Thirdly, we proposed a method named multidimensional transformer (MTF) network. Mean Square Error (MSE), Root Mean Square Error (RMSE), and Mean Absolute Error (MAE) are used to obtain the error, and the maintenance strategy is formulated according to the predicted trend. The experimental results show that the predictive performance of our proposed model is better than that of LSTM and TCN. Finally, the online real-time monitoring system triggered three alarms, and at the same time, our offline sampling data analysis was conducted, the accuracy of online real-time monitoring alarms was verified, and the gearbox of the wind turbine was shut down for maintenance and repair.

Cuproptosis-associated genes (CAGs) contribute to the prognosis prediction and potential therapeutic targets in hepatocellular carcinoma.

BACKGROUND: Cuproptosis is a novel form of cell death that exhibits close association with mitochondrial respiration and occurs through distinct mechanisms compared to previously characterized forms of cell death. However, the precise impact of cuproptosis-associated genes (CAGs) on prognosis, immune profiles, and treatment efficacy in hepatocellular carcinomas (HCC) remains poorly understood. METHODS: A comprehensive analysis of CAGs in hepatocellular carcinoma (HCC) prognosis was conducted using genomic data from HCC patients. Consensus clustering analysis was performed to determine molecular subtypes related to cuproptosis in HCC. The single-sample gene set enrichment analysis (ssGSEA) algorithm was applied to quantify the infiltration levels of immune cells, while the "ESTIMATE" package was employed to calculate tumor purity, stromal scores, and immune scores in the tumor microenvironment (TME). Principal component analysis (PCA) algorithm was utilized to construct a risk score related to CAGs. Finally, CCK8, wound healing, Transwell migration/invasion, EDU and xenograft model were employed to explore the potential oncogenic role of MTF1. RESULTS: Three distinct patterns of cuproptosis modification were identified, each associated with unique functional enrichments, clinical characteristics, immune cell infiltration, immune checkpoints, tumor microenvironment (TME), and prognosis. A CAGs-related risk score (Cuscore) was developed to predict prognosis in TCGA and validated in GSE76427 and ICGC datasets. Notably, patients with a low Cuscore had better prognoses and were more likely to benefit from immunotherapy.Additionally, the high Cuscore group in HCC also revealed three potential therapeutic targets (TUBA1B, CDC25B, and CSNK2A1) as well as several therapeutic compounds. Moreover, the experiment measured the expression levels of six prognosis-related CAGs, wherein knockdown of MTF1 exhibited suppression of proliferation, invasion, and migration formation in HCC cell lines. CONCLUSION: The findings have enhanced our comprehension of the cuproptosis characteristics in HCC, and stratification based on CuScore may potentially enhance the prediction of patients' prognosis and facilitate the development of effective and innovative treatment strategies.

Automatic MTF Conversion between Different Characteristics Caused by Imaging Devices.

Depending on various design conditions, including optics and circuit design, the image-forming characteristics of the modulated transfer function (MTF), which affect the spatial resolution of a digital image, may vary among image channels within or between imaging devices. In this study, we propose a method for automatically converting the MTF to the target MTF, focusing on adjusting the MTF characteristics that affect the signals of different image channels within and between different image devices. The experimental results of MTF conversion using the proposed method for multiple image channels with different MTF characteristics indicated that the proposed method could produce sharper images by moving the source MTF of each channel closer to a target MTF with a higher MTF value. This study is expected to contribute to technological advancements in various imaging devices as follows: (1) Even if the imaging characteristics of the hardware are unknown, the MTF can be converted to the target MTF using the image after it is captured. (2) As any MTF can be converted into a target, image simulation for conversion to a different MTF is possible. (3) It is possible to generate high-definition images, thereby meeting the requirements of various industrial and research fields in which high-definition images are required.

Intra-Observer and Inter-Observer Variability of Intraocular Lens Measurements Using an Interferometry Metrology Device.

The NIMO TEMPO (Lambda-X, Nivelles, Belgium) is a novel, user-friendly and compact device designed for in vitro optical analysis of refractive and diffractive intraocular lenses (IOLs). This device analyzes the IOL wavefront and generates a synthetic eye model for numerical computation. The objective of this study was to evaluate the precision of this innovative device. Intra- and inter-observer variability were calculated using a two-way analysis of variance (ANOVA) after conducting ten measurements of eight different IOL models, with each measurement being repeated by three distinct operators (resulting in a total of 30 measurements for each IOL). The device demonstrated satisfactory intra- and inter-observer variability in evaluating IOL power and modulation transfer function (MTF) profiles, with values of 0.066 and 0.078 diopters for IOL power and 0.018 and 0.019 for MTF measurements, respectively. Furthermore, this hybrid optical and numerical in vitro IOL wavefront analyzer appears to have several advantages over conventional optical bench devices. It reduces the need for operator manipulation, and allows for numerical modeling of various optical environments, including cornea models and apertures. In conclusion, this novel metrology device designed for refractive and diffractive IOLs appears to provide a satisfactory precision, making it a promising tool in the field of IOL metrology.

Ferroptosis-related gene MTF-1 as a novel prognostic biomarker in low-grade glioma and its correlation with immune infiltration.

Background: Metal-responsive transcription factor-1 performs a necessary position in a range of cancers. It is unknown, though, how the prognosis of patients with low-grade gliomas is related to immune infiltration. Method: The Cancer Genome Atlas database was used in this investigation to evaluate MTF-1 transcription in low-grade glioma and healthy brain tissues, and immunohistochemistry was used to confirm MTF-1 levels. By using functional enrichment analysis and R software, the putative biological roles and signaling pathways connected to MTF-1 in LGG as well as its prognostic significance were investigated. Further research was done on the connection involving MTF-1 and tumor mutational burden in LGG. Finally, the research evaluated how MTF-1 and immune cell infiltration are related. Results: We noticed that the WHO grade, 1p/19q codeletion, and older age were all substantially linked with MTF-1 overexpression in low-grade gliomas. OS and disease-specific survival were significantly lowered as a result of MTF-1 transcription. MTF-1 was recognized as an independent OS prognostic predictor with a poor prognosis by multifactorial Cox analysis. Functional enrichment analysis revealed that the primary enrichment pathways were chemical carcinogenesis-receptor activation and the generation of miRNAs implicated in gene suppression by miRNA. Additionally, there was a negative correlation between MTF-1 overexpression and the degree of immune cell infiltration in neutrophils and DC. Conclusion: MTF-1 may be a novel prognostic biomarker.

Tissue-Specific Tumour Suppressor and Oncogenic Activities of the Polycomb-like Protein MTF2.

The Polycomb repressive complex 2 (PRC2) is a conserved chromatin-remodelling complex that catalyses the trimethylation of histone H3 lysine 27 (H3K27me3), a mark associated with gene silencing. PRC2 regulates chromatin structure and gene expression during organismal and tissue development and tissue homeostasis in the adult. PRC2 core subunits are associated with various accessory proteins that modulate its function and recruitment to target genes. The multimeric composition of accessory proteins results in two distinct variant complexes of PRC2, PRC2.1 and PRC2.2. Metal response element-binding transcription factor 2 (MTF2) is one of the Polycomb-like proteins (PCLs) that forms the PRC2.1 complex. MTF2 is highly conserved, and as an accessory subunit of PRC2, it has important roles in embryonic stem cell self-renewal and differentiation, development, and cancer progression. Here, we review the impact of MTF2 in PRC2 complex assembly, catalytic activity, and spatiotemporal function. The emerging paradoxical evidence suggesting that MTF2 has divergent roles as either a tumour suppressor or an oncogene in different tissues merits further investigations. Altogether, our review illuminates the context-dependent roles of MTF2 in Polycomb group (PcG) protein-mediated epigenetic regulation. Its impact on disease paves the way for a deeper understanding of epigenetic regulation and novel therapeutic strategies.

Heterologous expression of mtf and mtc genes of Pseudanabaena foetida var. intermedia is sufficient to produce 2-methylisoborneol in Escherichia coli.

Microbial volatile metabolite 2-methylisoborneol (2-MIB) causes odor and taste issues in drinking water, making it unappealing for human consumption. It has been suggested that 2-MIB biosynthesis consists of two main steps, namely, methylation of geranyl diphosphate into 2-methyl geranyl diphosphate by geranyl diphosphate methyl transferase (GPPMT) and subsequent cyclization into 2-MIB by 2-MIB synthase (MIBS). Pseudanabaena foetida var. intermedia is a 2-MIB-producing cyanobacterium whose GPPMT and MIBS enzymes are encoded by adjacent mtf and mtc genes. The present study identified a 2-MIB-related gene cluster composed of cnbA, mtf, mtc, and cnbB genes in P. foetida var. intermedia. The two homologous cyclic nucleotide-binding protein genes, cnbA and cnbB, were detected adjacent to the mtf and mtc genes, respectively. The nucleotide sequence of the cnbA-mtf-mtc-cnbB gene cluster showed 99.55% identity with 2-MIB synthesis-associated gene cluster of Pseudanabaena sp. dqh15. RT-PCR results revealed that mtf and mtc genes are co-expressed, while cnbA and cnbB genes are expressed independently in P. foetida var. intermedia. To investigate whether only mtf and mtc genes are sufficient for 2-MIB synthesis, the two-gene unit (mtf-mtc) was introduced into Escherichia coli strain JM109 via overexpression vector pYS1C. Gas chromatograph-mass spectrometry results showed that the E. coli strain transformed with mtf-mtc was able to produce 2-MIB. The intracellular 2-MIB level in P. foetida var. intermedia was higher than the extracellular 2-MIB level, while the transformed E. coli strain showed an opposite trend. Growth inhibition was observed in the 2-MIB-producing transformed E. coli strain. IMPORTANCE Contamination of drinking water with odiferous microbial metabolite 2-MIB is a worldwide concern. Removal of 2-MIB from drinking water burdens the water purification process. Therefore, it is important to search for alternative methods, such as suppressing the production of 2-MIB by aquatic microorganisms. For that, it is necessary to expand the current knowledge about the mechanism of 2-MIB synthesis at the genetic level. This study revealed that mtf and mtc genes of the 2-MIB-related gene cluster are transcribed as a single unit in P. foetida var. intermedia, and the expression of both mtf and mtc genes is essential and sufficient for 2-MIB synthesis in E. coli heterologous gene expression system.

An intelligent diagnostic method of ECG signal based on Markov transition field and a ResNet.

BACKGROUND AND OBJECTIVE: Heart disease seriously threatens human life and health. It has the character of abruptness and is necessary to accurately monitor and intelligently diagnose electrocardiograph signals in real-time. As part of the automation of heart monitoring, the electrocardiogram (ECG) intelligent diagnosis method based on deep learning not only meets the needs of real-time and accurate but also can abandon relevant professional knowledge, which makes it possible to be promoted in the general population. METHODS: This paper presents an intelligent diagnosis method based on a ResNet. Firstly, ECG signals from MIT-BIH Database are converted into 2-dim matrices by Markov Transition Field. Secondly, the matrices are used as the input of a ResNet. Then, the ResNet is able to extract high abstract features of various diseases and realize intelligent identification of five heartbeat types, including Normal Beat, Left Bundle Branch Block Beat, Right Bundle Branch Block Beat, Premature Ventricular Contraction Beat, and Atrial Premature Contraction Beat. Eventually, the proposed model is used to identify Normal Beat and Atrial Fibrillation(AF) based on the PAF Prediction Challenge Database(the PAFPC Database) to verify its generalization ability. RESULTS: The experiment result shows that the intelligent diagnosis method can reach a high F1-score of 97.7% and a high accuracy upon to 99.2% on MIT-BIH Database, which are higher than the models proposed by other researchers. Its mean sensitivity and mean specificity are 97.42% and 99.54%, respectively. Moreover, the accuracy of the generalization ability verification experiment is 94.57% on the PAFPC Database, which is also higher than the results of other studies. CONCLUSION: The research results show that the method proposed in this paper still achieves higher accuracy and higher F1-score than other methods without any data preprocessing. This method has better classification performance than traditional machine learning methods and other deep learning methods. That is, the method based on Markov Transition Field and a ResNet has good application prospects. At the same time, it has been verified that the model proposed in this paper also has excellent generalization ability.

Exploration of the pulse pileup effects in a clinical CdTe-based photon-counting computed tomography.

BACKGROUND: High tube current generates a high flux of x-rays to photon counting detectors (PCDs) that can potentially result in the piling up of pulses formed by concurrent photons, which can cause count loss and energy resolution degradation. PURPOSE: To evaluate the performance of clinical photon-counting CT (PCCT) systems in high flux, potentially influenced by pulse pileup effects, in terms of task-generic image quality metrics. METHODS: A clinical phantom was scanned on a commercial PCCT scanner (NAEOTOM Alpha, Siemens) at 120 kV under fourteen different tube current levels (40-1000 mA) with a rotation time of 0.25 s and a pitch of 1. The dose levels corresponded to CTDIvol (32 cm phantom) of 0.79-19.8 mGy. CT sinograms were reconstructed using QIR-off mode (noniterative reconstruction algorithm), Br44 kernel, and a voxel size of 0.4102 × 0.4102 × 3 mm 3 $0.4102 \times 0.4102 \times 3{\mathrm{\ mm}}^3$ . imQuest, an open-source MATLAB-based software package was used to calculate noise power spectrum (NPS), task transfer function (TTF), contrast-to-noise ratio (CNR), and CT number according to AAPM Task Group 233 metrology. RESULTS: The 50% cut-off frequency of TTF (f50 ) remained mostly constant across all higher tube currents for all inserts, namely polyethylene, bone, air, and acrylic. Using the lowest two data points (40 and 80 mA), the expected relationship between noise magnitude and tube current was determined to be noise ∝ $ \propto \ $ mA-0.47 . The measured noise magnitude were up to 11.1% higher than the expected value at the highest tube current. The average frequency of NPS (fav ) decreased from 0.32 to 0.29 mm-1 as tube current increased from 40 to 1000 mA. No considerable effects were observed in CT number measurement of any insert; however, CT numbers for air and bone changed almost monotonically as tube current increased. Absolute CNR increased monotonically for all inserts; however, the difference between measured and expected CNRs were approximately -6% to 12% across all tube currents. CONCLUSIONS: Increasing tube currents did not affect the spatial resolution, but slightly affected the CT number and noise measurements of the clinical PCCT system. However, the effects were only considerable at clinically irrelevant tube currents used on a small 20-cm phantom. In general clinical practices, automatic exposure control techniques are used to decrease the variation of flux on the detector, which alleviates the chances of detector saturation due to high count rates. The observed effects could be due to pulse pileup, signal-dependent filtration of the system, or nonlinearities in the reconstruction algorithm. In conclusion, either the deadtime of the detector used in the photon-counting CT system is shorter such that count losses due to pulse pileup are negligible, or pulse pileup has inconsiderable effects on the image quality of clinical photon-counting CT systems in routine clinical practice due to possible corrections applied on the system.

Pb exposure causes non-linear accumulation of Pb in D. melanogaster controlled by metallothionein B and exerts ecological effects.

Pb pollution can harm human health and the ecosystem. Therefore, it is worthwhile to study the metabolic processes of heavy metals in individual bodies and their influence on ecological systems. In this work, we analyzed the genetic responses and physiological changes of D. melanogaster which took diets exposed to different doses of Pb using transcriptomic analysis, ICP-MS, and various other physiological methods. We found that the Pb accumulated in D. melanogaster in a nonlinear pattern with the increase of Pb content in food. Metallothioneins (Mtns), especially the MtnB directly affects the accumulation and excretion of metal Pb in D. melanogaster, and causes the nonlinear accumulation. Metal regulatory transcription factor-1 (MTF-1) is involved in the regulation of Pb-induced high expressions of Mtns. Furthermore, an interaction between the metal metabolism pathway and xenobiotic response pathway leads to the cross-tolerances of Pb-exposed D. melanogaster to insecticides and other toxins. The oxidative stress induced by Pb toxicity may be the bridge between them. Our findings provide a physiological and molecular genetic basis for further study of the accumulation and metabolism of Pb in D. melanogaster.

Human cells experience a Zn2+ pulse in early G1.

Zinc is an essential micronutrient required for all domains of life. Cells maintain zinc homeostasis using a network of transporters, buffers, and transcription factors. Zinc is required for mammalian cell proliferation, and zinc homeostasis is remodeled during the cell cycle, but whether labile zinc changes in naturally cycling cells has not been established. We use genetically encoded fluorescent reporters, long-term time-lapse imaging, and computational tools to track labile zinc over the cell cycle in response to changes in growth media zinc and knockdown of the zinc-regulatory transcription factor MTF-1. Cells experience a pulse of labile zinc in early G1, whose magnitude varies with zinc in growth media. Knockdown of MTF-1 increases labile zinc and the zinc pulse. Our results suggest that cells need a minimum zinc pulse to proliferate and that if labile zinc levels are too high, cells pause proliferation until labile cellular zinc is lowered.

The biological significance of cuproptosis-key gene MTF1 in pan-cancer and its inhibitory effects on ROS-mediated cell death of liver hepatocellular carcinoma.

Metal regulatory transcription factor 1 (MTF1) has been reported to be correlated with several human diseases, especially like cancers. Exploring the underlying mechanisms and biological functions of MTF1 could provide novel strategies for clinical diagnosis and therapy of cancers. In this study, we conducted the comprehensive analysis to evaluate the profiles of MTF1 in pan-cancer. For example, TIMER2.0, TNMplot and GEPIA2.0 were employed to analyze the expression values of MTF1 in pan-cancer. The methylation levels of MTF1 were evaluated via UALCAN and DiseaseMeth version 2.0 databases. The mutation profiles of MTF1 in pan-cancers were analyzed using cBioPortal. GEPIA2.0, Kaplan-Meier plotter and cBioPortal were also used to explore the roles of MTF1 in cancer prognosis. We found that high MTF1 expression was related to poor prognosis of liver hepatocellular carcinoma (LIHC) and brain lower grade glioma (LGG). Also, high expression level of MTF1 was associated with good prognosis of kidney renal clear cell carcinoma (KIRC), lung cancer, ovarian cancer and breast cancer. We investigated the genetic alteration and methylation levels of MTF1 between the primary tumor and normal tissues. The relationship between MTF1 expression and several immune cells was analyzed, including T cell CD8 + and dendritic cells (DC). Mechanically, MTF1-interacted molecules might participate in the regulation of metabolism-related pathways, such as peptidyl-serine phosphorylation, negative regulation of cellular amide metabolic process and peptidyl-threonine phosphorylation. Single cell sequencing indicated that MTF1 was associated with angiogenesis, DNA repair and cell invasion. In addition, in vitro experiment indicated knockdown of MTF1 resulted in the suppressed cell proliferation, increased reactive oxygen species (ROS) and promoted cell death in LIHC cells HepG2 and Huh7. Taken together, this pan-cancer analysis of MTF1 has implicated that MTF1 could play an essential role in the progression of various human cancers.

Characterization of a Timepix detector for use in SEM acceleration voltage range.

Hybrid pixel direct electron detectors are gaining popularity in electron microscopy due to their excellent properties. Some commercial cameras based on this technology are relatively affordable which makes them attractive tools for experimentation especially in combination with an SEM setup. To support this, a detector characterization (Modulation Transfer Function, Detective Quantum Efficiency) of an Advacam Minipix and Advacam Advapix detector in the 15-30 keV range was made. In the current work we present images of Point Spread Function, plots of MTF/DQE curves and values of DQE(0) for these detectors. At low beam currents, the silicon detector layer behaviour should be dominant, which could make these findings transferable to any other available detector based on either Medipix2, Timepix or Timepix3 provided the same detector layer is used.