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STUDY QUESTION: Can the density of the inner cell mass (ICM) be a new indicator of the quality of the human blastocyst? SUMMARY ANSWER: The densification index (DI) developed in this study can quantify ICM density and provide positive guidance for ploidy, pregnancy, and live birth. WHAT IS KNOWN ALREADY: In evaluating the quality of ICM, reproductive care clinics still use size indicators without further evaluation. The main disadvantage of this current method is that the evaluation of blastocyst ICM is relatively rough and cannot meet the needs of clinical embryologists, especially when multiple blastocysts have the same ICM score, which makes them difficult to evaluate further. STUDY DESIGN, SIZE, DURATION: This observational study included data from 2272 blastocysts in 1991 frozen-thawed embryo transfer (FET) cycles between January 2018 to November 2021 and 1105 blastocysts in 430 preimplantation genetic testing cycles between January 2019 and February 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: FET, ICSI, blastocyst culture, trophectoderm biopsy, time-lapse (TL) monitoring, and next-generation sequencing were performed. After preliminary sample size selection, the 11 focal plane images captured by the TL system were normalized and the spatial frequency was used to construct the DI of the ICM. MAIN RESULTS AND THE ROLE OF CHANCE: This study successfully constructed a quantitative indicator DI that can reflect the degree of ICM density in terms of fusion and texture features. The higher the DI value, the better the density of the blastocyst ICM, and the higher the chances that the blastocyst was euploid (P < 0.001) and that pregnancy (P < 0.001) and live birth (P = 0.005) were reached. In blastocysts with ICM graded B and blastocysts graded 4BB, DI was also positively associated with ploidy, pregnancy, and live birth (P < 0.05). ROC analysis showed that combining the Gardner scoring system with DI can more effectively predict pregnancy and live births, when compared to using the Gardner scoring system alone. LIMITATIONS, REASONS FOR CAUTION: Accurate calculation of the DI value places high demands on image quality, requiring manual selection of the clearest focal plane and exposure control. Images with the ICM not completely within the field of view cannot be used. The association between the density of ICM and chromosomal mosaicism was not evaluated. The associations between the density of ICM and different assisted reproductive technologies and different culture conditions in embryo laboratories were also not evaluated. Prospective studies are needed to further investigate the impact of ICM density on clinical outcomes. WIDER IMPLICATIONS OF THE FINDINGS: ICM density assessment is a new direction in blastocyst assessment. This study explores new ways of assessing blastocyst ICM density and develops quantitative indicators and a corresponding qualitative evaluation scheme for ICM density. The DI of the blastocyst ICM developed in this study is easy to calculate and requires only TL equipment and image processing, providing positive guidance for clinical outcomes. The qualitative evaluation scheme of ICM density can assist embryologists without TL equipment to manually evaluate ICM density. ICM density is a simple indicator that can be used in practice and is a good complement to the blastocyst scoring systems currently used in most centers. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research & Development Program of China (2021YFC2700603). The authors report no financial or commercial conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.
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BACKGROUND: To provide reference for clinical development of ADCs in the industry, we analyzed the landscape and characteristics of clinical trials about antibody-drug conjugates (ADCs). METHOD: Clinical trials to study ADCs used for the pharmacotherapy of cancers initiated by the sponsor were searched in the Cite line Pharma Intelligence (Trialtrove database), and the landscape and characteristics of these clinical trials were analyzed from multiple perspectives, such as the number, phases, status, indications, and targets of the clinical trials. RESULT: As of December 31, 2022, a total of 431 clinical trials have been initiated to study ADCs used for the pharmacotherapy of cancers, and the number of the last 10 years was 5.5 times as large as the first 11 years. These clinical trials involved 47 indications, including breast cancer, lymphoma (lymphoma, non-Hodgkin's and lymphoma, Hodgkin's), unspecified solid tumor, bladder cancer and lung cancer (lung, non-small cell cancer and lung, small cell cancer). As for each of these five indications, 50 + clinical trials have been carried out, accounting for as high as 48.50% (454/936). ADCs involve 38 targets, which are relatively concentrated. Among them, ERBB2 (HER2) and TNFRSF8 (CD30) involve in 100 + registered clinical trials, and TNFRSF17 (BCMA), NECTIN4 and CD19 in 10 + trials. The clinical trials for these five targets account for 79.02% (354/448) of the total number. Up to 93.97% (405/431) of these clinical trials explored the correlation between biomarkers and efficacy. Up to 45.91% (292/636) of Lots (lines of treatment) applied in the clinical trials were the second line. Until December 31, 2022, 54.52% (235/431) of the clinical trials have been completed or terminated. CONCLUSION: ADCs are a hotspot of research and development in oncology clinical trials, but the indications, targets, phases, and Lot that have been registered are seemingly relatively concentrated at present. This study provides a comprehensive analysis which can assist researchers/developer quickly grasp relevant knowledge to assess a product and also providing new clues and ideas for future research.
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Ensaios Clínicos como Assunto , Desenvolvimento de Medicamentos , Imunoconjugados , Neoplasias , Sistema de Registros , Humanos , Neoplasias/tratamento farmacológico , Imunoconjugados/uso terapêutico , Antineoplásicos/uso terapêuticoRESUMO
OBJECTIVES: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. METHODS: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). RESULTS: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.
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Epilepsia Resistente a Medicamentos , Epilepsia , Hemisferectomia , Espasmos Infantis , Criança , Humanos , Hemisferectomia/métodos , Espasmos Infantis/cirurgia , Estudos Retrospectivos , Fluordesoxiglucose F18 , Resultado do Tratamento , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Convulsões/diagnóstico , Convulsões/etiologia , Convulsões/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Imageamento por Ressonância Magnética , EletroencefalografiaRESUMO
In this paper, the bubble nucleation process of water was studied by molecular dynamics (MD) simulation. The nucleation mechanism of water on a grooved substrate was revealed from the perspective of hydrogen bond and energy change, and the effect of system pressure on nucleation was studied. The results show that the process of bubble nucleation of water molecules is essentially a process in which the thermal motion of water molecules gradually intensifies and the hydrogen bond continues to break with the increase in kinetic energy. As the hydrogen bond breaks, the kinetic energy of the water molecules is continuously converted to intermolecular potential energy. By analyzing the composition of the hydrogen bond energy, it is found that the electrostatic energy is much greater than the van der Waals energy, so the water nucleation process mainly overcomes the electrostatic force between molecules. With the gradual increase of pressure, although the kinetic energy distribution of molecules does not change significantly, it will cause the potential energy of water molecules to decrease significantly and then lead to the increase of the energy barrier that needs to be crossed for nucleation. Meanwhile, the rise of the nucleation barrier may result in the absence of obvious initial vapor nuclei inside the liquid so that the number of hydrogen bonds cannot be rapidly reduced, which is not conducive to boiling nucleation. The results of this study provide important implications for further understanding of the nucleate boiling process of water.
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The benchmark advanced oxidation technology (AOT) that uses UV/H2O2 integrated with hypochlorous species exhibits great potential in removing micropollutants and enhancing wastewater treatability for reclamation purposes. Although efforts have been made to study the reactions of H2O2 with hypochlorous species, there exist great discrepancies in the order of reaction kinetics, the rate constants, and the molecule-level mechanisms. This results in an excessive use of hypochlorous reagents and system underperformance during treatment processes. Herein, the titled reaction was investigated systematically through complementary experimental and theoretical approaches. Stopped-flow spectroscopic measurements revealed a combination of bi- and trimolecular reaction kinetics. The bimolecular pathway dominates at low H2O2 concentrations, while the trimolecular pathway dominates at high H2O2 concentrations. Both reactions were simulated using direct dynamics trajectories, and the pathways identified in the trajectories were further validated by high-level quantum chemistry calculations. The theoretical results not only supported the spectroscopic data but also elucidated the molecule-level mechanisms and helped to address the origin of the discrepancies. In addition, the impact of the environmental matrix was evaluated by using two waters with discrete characteristics, namely municipal wastewater and ammonium-rich wastewater. Municipal wastewater had a negligible matrix effect on the reaction kinetics of H2O2 and the hypochlorous species, making it a highly suitable candidate for this integration technique. The obtained in-depth reaction mechanistic insights will enable the development of a viable and economical technology for safe water reuse.
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Poluentes Químicos da Água , Purificação da Água , Águas Residuárias , Peróxido de Hidrogênio/química , Purificação da Água/métodos , Raios Ultravioleta , Poluentes Químicos da Água/análise , OxirreduçãoRESUMO
The formation and fragmentation of negatively charged 2-hydroxyethylhydrazinium nitrate ([HOCH2CH2NH2NH2]+NO3-, HEHN) ionic liquid clusters were examined using a guided-ion beam tandem mass spectrometer furnished with collision-induced dissociation of selected ions with Xe atoms. Measurements included the compositions of cluster ions formed in the ionization source, and the dissociation products, cross sections, and 0 K threshold energies for individually selected cluster ions. To identify the structures of the main cluster ion series [(HEHN)n(HNO3)0-1NO3]- formed, molecular dynamics simulations were employed to create initial geometry guesses, followed by optimization at the ωB97XD/6-31+G(d,p) level of theory, from which global minimum structures were identified for reaction thermodynamics analyses. A comparison was made between the cluster formation and fragmentation in the negatively charged 2-hydroxyethylhydrazinium nitrate with those in the positive mode (reported by W. Zhou et al., Phys. Chem. Chem. Phys., 2023, 25, 17370). In both modes, the cluster ions were predominantly composed of m/z below 350; loss of a neutral 2-hydroxyethylhydrazinium nitrate ion pair represents the most important cluster fragmentation pathway, followed by intra-ion pair proton transfer-mediated 2-hydroxyethylhydrazine and HNO3 elimination; and all clusters started to dissociate at threshold energies less than 1.5 eV. The overwhelming similarities in the formation and fragmentation chemistry of positively vs. negatively charged 2-hydroxyethylhydrazinium nitrate clusters may be attributed to their inherent ionic nature and high electric conductivities.
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Skin is the most prominent tissue and organ, as well as the first line of defence, of the body. Because it is situated on the body's surface, it is constantly exposed to microbial, chemical, and physical factors such as mechanical stimulation. Therefore, skin has evolved substantial immune defences, regenerative ability, and anti-injury capacity. Epidermal cells produce antibacterial peptides that play a role in immune defence under physiological conditions. Additionally, IgG or IgA in the skin also participates in local anti-infective immunity. However, based on the classical theory of immunology, Ig can only be produced by B cells which should be derived from local B cells. This year, thanks to the discovery of Ig derived from non B cells (non B-Ig), Ig has also been found to be expressed in epidermal cells and contributes to immune defence. Epidermal cell-derived IgG and IgA have been demonstrated to have potential antibody activity by binding to pathogens. However, these epidermal cell-derived Igs show different microbial binding characteristics. For instance, IgG binds to Staphylococcus aureus and IgA binds to Staphylococcus epidermidis. Epidermal cells producing IgG and IgA may serve as an effective defense mechanism alongside B cells, providing a novel insight into skin immunity.
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Imunoglobulina A , Pele , Humanos , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Pele/imunologia , Animais , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Linfócitos B/imunologia , Imunoglobulinas/imunologia , Imunoglobulinas/metabolismo , Staphylococcus aureus/imunologia , Staphylococcus epidermidis/imunologia , Epiderme/imunologia , Epiderme/metabolismo , Células Epidérmicas/imunologia , Células Epidérmicas/metabolismoRESUMO
Humans have an extraordinary ability to recognize and differentiate voices. It is yet unclear whether voices are uniquely processed in the human brain. To explore the underlying neural mechanisms of voice processing, we recorded electrocorticographic signals from intracranial electrodes in epilepsy patients while they listened to six different categories of voice and nonvoice sounds. Subregions in the temporal lobe exhibited preferences for distinct voice stimuli, which were defined as "voice patches." Latency analyses suggested a dual hierarchical organization of the voice patches. We also found that voice patches were functionally connected under both task-engaged and resting states. Furthermore, the left motor areas were coactivated and correlated with the temporal voice patches during the sound-listening task. Taken together, this work reveals hierarchical cortical networks in the human brain for processing human voices.
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Percepção Auditiva/fisiologia , Encéfalo/fisiologia , Vias Neurais/fisiologia , Voz/fisiologia , Adulto , Eletrocorticografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Mitochondria are essential for maintaining skeletal muscle metabolic homeostasis during adaptive response to a myriad of physiologic or pathophysiological stresses. The mechanisms by which mitochondrial function and contractile fiber type are concordantly regulated to ensure muscle function remain poorly understood. Evidence is emerging that the Folliculin interacting protein 1 (Fnip1) is involved in skeletal muscle fiber type specification, function, and disease. In this study, Fnip1 was specifically expressed in skeletal muscle in Fnip1-transgenic (Fnip1Tg) mice. Fnip1Tg mice were crossed with Fnip1-knockout (Fnip1KO) mice to generate Fnip1TgKO mice expressing Fnip1 only in skeletal muscle but not in other tissues. Our results indicate that, in addition to the known role in type I fiber program, FNIP1 exerts control upon muscle mitochondrial oxidative program through AMPK signaling. Indeed, basal levels of FNIP1 are sufficient to inhibit AMPK but not mTORC1 activity in skeletal muscle cells. Gain-of-function and loss-of-function strategies in mice, together with assessment of primary muscle cells, demonstrated that skeletal muscle mitochondrial program is suppressed via the inhibitory actions of FNIP1 on AMPK. Surprisingly, the FNIP1 actions on type I fiber program is independent of AMPK and its downstream PGC-1α. These studies provide a vital framework for understanding the intrinsic role of FNIP1 as a crucial factor in the concerted regulation of mitochondrial function and muscle fiber type that determine muscle fitness.
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Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Mitocôndrias Musculares/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Animais , Feminino , Perfilação da Expressão Gênica , Masculino , Camundongos , Camundongos Transgênicos , Mitocôndrias Musculares/ultraestrutura , Fibras Musculares Esqueléticas/ultraestrutura , Especificidade de Órgãos , Oxirredução , Estresse OxidativoRESUMO
Background: Plasma exchange is the most commonly applied method for treating severe hepatitis. As a kind of invasive treatment, plasma exchange may have various complications during treatment. Therefore, effective nursing should be implemented during plasma exchange treatment to prevent the incidence of complications. Objective: To compare the effects of traditional nursing methods versus evidence-based nursing practices on the quality of life and anxiety of patients with liver injury. Design: This was a retrospective study. Patient data were obtained from patient records. Setting: This study was carried out in the Department of Gastroenterology, Second Hospital of Hebei Medical University. Participants: One hundred and twenty severe hepatitis patients with 89 cases of early hepatic failure and 31 cases of middle hepatic failure admitted to our department from January 2020 to December 2022 were chosen, followed by randomly separating into a control group and an observation group. Interventions: The control group adopted nursing, while the observation group received evidence-based nursing including psychological nursing, nursing during treatment and post-treatment nursing. Primary Outcome Measures: (1) liver function (2) emotional state assessed by Self-rating Anxiety Scale (SAS) along with Self-rating Depression Scale (SDS) (3) coagulation function, (4) quality of life assessed by Short-Form 36 (SF-36) scale (5) nursing satisfaction, and (6) incidence of complications. Results: In contrast to the control group, the occurrence of complications in the observation group was significantly lower (P < .05). At 1-month review, the quality of life score in the observation group was higher in contrast to the control group (P < .05). In contrast to the control group, the nursing satisfaction of patients in the observation group was better (P < .05), alanine aminotransferase and total bilirubin levels in the observation group were lower, while albumin levels were higher (P < .05), the anxiety and depression scores of the observation group were lessened (P < .05), and the required time of coagulation function indexes in the observation group was shorter (P < .05). Conclusion: The application of evidence-based nursing to artificial liver therapy in patients with liver failure can effectively promote the liver function and coagulation index of patients, help to relieve negative emotions, and promote the quality of life of patients. This study may provide clinical reference for the nursing of artificial liver therapy in patients with liver failure.
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To solve the problem of aperture fill time (AFT) for wideband sparse arrays, variable fractional delay (VFD) FIR filters are applied to eliminate linear coupling between spatial and time domains. However, the large dimensions of the filter coefficient matrix result in high system complexity. To alleviate the computational burden of solving VFD filter coefficients, a novel multi-regultion minimax (MRMM) model utilizing the sparse representation technique has been presented. The error function is constrained by the introduction of L2-norm and L1-norm regularizations within the minimax criterion. The L2-norm effectively resolves the problems of overfitting and non-unique solutions that arise in the sparse optimization of traditional minimax (MM) models. Meanwhile, the use of multiple L1-norms enables the optimal design of the smallest sub-filter number and order of the VFD filter. To solve the established nonconvex model, an improved sequential-alternating direction method of multipliers (S-ADMM) algorithm for filter coefficients is proposed, which utilizes sequential alternation to iteratively update multiple soft-thresholding problems. The experimental results show that the optimized VFD filter reduces system complexity significantly and corrects AFT effectively in a wideband sparse array.
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Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.
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Glicosídeos , Picrorhiza , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Linhagem Celular Tumoral , Picrorhiza/química , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Medicamentos de Ervas Chinesas/química , TriterpenosRESUMO
Age prediction is an important field in forensic and aging research. Traditional methods used DNA methylation, telomere shortening, and mitochondrial DNA mutations to conduct age prediction models. Sex chromosomes, like the Y chromosome, have a significant role in aging as previously reported in hematopoietic disease and many non-reproductive cancers. Until now, there is no age predictor based on the percentage of loss of Y chromosome (LOY). LOY has been previously revealed to be correlated with Alzheimer's disease, short survival, and higher risk of cancer. The possible correlation of LOY between normal aging was not fully explored. In this study, we conducted age prediction by measuring LOY percentage by droplet digital PCR (ddPCR), based on 232 healthy male samples, including 171 blood samples, 49 saliva samples, 12 semen samples. The age group of samples ranges from 0 to 99 years, with two individuals in almost every single age. Pearson correlation method was performed to calculate the correlation index. The result indicated a correlation index of 0.21 (p = 0.0059) between age and LOY percentage in blood samples, with the regression formula being y = - 0.016823 + 0.001098x. The correlation between LOY percentage and age is obvious only when the individuals were divided into different age groups (R = 0.73, p = 0.016). In the studied saliva and semen samples, p-values of the correlation are 0.11 and 0.20, respectively, showing no significant association between age and LOY percentage in these two biological materials. For the first time, we investigated male-specific age predictor based on LOY. The study showed that LOY in leukocytes can be regarded as a male-specific age predictor for age group estimation in forensic genetics. This study might be indicative for forensic applications and aging research.
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Genética Forense , Neoplasias , Humanos , Masculino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Y/genética , Leucócitos , Envelhecimento/genética , Neoplasias/genéticaRESUMO
Isocitrate dehydrogenase (IDH) mutations are common genetic alterations in myeloid disorders, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Epigenetic changes, including abnormal histone and DNA methylation, have been implicated in the pathogenic build-up of hematopoietic progenitors, but it is still unclear whether and how IDH mutations themselves affect hematopoiesis. Here, we show that IDH1-mutant mice develop myeloid dysplasia in that these animals exhibit anemia, ineffective erythropoiesis, and increased immature progenitors and erythroblasts. In erythroid cells of these mice, D-2-hydroxyglutarate, an aberrant metabolite produced by the mutant IDH1 enzyme, inhibits oxoglutarate dehydrogenase activity and diminishes succinyl-coenzyme A (CoA) production. This succinyl-CoA deficiency attenuates heme biosynthesis in IDH1-mutant hematopoietic cells, thus blocking erythroid differentiation at the late erythroblast stage and the erythroid commitment of hematopoietic stem cells, while the exogenous succinyl-CoA or 5-ALA rescues erythropoiesis in IDH1-mutant erythroid cells. Heme deficiency also impairs heme oxygenase-1 expression, which reduces levels of important heme catabolites such as biliverdin and bilirubin. These deficits result in accumulation of excessive reactive oxygen species that induce the cell death of IDH1-mutant erythroid cells. Our results clearly show the essential role of IDH1 in normal erythropoiesis and describe how its mutation leads to myeloid disorders. These data thus have important implications for the devising of new treatments for IDH-mutant tumors.
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Eritropoese/genética , Células-Tronco Hematopoéticas/metabolismo , Heme/biossíntese , Isocitrato Desidrogenase/genética , Mutação de Sentido Incorreto , Mutação Puntual , Pré-Leucemia/genética , Acil Coenzima A/biossíntese , Acil Coenzima A/deficiência , Anemia/genética , Animais , Medula Óssea/patologia , Eritroblastos/metabolismo , Técnicas de Introdução de Genes , Glutaratos/metabolismo , Heme/deficiência , Heme Oxigenase-1/metabolismo , Isocitrato Desidrogenase/fisiologia , Complexo Cetoglutarato Desidrogenase/antagonistas & inibidores , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/patologia , Mielopoese/genética , Pré-Leucemia/metabolismo , Pré-Leucemia/patologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes/metabolismo , Esplenomegalia/etiologia , Trombocitopenia/genéticaRESUMO
We proposed a numerical and accurate quadratic phase aberration compensation method in digital holography. A phase imitation method based on Gaussian 1σ-criterion is used to obtain the morphological features of the object phase using partial differential, filtering and integration successively. We also propose an adaptive compensation method based on a maximum-minimum-average- α-standard deviation (MMAαSD) evaluation metric to obtain optimal compensated coefficients by minimizing the above metric of the compensation function. The effectiveness and robustness of our method are demonstrated by simulation and experiments.
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A system and method for non-destructive detection of cracks of different width and depths based on digital speckle interferometry coupled with pulsed laser excitation is introduced and tested. Based on photoacoustic effect, acoustic waves are induced onto the rear of the samples by pumping a pulsed laser beam on it. The generated mechanical wave propagates from the rear surface of the sample to the front while front surface is monitored by speckle interferometry. In order to acquire information about surface deformation, the front surface is illuminated by continuous wave laser and interference are imaged onto the camera as speckle images. After processing the produced fringe patterns, it indicates the presence and location of the cracks in qualitative way. In this study, the system and method mentioned above are validated by detecting medium density fiberboard with simulated cracks. The fringe patterns from areas with or without defects are compared and discussed. Besides, the system and method to distinguish and predict cracks sizes is proposed and validated.
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We propose a numerical and automatic quadratic phase aberration elimination method in digital holography for phase-contrast imaging. A histogram segmentation method based on Gaussian 1σ-criterion is used to obtain the accurate coefficients of quadratic aberrations using the weighted least-squares algorithm. This method needs no manual intervention for specimen-free zone or prior parameters of optical components. We also propose a maximum-minimum-average-standard deviation (MMASD) metric to quantitatively evaluate the effectiveness of quadratic aberration elimination. Simulation and experimental results are demonstrated to verify the efficacy of our proposed method over the traditional least-squares algorithm.
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Cr(VI) detoxification and organic matter (OM) stabilization are usually influenced by the biological transformation of iron (Fe) minerals; however, the underlying mechanisms of metal-reducing bacteria on the coupled kinetics of Fe minerals, Cr, and OM remain unclear. Here, the reductive sequestration of Cr(VI) and immobilization of fulvic acid (FA) during the microbially mediated phase transformation of ferrihydrite with varying Cr/Fe ratios were investigated. No phase transformation occurred until Cr(VI) was completely reduced, and the ferrihydrite transformation rate decreased as the Cr/Fe ratio increased. Microscopic analysis was uncovered, which revealed that the resulting Cr(III) was incorporated into the lattice structure of magnetite and goethite, whereas OM was mainly adsorbed on goethite and magnetite surfaces and located within pore spaces. Fine line scan profiles showed that OM adsorbed on the Fe mineral surface had a lower oxidation state than that within nanopores, and C adsorbed on the magnetite surface had the highest oxidation state. During reductive transformation, the immobilization of FA by Fe minerals was predominantly via surface complexation, and OM with highly aromatic and unsaturated structures and low H/C ratios was easily adsorbed by Fe minerals or decomposed by bacteria, whereas Cr/Fe ratios had little effect on the binding of Fe minerals and OM and the variations in OM components. Owing to the inhibition of crystalline Fe minerals and nanopore formation in the presence of Cr, Cr sequestration and C immobilization can be synchronously favored at low Cr/Fe ratios. These findings provide a profound theoretical basis for Cr detoxification and synchronous sequestration of Cr and C in anoxic soils and sediments.
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Óxido Ferroso-Férrico , Minerais , Minerais/química , Compostos Férricos/química , Cromo/química , OxirreduçãoRESUMO
BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) and advanced hepatic fibrosis (AHF) have been associated with sarcopenia. However, modifiers of this association have been less studied. METHODS: This study used data from the NHANES database 2011-2014 of the USA. Adults aged 18 years or older, had complete information of handgrip strength test and NAFLD and AHF status were eligible for inclusion. NAFLD was defined using the Fatty Liver Index (FLI). AHF was defined using the NAFLD fibrosis score (NFS). Univariate and multivariate logistic regression were performed to determine the associations between the study variables and prevalent NAFLD and AHF. RESULTS: A total of 19 931 participants were selected from the 2011-2014 NHANES database. The multivariate analysis showed that stronger grip strength was significantly and independently associated with decreased odds for NAFLD (tertile 2: adjusted odd ratio [aOR]: 0.41, 95% confidence interval [CI]: 0.29-0.59; tertile 3: aOR: 0.11, 95% CI: 0.05-0.24) and AHF (tertile 2: aOR: 0.66, 95% CI: 0.46-0.94; tertile 3: aOR: 0.28, 95% CI: 0.12-0.63). In stratified analyses, strongest grip strength was significantly associated with reduced odds for NAFLD regardless of age, body mass index, and having diabetes or not. Strongest grip strength was associated with reduced odds for NAFLD in individuals who had moderate to ideal physical activity (aOR: 0.31). CONCLUSIONS: Grip strength has an inverse association with prevalent NAFLD and AHF in the US population, which appears to be modified by physical activity level. Future prospective cohort studies are needed to clarify the role of physical activity in modifying the risks.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Inquéritos Nutricionais , Força da Mão , Estudos Transversais , Prevalência , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicaçõesRESUMO
The 2-hydroxyethylhydrazinium nitrate ([HOCH2CH2NH2NH2]+NO3-, HEHN) ionic liquid has the potential to power both electric and chemical thrusters and provide a wider range of specific impulse needs. To characterize its capabilities as an electrospray propellant, we report the formation of HEHN cluster ions in positive electrospray ionization (ESI) and their collision-induced dissociation. The experiment was carried out using ESI guided-ion beam mass spectrometry which mimics an electrospray thruster in terms of ion emission, injection into a vacuum and fragmentation in space. Measurements include compositions of primary ions in the electrospray plume and their individual dissociation product ion cross sections and threshold energies. The results were interpreted in light of theoretical modeling. To determine cluster structures that are comprised of [HE + H]+ and NO3- constituents, classical mechanics simulations were used to create initial guesses; and for clusters that are formed by reactions between ionic constituents, quasi-classical direct dynamics trajectory simulations were used to mimic covalent bond formation and structures. All candidate structures were subject to density functional theory optimization, from which global minimum structures were identified and used for construction of reaction potential energy surface. The comparison between experimental values and calculated dissociation thermodynamics was used to verify the structures for the emitted species [(HEHN)nHE + H]+, [(HEHN)n(HE)2 + H]+, [(HE)n+1 + H]+ and [(HE)nC2H4OH]+ (n = 0-2), of which [(HE)1-2 + H]+ dominates. Due to the protic nature of HEHN, cluster fragmentation can be rationalized by proton transfer-mediated elimination of HNO3, HE and HE·HNO3, and the latter two become dominant in larger clusters. [(HE)2 + H]+ and [(HE)nC2H4OH]+ contain H-bonded water and consequently are featured by water elimination in fragmentation. These findings help to evaluate ion formation and fragmentation efficiencies and their impacts on electrospray propulsion.