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[This corrects the article DOI: 10.1016/j.heliyon.2024.e24798.].
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This study takes the parent-child game behavior of children aged 3~6 and their parents as the research object, and extracts and summarizes the user behavioral needs of parents and children when they use game-based furniture together by using the questionnaire research method, observation method, and interview method. Based on the KJ method, 16 behavioral demand indicators were compiled by five furniture design students to construct a user behavioral demand system. In addition, AHP and entropy weight method were used to solve the user behavioral demand weights from subjective and objective perspectives in this study. Twenty experts and designers in this research field scored the indicators two by two and solved the subjective weights of user behavioral requirements according to the AHP algorithm. A seven-level Likert scale was used to design the questionnaire and distribute it to the parents of children aged 3-6 to fill in, and the 121 valid questionnaires obtained were used as raw data for entropy weighting to obtain the objective weights of user behavioral needs representing the opinions of interactive game-based furniture users. Finally, with 0.4 as the proportion coefficient of subjective weights, the subjective and objective weights were weighted to get the comprehensive weight value of each demand. The results show that the eight items with higher weights for user behavioral needs include: firm and stable, safe in use, comfortable for both parents and children, holding behavior by human-machine dimensions, able to sit on the ground and play, able to play face-to-face, easy to find for picking up, and sufficient operating space. In general, parent-child interactive game furniture firstly needs to meet the user's needs for safety and comfort, and secondly needs to meet the user's needs for the state of the game posture and the furniture size to meet the needs of the fetching and storage posture and the game space. The fuzzy comprehensive evaluation model established based on these needs can take into account the opinions of design experts and users at the same time and put the needs of children and parents in an equally important position so that the design of children's play furniture can tend to meet the needs of parents and children when they use it together, and to promote parent-child interaction and the healthy growth of children.
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Diseño Interior y Mobiliario , Humanos , Niño , Preescolar , Masculino , Encuestas y Cuestionarios , Femenino , Relaciones Padres-Hijo , Padres/psicología , Juegos de Video , Conducta Infantil/psicología , Adulto , Diseño de EquipoRESUMEN
The commitment and differentiation of human placental progenitor cytotrophoblast (CT) cells are crucial for a successful pregnancy, but the underlying mechanism remains poorly understood. Here, we identified the transcription factor (TF), specificity protein 6 (SP6), as a human species-specific trophoblast lineage TF expressed in human placental CT cells. Using pluripotent stem cells as a model, we demonstrated that SP6 controls CT generation and the establishment of trophoblast stem cells (TSCs) and identified msh homeobox 2 (MSX2) as the downstream effector in these events. Mechanistically, we showed that SP6 interacts with histone acetyltransferase P300 to alter the landscape of H3K27ac at targeted regulatory elements, thereby favoring transcriptional activation and facilitating CT cell fate decisions and TSC maintenance. Our results established SP6 as a regulator of the human trophoblast lineage and implied its role in placental development and the pathogenies of placental diseases.
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Diferenciación Celular , Proteínas de Homeodominio , Trofoblastos , Humanos , Trofoblastos/metabolismo , Trofoblastos/citología , Femenino , Proteínas de Homeodominio/metabolismo , Proteínas de Homeodominio/genética , Embarazo , Placenta/metabolismo , Placenta/citología , Linaje de la Célula , Placentación , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Células Madre/metabolismo , Células Madre/citología , Secuencias Reguladoras de Ácidos Nucleicos/genética , Células Madre Pluripotentes/metabolismo , Células Madre Pluripotentes/citologíaRESUMEN
Cardiac injury plays a critical role in the process of thoracic trauma-related fatal outcomes. Historically, most patients who suffer a cardiac rupture typically die at the scene of occurrence or in the hospital, despite prompt medical intervention. Delayed cardiac rupture, although rare, may occur days after the initial injury and cause sudden unexpected death. Herein, we present the clinical details of a young man who suffered a chest stab injury and recovered well initially, but died days later due to delayed cardiac rupture. The forensic autopsy confirmed delayed cardiac rupture as the cause of death. We also reviewed previous similar reports to provide suggestions in such rare cases in clinical and forensic practice.
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Pigs share anatomical and physiological traits with humans and can serve as a large-animal model for translational medicine. Bona fide porcine pluripotent stem cells (PSCs) could facilitate testing cell and drug therapies. Agriculture and biotechnology may benefit from the ability to produce immune cells for studying animal infectious diseases and to readily edit the porcine genome in stem cells. Isolating porcine PSCs from preimplantation embryos has been intensively attempted over the past decades. We previously reported the derivation of expanded potential stem cells (EPSCs) from preimplantation embryos and by reprogramming somatic cells of multiple mammalian species, including pigs. Porcine EPSCs (pEPSCs) self-renew indefinitely, differentiate into embryonic and extra-embryonic lineages, and permit precision genome editing. Here we present a highly reproducible experimental procedure and data of an optimized and robust porcine EPSC culture system and its use in deriving new pEPSC lines from preimplantation embryos and reprogrammed somatic cells. No particular expertise is required for the protocols, which take ~4-6 weeks to complete. Importantly, we successfully established pEPSC lines from both in vitro fertilized and somatic cell nuclear transfer-derived embryos. These new pEPSC lines proliferated robustly over long-term passaging and were amenable to both simple indels and precision genome editing, with up to 100% targeting efficiency. The pEPSCs differentiated into embryonic cell lineages in vitro and teratomas in vivo, and into porcine trophoblast stem cells in human trophoblast stem cell medium. We show here that pEPSCs have unique epigenetic features, particularly H3K27me3 levels substantially lower than fibroblasts.
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Blastocisto , Reprogramación Celular , Animales , Blastocisto/citología , Porcinos , Técnicas de Cultivo de Célula/métodos , Diferenciación Celular , Células Madre Pluripotentes/citología , FemeninoRESUMEN
Background and objectives: The purpose of this research was to develop and validate the first prognostic nomograms for 3-, 5-, and 10-year cancer-specific survival (CSS) and overall survival (OS) in patients diagnosed with locally advanced thyroid cancer (LATC) by evaluating independent predictors of prognosis in a population of LATC patients. Methods: Demographics, clinicopathologic characteristics, treatment, and follow-up of 2396 LATC patients in the surveillance, epidemiology, and end results database from 2004 to 2015 were retrospectively analyzed and compared with patients with LATC according to staging. We randomized all LATC patients into training and validation groups in a 7:3 ratio. Cox regression analyses helped us to derive independent prognostic factors for LATC patients. According to these results, we established and validated the first prognostic nomograms and risk stratification. Results: In our research, the clinical information of LATC patients was compared and significant differences were found in the relevant variables including CSS and OS (P < 0.05), with CSS of 82.0 % and 49.0 %, and OS of 70.6 % and 40.0 %, respectively. Cox regression analyses showed that age at diagnosis, tumor diameter, presence of DM, extrathyroidal extension sites, histological type, thyroidectomy scope, radiotherapy status, and chronological sequence of radiotherapy and surgery were observably correlated with CSS in LATC patients, and in addition to the above factors, gender, marital status, and chemotherapy status were also observably correlated with OS in LATC patients. The prognostic predictive power of the above factors is visualized by the Kaplan-Meier survival curve. The concordance index of nomograms for CSS and OS were 0.933, 0.925, and 0.926 (CSS), 0.918, 0.909, and 0.906 (OS), respectively, and the time-dependent receiver operating characteristic curve, area under curve, calibration curve and decision curve analysis curve indicate that the nomograms have good discriminatory ability, accuracy and clinical applicability in both the training and validation groups. Conclusions: In these findings, we drawed a conclusion that there were significant differences in clinical information between patients with T4a and T4b LATC, and we established and validated the first prognostic nomograms and risk stratification of CSS and OS for LATC patients at 3, 5, and 10 years, which will help clinicians to individualize their postoperative treatment and individualized follow-up.
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BACKGROUND: The aim of this study was to evaluate independent predictors of prognosis in patients with mixed medullary and follicular cell carcinoma (MMFCC) and to establish the novel prognostic nomograms in the academic community for 3-, 5-, and 10 year CSS and OS in patients with MMFCC. METHODS: Demographic information, clinicopathological characteristics, treatment information, and survival status information of 200 patients with MMFCC and 6615 patients with medullary thyroid carcinoma (MTC) from 2000 to 2020 in the SEER database were retrospectively analyzed. Independent predictors of prognosis in MMFCC patients were derived using univariate and multivariate Cox regression analyses after relevant comparisons based on pathologic typing. On this basis, we developed and validated clinical prognostic nomograms and risk-stratified the patient population. RESULTS: In this study, the clinical information of 200 patients with MMFCC was compared with that of 5947 patients with MTC (NOS) and 668 patients with MTC with amyloid stroma, and there was a significant difference in the relevant variables among the three, with the CSS being 88.5%, 87.5%, and 90.9%, and the OS being 76.5%, 75.4%, and 83.8%. Univariate and multivariate Cox regression analyses yielded that age at diagnosis, presence of distant metastases, thyroidectomy scope, and lymph node dissection status were significantly correlated with the prognosis of patients (P < 0.05), and were independent predictors of CSS and OS for patients with MMFCC, and the Kaplan-Meier survival curves plotted by these factors demonstrated their predictive power for the prognosis of patients with MMFCC. The concordance index of the prognostic nomograms of CSS and OS established on this basis was 0.838 and 0.794, respectively, and the time-dependent area under curve, calibration curve, and decision curve analysis curve showed that the model had good discriminative ability, accuracy, and clinical applicability. CONCLUSIONS: In this study, we concluded that there are large differences between MMFCC and MTC in terms of demographic information, clinicopathological characteristics, treatment information, and survival status information, and we constructed the novel prognostic nomograms for 3-, 5-, and 10 year CSS and OS for patients with MMFCC with risk stratification, which will help clinicians to develop individualized protocols for their postoperative treatments and follow-ups.
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Carcinoma Neuroendocrino , Nomogramas , Humanos , Pronóstico , Estudios Retrospectivos , Carcinoma Neuroendocrino/terapia , Programa de VERF , Estadificación de NeoplasiasRESUMEN
Background: Nephronophthisis (NPH) is the most common genetic cause of end-stage renal disease (ESRD) in childhood, and NPHP1 is the major pathogenic gene. Cyst formation at the corticomedullary junction is a pathological feature of NPH, but the mechanism underlying cystogenesis is not well understood. The isolation and identification of cystic cell subpopulation could help to identify their origins and provide vital clues to the mechanisms underlying cystogenesis in NPH. Methods: Single-nucleus RNA sequencing (snRNA-seq) was performed to produce an atlas of NPHP1 renal cells. Kidney samples were collected from WT (Nphp1 +/+) mice and NPHP1 (Nphp1 del2-20/del2-20) model mice. Results: A comprehensive atlas of the renal cellular landscape in NPHP1 was generated, consisting of 14 basic renal cell types as well as a subpopulation of DCT cells that was overrepresented in NPHP1 kidneys compared to WT kidneys. GO analysis revealed significant downregulation of genes associated with tubular development and kidney morphogenesis in this subpopulation. Furthermore, the reconstruction of differentiation trajectories of individual cells within this subpopulation confirmed that a specific group of cells in NPHP1 mice become arrested at an early stage of differentiation and proliferate to form cysts. We demonstrate that Niban1 is a specific molecular marker of cystic cells in both mice and human NPHP1. Conclusion: In summary, we report a novel subpopulation of DCT cells, marked by Niban1, that are classified as cystic cells in the NPHP1 mice kidney. These results offer fresh insights into the cellular and molecular basis of cystogenesis in NPH.
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BACKGROUND: This study was conducted to develop nomograms and validate them by assessing risk factors for the development of central lymph node metastasis (CLNM) in patients with solitary papillary thyroid carcinoma of the isthmus (PTCI) for predicting the probability of CLNM. METHODS: Demographic and clinicopathological variables of patients with solitary papillary thyroid carcinoma (PTC) from May 2018 to May 2023 at the First Hospital of Shanxi Medical University were retrospectively analyzed, and the lobar group and the isthmus group were divided according to tumor location. Patients with the same sex, age difference of less than 3 years, and equal gross tumor diameter were selected from the lobar group and compared with the paraisthmic tumor group. Independent risk factors were determined using univariate and multivariate logistic regression analysis. On this basis, clinical predictive nomograms were developed and validated. RESULTS: Clinical data from 326 patients with solitary PTCI and 660 cases of solitary lobar PTC were used for analysis in our study. The incidence of solitary tumors CLNM located in the median isthmus, paracentral isthmus, and lobes was 69.8%, 40.9%, and 33.6%, respectively. Statistical analysis revealed that gender, age, isthmus location, maximum nodal diameter, the presence of possible CLNM in advance on preoperative ultrasound, chronic lymphocytic thyroiditis, and the lymphocyte/monocyte ratio were independent risk factors for preoperative CLNM in patients with solitary PTCI. Age, isthmus location, chronic lymphocytic thyroiditis, gross tumor diameter, presence of intraoperative extrathyroidal extension, and presence of metastasis in the Delphian lymph node on frozen section were independent risk factors for intraoperative CLNM. The concordance indices of nomograms for preoperative and intraoperative are 0.871 and 0.894 in the training set and 0.796 and 0.851 in the validation set, calibration curve and decision curve analysis also demonstrated the strong reliability and clinical applicability of this clinical prediction model. CONCLUSION: In this study, we concluded that solitary PTCI is more aggressive compared to solitary lobar PTC, and we constructed nomograms and risk stratification to accurately identify patients with solitary PTCI who are at high risk of developing CLNM, which will help clinicians in personalized decision making.
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Enfermedad de Hashimoto , Neoplasias de la Tiroides , Humanos , Preescolar , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Nomogramas , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Enfermedad de Hashimoto/patología , Estudios Retrospectivos , Metástasis Linfática/patología , Modelos Estadísticos , Reproducibilidad de los Resultados , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Pronóstico , Factores de RiesgoRESUMEN
In this study, a nomogram was established and validated by assessing the risk factors for the development of pulmonary metastases in patients with non-papillary thyroid carcinoma (NPTC) and was used to predict the risk of developing pulmonary metastases. Demographic and clinicopathological variables of patients with NPTC from 2010 to 2015 in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed, and independent risk factors were identified using χ2 tests and full subset regression analysis. Based on this, a nomogram was developed and validated for predicting the risk of pulmonary metastasis in patients with NPTC. The predictive performance of the nomogram was calculated using the consistency index, and the clinical application value of the nomogram was evaluated using calibration curve and decision curve analyses. In addition, risk stratification of patients with NPTC based on these results was performed to facilitate early diagnosis and treatment of patients with pulmonary metastases in the clinic. Data from 1435 patients with NPTC were used for the analysis based on the inclusion and exclusion criteria. Statistical analysis yielded a high risk of pulmonary metastasis in patients with older age, high T-stage, poorly differentiated, undifferentiated thyroid carcinoma, follicular thyroid carcinoma (NOS), and the presence of other distant metastases. We further developed a nomogram with a consistency index of 0.898 (95% confidence interval: 0.880-0.920) in the training cohort and 0.895 (95% confidence interval: 0.862-0.927) in the validation cohort. The calibration curve and decision curve analyses also demonstrated the strong reliability and accuracy of this clinical prediction model. In this study, a nomogram was constructed to accurately identify patients with NPTC at a high risk of pulmonary metastasis, which will help clinicians in personalized decision-making.
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Neoplasias Pulmonares , Neoplasias de la Tiroides , Humanos , Nomogramas , Modelos Estadísticos , Pronóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/epidemiologíaRESUMEN
The RNA binding protein (RBP) and non-coding RNA (ncRNA) interacting networks are increasingly recognized as the main mechanism in gene regulation, and are tightly associated with cellular malfunction and disease. Here, we present fRNC, a systems biology tool to uncover the dynamic spectrum of RBP-ncRNA circuits (RNC) by integrating transcriptomics, interactomics and proteomics data. fRNC constructs the RBP-ncRNA network derived from CLIP-seq or PARE experiments. Given scoring on nodes and edges according to differential analysis of expression data, it finds an RNC containing global maximum significant RBPs and ncRNAs. Alternatively, it can also capture the locally maximum scoring RNC according to user-defined starting nodes with the greedy search. When compared with existing tools, fRNC can detect more accurate and robust sub-network with scalability. As shown in the cases of esophageal carcinoma, breast cancer and Alzheimer's disease, fRNC enables users to analyze the collective behaviors between RBP and the interacting ncRNAs, and reveal novel insights into the disease-associated processes. The fRNC R package is available at https://github.com/BioinformaticsSTU/fRNC.
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The self-paced reading paradigm has been popular and widely used in psycholinguistic research for several decades. The tool described in this paper, FAB (Forward and Backward reading), is a tool created to hopefully and maximally reduce the coding demands and simplify the operation costs for experimental researchers and clinical researchers who are doing experimental work, in their designing, coding, implementing, and analyzing self-paced reading tasks. Its basis in web languages (HTML, JavaScript) also promotes experimental implementation and material sharing in our era of open science. In addition, FAB has a unique forward-and-backward mode that can track regressive-like behaviors that are usually only recordable using eye-tracking or mouse-tracking equipment. In this paper, the specific application and usage of FAB is demonstrated in one laboratory and two online validation experiments. We hope this free and open-sourced tool can benefit research in a diverse range of contexts where self-paced reading is desirable.
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Lenguaje , Lectura , Humanos , PsicolingüísticaRESUMEN
Accumulation of obsolete biomolecules can accelerate cell senescence and organism aging. The two efficient intracellular systems, namely the ubiquitin-proteasome system and the autophagy-lysosome system, play important roles in dealing with cellular wastes. However, how multicellular organisms orchestrate the processing of obsolete molecules and delay aging remains unclear. Herein, it is shown that prevention of exosome release by GW4869 or Rab27a-/- accelerated senescence in various cells and mice, while stimulating exosome release by nutrient restriction delays aging. Interestingly, exosomes isolate from serum-deprived cells or diet-restricted human plasma, enriched with garbage biomolecules, including misfolded proteins, oxidized lipids, and proteins. These cellular wastes can be englobed by macrophages, eventually, for disintegration in vivo. Inhibition of nutrient-sensing mTORC1 signaling increases exosome release and delays senescence, while constitutive activation of mTORC1 reduces exosome secretion and exacerbates senescence in vitro and in mice. Notably, inhibition of exosome release attenuates nutrient restriction- or rapamycin-delayed senescence, supporting a key role for exosome secretion in this process. This study reveals a potential mechanism by which stimulated exosome release delays aging in multicellular organisms, by orchestrating the harmful biomolecules disposal via exosomes and macrophages.
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Exosomas , Humanos , Animales , Ratones , Exosomas/metabolismo , Línea Celular , Células Cultivadas , Células Epiteliales , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismoRESUMEN
Electrocatalytic hydrogen evolution reaction (HER) in alkaline media is important for hydrogen economy but suffers from sluggish reaction kinetics due to a large water dissociation energy barrier. Herein, Pt5 P2 nanocrystals anchoring on amorphous nickel phosphate nanorods as a high-performance interfacial electrocatalyst system (Pt5 P2 NCs/a-NiPi) for the alkaline HER are demonstrated. At the unique polycrystalline/amorphous interface with abundant defects, strong electronic interaction, and optimized intermediate adsorption strength, water dissociation is accelerated over abundant oxophilic Ni sites of amorphous NiPi, while hydride coupling is promoted on the adjacent electron-rich Pt sites of Pt5 P2 . Meanwhile, the ultra-small-sized Pt5 P2 nanocrystals and amorphous NiPi nanorods maximize the density of interfacial active sites for the Volmer-Tafel reaction. Pt5 P2 NCs/a-NiPi exhibits small overpotentials of merely 9 and 41 mV at -10 and -100 mA cm-2 in 1 M KOH, respectively. Notably, Pt5 P2 NCs/a-NiPi exhibits an unprecedentedly high mass activity (MA) of 14.9 mA µgPt -1 at an overpotential of 70 mV, which is 80 times higher than that of Pt/C and represents the highest MA of reported Pt-based electrocatalysts for the alkaline HER. This work demonstrates a phosphorization and interfacing strategy for promoting Pt utilization and in-depth mechanistic insights for the alkaline HER.
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Circular RNAs (circRNAs) are endogenous non-coding RNAs that regulate gene expression and participate in carcinogenesis. However, the RNA-binding proteins (RBPs) involved in circRNAs biogenesis and modulation remain largely unclear. We developed the circRNA regulator identification tool (CRIT), a non-negative matrix-factorization-based pipeline to identify regulating RBPs in cancers. CRIT uncovered 73 novel regulators across thousands of samples by effectively leveraging genomics data and functional annotations. We demonstrated that known RBPs involved in circRNA control are significantly enriched in these predictions. Analysis of circRNA-RBP interactions using two large cross-linking immunoprecipitation (CLIP) databases, we validated the consistency between CRIT prediction and the CLIP experiments. Furthermore, newly discovered RBPs are functionally connected with authentic circRNA regulators by various biological associations, such as physical interaction, similar binding motifs, common transcription factor modulation, and co-expression. When analyzing RNA sequencing (RNA-seq) datasets after short hairpin RNA (shRNA)/small interfering RNA (siRNA) knockdown, we found several novel RBPs that can affect global circRNA expression, which strengthens their role in the circRNA life cycle. The above evidence provided independent confirmation that CRIT is a useful tool to capture RBPs in circRNA processing. Finally, we show that authentic regulators are more likely the core splicing proteins and peripheral factors and usually harbor more alterations in the vast majority of cancers.
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An ultrasensitive plasmonic near-infrared fluorescent biosensor substrate has been developed for detection of glial fibrillary acidic protein (GFAP) biomarker in blood plasma, an important protein biomarker of traumatic brain injury (TBI). To minimize the interference from blood plasma sample matrix, a near-infrared fluorophore in the first biological transparency window is used in the biosensor. To amplify the fluorescence signals, a plasmonic gold nanopyramid array has been coupled to the fluorophore. Finite-difference time-domain simulation reveals that the excitation enhancement is primarily responsible for the fluorescence enhancement owing to the intense local electric field excited on the corners and edges. As a result, this biosensor exhibits a lower limit of detection of 0.6 pg/mL toward detection of GFAP in blood plasma.
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Lesiones Traumáticas del Encéfalo , Proteína Ácida Fibrilar de la Glía , Biomarcadores/sangre , Técnicas Biosensibles , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Fluorescencia , Proteína Ácida Fibrilar de la Glía/sangre , HumanosRESUMEN
BACKGROUND: Infectious diseases of farmed and wild animals pose a recurrent threat to food security and human health. The macrophage, a key component of the innate immune system, is the first line of defence against many infectious agents and plays a major role in shaping the adaptive immune response. However, this phagocyte is a target and host for many pathogens. Understanding the molecular basis of interactions between macrophages and pathogens is therefore crucial for the development of effective strategies to combat important infectious diseases. RESULTS: We explored how porcine pluripotent stem cells (PSCs) can provide a limitless in vitro supply of genetically and experimentally tractable macrophages. Porcine PSC-derived macrophages (PSCdMs) exhibited molecular and functional characteristics of ex vivo primary macrophages and were productively infected by pig pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV) and African swine fever virus (ASFV), two of the most economically important and devastating viruses in pig farming. Moreover, porcine PSCdMs were readily amenable to genetic modification by CRISPR/Cas9 gene editing applied either in parental stem cells or directly in the macrophages by lentiviral vector transduction. CONCLUSIONS: We show that porcine PSCdMs exhibit key macrophage characteristics, including infection by a range of commercially relevant pig pathogens. In addition, genetic engineering of PSCs and PSCdMs affords new opportunities for functional analysis of macrophage biology in an important livestock species. PSCs and differentiated derivatives should therefore represent a useful and ethical experimental platform to investigate the genetic and molecular basis of host-pathogen interactions in pigs, and also have wider applications in livestock.
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Virus de la Fiebre Porcina Africana , Enfermedades Transmisibles , Virus de la Fiebre Porcina Africana/genética , Animales , Interacciones Huésped-Patógeno/genética , Macrófagos , Células Madre , PorcinosRESUMEN
BACKGROUND & AIMS: Hepatosteatosis, defined as excessive intrahepatic lipid accumulation, represents the first step of NAFLD. When combined with additional cellular stress, this benign status progresses to local and systemic pathological conditions such as NASH and insulin resistance. However, the molecular events directly caused by hepatic lipid build-up, in terms of its impact on liver biology and peripheral organs, remain unclear. Carnitine palmitoyltransferase 1A (CPT1A) is the rate limiting enzyme for long chain fatty acid beta-oxidation in the liver. Here we utilise hepatocyte-specific Cpt1a knockout (LKO) mice to investigate the physiological consequences of abolishing hepatic long chain fatty acid metabolism. APPROACH & RESULTS: Compared to the wild-type (WT) littermates, high fat diet (HFD)-fed LKO mice displayed more severe hepatosteatosis but were otherwise protected against diet-induced weight gain, insulin resistance, hepatic ER stress, inflammation and damage. Interestingly, increased energy expenditure was observed in LKO mice, accompanied by enhanced adipose tissue browning. RNAseq analysis revealed that the peroxisome proliferator activator alpha (PPARα)- fibroblast growth factor 21 (FGF21) axis was activated in liver of LKO mice. Importantly, antibody-mediated neutralization of FGF21 abolished the healthier metabolic phenotype and adipose browning in LKO mice, indicating that the elevation of FGF21 contributes to the improved liver pathology and adipose browning in HFD-treated LKO mice. CONCLUSIONS: Liver with deficient CPT1A expression adopts a healthy steatotic status that protects against HFD-evoked liver damage and potentiates adipose browning in an FGF21-dependent manner. Inhibition of hepatic CPT1A may serve as a viable strategy for the treatment of obesity and NAFLD.
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Cotton is the most important fiber crop and provides indispensable natural fibers for the textile industry. Micronaire (MIC) is determined by fiber fineness and maturity and is an important component of fiber quality. Gossypium barbadense L. possesses long, strong and fine fibers, while upland cotton (Gossypium hirsutum L.) is high yielding with high MIC and widely cultivated worldwide. To identify quantitative trait loci (QTLs) and candidate genes for MIC in G. barbadense, a population of 250 backcross inbred lines (BILs), developed from an interspecific cross of upland cotton CRI36 × Egyptian cotton (G. barbadense) Hai7124, was evaluated in 9 replicated field tests. Based on a high-density genetic map with 7709 genotyping-by-sequencing (GBS)-based single-nucleotide polymorphism (SNP) markers, 25 MIC QTLs were identified, including 12 previously described QTLs and 13 new QTLs. Importantly, two stable MIC QTLs (qMIC-D03-2 on D03 and qMIC-D08-1 on D08) were identified. Of a total of 338 genes identified within the two QTL regions, eight candidate genes with differential expression between TM-1 and Hai7124 were identified. Our research provides valuable information for improving MIC in cotton breeding.