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Long noncoding RNAs (lncRNAs) evolve more rapidly than mRNAs. Whether conserved lncRNAs undergo conserved processing, localization, and function remains unexplored. We report differing subcellular localization of lncRNAs in human and mouse embryonic stem cells (ESCs). A significantly higher fraction of lncRNAs is localized in the cytoplasm of hESCs than in mESCs. This turns out to be important for hESC pluripotency. FAST is a positionally conserved lncRNA but is not conserved in its processing and localization. In hESCs, cytoplasm-localized hFAST binds to the WD40 domain of the E3 ubiquitin ligase ß-TrCP and blocks its interaction with phosphorylated ß-catenin to prevent degradation, leading to activated WNT signaling, required for pluripotency. In contrast, mFast is nuclear retained in mESCs, and its processing is suppressed by the splicing factor PPIE, which is highly expressed in mESCs but not hESCs. These findings reveal that lncRNA processing and localization are previously under-appreciated contributors to the rapid evolution of function.
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Espaço Intracelular/genética , RNA Longo não Codificante/metabolismo , Células-Tronco/metabolismo , Animais , Diferenciação Celular/genética , Linhagem Celular , Células Cultivadas , Células-Tronco Embrionárias/metabolismo , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo , Splicing de RNA/genética , RNA Longo não Codificante/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Células-Tronco/patologiaRESUMO
The metazoan-specific Integrator complex catalyzes 3' end processing of small nuclear RNAs (snRNAs) and premature termination that attenuates the transcription of many protein-coding genes. Integrator has RNA endonuclease and protein phosphatase activities, but it remains unclear if both are required for complex function. Here, we show IntS6 (Integrator subunit 6) over-expression blocks Integrator function at a subset of Drosophila protein-coding genes, although having no effect on snRNAs or attenuation of other loci. Over-expressed IntS6 titrates protein phosphatase 2A (PP2A) subunits, thereby only affecting gene loci where phosphatase activity is necessary for Integrator function. IntS6 functions analogous to a PP2A regulatory B subunit as over-expression of canonical B subunits, which do not bind Integrator, is also sufficient to inhibit Integrator activity. These results show that the phosphatase module is critical at only a subset of Integrator-regulated genes and point to PP2A recruitment as a tunable step that modulates transcription termination efficiency.
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Proteínas de Drosophila , Terminação da Transcrição Genética , Animais , RNA , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , RNA Nuclear Pequeno/genética , Fatores de Transcrição/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogasterRESUMO
Numerous circular RNAs (circRNAs) produced from back-splicing of exon(s) have been recently revealed on a genome-wide scale across species. Although generally expressed at a low level, some relatively abundant circRNAs can play regulatory roles in various biological processes, prompting continuous profiling of circRNA in broader conditions. Over the past decade, distinct strategies have been applied in both transcriptome enrichment and bioinformatic tools for detecting and quantifying circRNAs. Understanding the scope and limitations of these strategies is crucial for the subsequent annotation and characterization of circRNAs, especially those with functional potential. Here, we provide an overview of different transcriptome enrichment, deep sequencing and computational approaches for genome-wide circRNA identification, and discuss strategies for accurate quantification and characterization of circRNA.
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RNA Circular , RNA , RNA Circular/genética , RNA/genética , Transcriptoma , Biologia Computacional , Genoma/genéticaRESUMO
There generally exists a critical state or tipping point from a stable state to another in the development of colorectal cancer (CRC) beyond which a significant qualitative transition occurs. Gut microbiome sequencing data can be collected non-invasively from fecal samples, making it more convenient to obtain. Furthermore, intestinal microbiome sequencing data contain phylogenetic information at various levels, which can be used to reliably identify critical states, thereby providing early warning signals more accurately and effectively. Yet, pinpointing the critical states using gut microbiome data presents a formidable challenge due to the high dimension and strong noise of gut microbiome data. To address this challenge, we introduce a novel approach termed the specific network information gain (SNIG) method to detect CRC's critical states at various taxonomic levels via gut microbiome data. The numerical simulation indicates that the SNIG method is robust under different noise levels and that it is also superior to the existing methods on detecting the critical states. Moreover, utilizing SNIG on two real CRC datasets enabled us to discern the critical states preceding deterioration and to successfully identify their associated dynamic network biomarkers at different taxonomic levels. Notably, we discovered certain 'dark species' and pathways intimately linked to CRC progression. In addition, we accurately detected the tipping points on an individual dataset of type I diabetes.
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Neoplasias Colorretais , Diabetes Mellitus Tipo 1 , Microbioma Gastrointestinal , Humanos , Filogenia , Simulação por Computador , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genéticaRESUMO
Base editing of hematopoietic stem/progenitor cells (HSPCs) is an attractive strategy for treating immunohematologic diseases. However, the feasibility of using adenine-base-edited HSPCs for treating X-linked severe combined immunodeficiency (SCID-X1), the influence of dose-response relationships on immune cell generation, and the potential risks have not been demonstrated in vivo. Here, a humanized SCID-X1 mouse model was established, and 86.67% ± 2.52% (n = 3) of mouse hematopoietic stem cell (HSC) pathogenic mutations were corrected, with no single-guide-RNA (sgRNA)-dependent off-target effects detected. Analysis of peripheral blood over 16 weeks post-transplantation in mice with different immunodeficiency backgrounds revealed efficient immune cell generation following transplantation of different amounts of modified HSCs. Therefore, a large-scale infusion of gene-corrected HSCs within a safe range can achieve rapid, stable, and durable immune cell regeneration. Tissue-section staining further demonstrated the restoration of immune organ tissue structures, with no tumor formation in multiple organs. Collectively, these data suggest that base-edited HSCs are a potential therapeutic approach for SCID-X1 and that a threshold infusion dose of gene-corrected cells is required for immune cell regeneration. This study lays a theoretical foundation for the clinical application of base-edited HSCs in treating SCID-X1.
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Adenina , Linfócitos B , Modelos Animais de Doenças , Edição de Genes , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Linfócitos T , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X , Animais , Camundongos , Células-Tronco Hematopoéticas/metabolismo , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/terapia , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/genética , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Humanos , Adenina/análogos & derivados , Linfócitos B/imunologia , Linfócitos B/metabolismo , Camundongos SCID , Terapia Genética/métodos , Sistemas CRISPR-Cas , RNA Guia de Sistemas CRISPR-CasRESUMO
Interface phonon modes that are generated by several atomic layers at the heterointerface play a major role in the interface thermal conductance for nanoscale high-power devices such as nitride-based high-electron-mobility transistors and light-emitting diodes. Here we measure the local phonon spectra across AlN/Si and AlN/Al interfaces using atomically resolved vibrational electron energy-loss spectroscopy in a scanning transmission electron microscope. At the AlN/Si interface, we observe various interface phonon modes, of which the extended and localized modes act as bridges to connect the bulk AlN modes and bulk Si modes and are expected to boost the phonon transport, thus substantially contributing to interface thermal conductance. In comparison, no such phonon bridge is observed at the AlN/Al interface, for which partially extended modes dominate the interface thermal conductivity. This work provides valuable insights into understanding the interfacial thermal transport in nitride semiconductors and useful guidance for thermal management via interface engineering.
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Spontaneous abortion is the most common complication in early pregnancy, the exact etiology of most cases cannot be determined. Emerging studies suggest that mutations in ciliary genes may be associated with progression of pregnancy loss. However, the involvement of primary cilia on spontaneous abortion and the underlying molecular mechanisms remains poorly understood. We observed the number and length of primary cilia were significantly decreased in decidua of spontaneous abortion in human and lipopolysaccharide (LPS)-induced abortion mice model, accompanied with increased expression of proinflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. The length of primary cilia in human endometrial stromal cell (hESC) was significantly shortened after TNF-α treatment. Knocking down intraflagellar transport 88 (IFT88), involved in cilia formation and maintenance, promoted the expression of TNF-α. There was a reverse regulatory relationship between cilia shortening and TNF-α expression. Further research found that shortened cilia impair decidualization in hESC through transforming growth factor (TGF)-ß/SMAD2/3 signaling. Primary cilia were impaired in decidua tissue of spontaneous abortion, which might be mainly caused by inflammatory injury. Primary cilia abnormalities resulted in dysregulation of TGF-ß/SMAD2/3 signaling transduction and decidualization impairment, which led to spontaneous abortion.
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Aborto Espontâneo , Cílios , Transdução de Sinais , Proteína Smad2 , Proteína Smad3 , Fator de Crescimento Transformador beta , Feminino , Cílios/metabolismo , Cílios/patologia , Aborto Espontâneo/metabolismo , Aborto Espontâneo/patologia , Humanos , Proteína Smad2/metabolismo , Proteína Smad2/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/genética , Animais , Proteína Smad3/metabolismo , Proteína Smad3/genética , Gravidez , Camundongos , Decídua/metabolismo , Decídua/patologia , Fator de Necrose Tumoral alfa/metabolismo , Células Estromais/metabolismo , Células Estromais/patologiaRESUMO
Joubert syndrome (JBTS) is a systematic developmental disorder mainly characterized by a pathognomonic mid-hindbrain malformation. All known JBTS-associated genes encode proteins involved in the function of antenna-like cellular organelle, primary cilium, which plays essential roles in cellular signal transduction and development. Here, we identified four unreported variants in ARL13B in two patients with the classical features of JBTS. ARL13B is a member of the Ras GTPase family and functions in ciliogenesis and cilia-related signaling. The two missense variants in ARL13B harbored the substitutions of amino acids at evolutionarily conserved positions. Using model cell lines, we found that the accumulations of the missense variants in cilia were impaired and the variants showed attenuated functions in ciliogenesis or the trafficking of INPP5E. Overall, these findings expanded the ARL13B pathogenetic variant spectrum of JBTS.
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Fatores de Ribosilação do ADP , Anormalidades Múltiplas , Cerebelo , Anormalidades do Olho , Doenças Renais Císticas , Retina , Humanos , Anormalidades Múltiplas/genética , Fatores de Ribosilação do ADP/genética , Fatores de Ribosilação do ADP/metabolismo , Cerebelo/anormalidades , Cílios/genética , Anormalidades do Olho/genética , Anormalidades do Olho/metabolismo , Anormalidades do Olho/patologia , Doenças Renais Císticas/genética , Doenças Renais Císticas/metabolismo , Doenças Renais Císticas/patologia , Monoéster Fosfórico Hidrolases/metabolismo , Retina/metabolismo , Retina/anormalidades , Masculino , Feminino , LactenteRESUMO
Natural killer (NK) cells are important immune cells in the organism and are the third major type of lymphocytes besides T cells and B cells, which play an important function in cancer therapy. In addition to retaining the tumor cell killing function of natural killer cells, natural killer cell-derived exosomes cells also have the characteristics of high safety, wide source, easy to preserve and transport. At the same time, natural killer cell-derived exosomes are easy to modify, and the engineered exosomes can be used in combination with a variety of current cancer therapies, which not only enhances the therapeutic efficacy, but also significantly reduces the side effects. Therefore, this review summarizes the source, isolation and modification strategies of natural killer cell-derived exosomes and the combined application of natural killer cell-derived engineered exosomes with other antitumor therapies, which is expected to accelerate the clinical translation process of natural killer cell-derived engineered exosomes in cancer therapy.
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Exossomos , Células Matadoras Naturais , Neoplasias , Humanos , Relevância Clínica , Exossomos/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
Long-term repopulating haematopoietic stem cells (LT-HSCs) have the ability to reconstitute the entire haematopoietic system following transplantation permanently. Despite great achievements in HSC transplantation, the limited transplantable HSC number, especially LT-HSCs, remains critical for successful transplantation and broader applications. In this study, we established a defined serum-free culture system for in vitro expansion of LT-HSCs. This culture system (E1) expanded LT-HSCs from umbilical cord blood, human mobilization peripheral blood and bone marrow. These E1-expanded HSCs reconstituted the haematopoietic and immune systems in primary and secondary transplanted mice in a short time. Better haematopoietic reconstitution was observed in secondary xenografted mice. Moreover, we obtained the comprehensive expression profile and cellular components of LT-HSCs from umbilical cord blood. Our study provides a valuable tool for LT-HSC research and may improve clinical applications of HSCs.
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Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Humanos , Animais , Camundongos , Células-Tronco Hematopoéticas/metabolismo , Sangue FetalRESUMO
Conductive flexible hydrogels have attracted immense attentions recently due to their wide applications in wearable sensors. However, the poor mechanical properties of most conductive polymer limit their utilizations. Herein, a double network hydrogel is fabricated via a self-sorting process with cationic polyacrylamide as the first flexible network and the lantern[33]arene-based hydrogen organic framework nanofibers as the second rigid network. This hydrogel is endowed with good conductivity (0.25 S m-1) and mechanical properties, such as large Young's modulus (31.9 MPa), fracture elongation (487%) and toughness (6.97 MJ m-3). The stretchability of this hydrogel is greatly improved after the kirigami cutting, which makes it can be used as flexible strain sensor for monitoring human motions, such as bending of fingers, wrist and elbows. This study not only provides a valuable strategy for the construction of double network hydrogels by lanternarene, but also expands the application of the macrocycle hydrogels to flexible electronics.
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STUDY QUESTION: Do couple's age ranges for optimal fecundability, and the associations with fecundability of couple's age combinations and age differences differ with gravidity? SUMMARY ANSWER: The couple's age range of optimal fecundability and age combinations differed with gravidity, and gravidity might modify the associations of age and spousal age difference with couple's fecundability. WHAT IS KNOWN ALREADY: Age is one of the strongest determinants of fecundability, but the existing studies have certain limitations in study population, couple's extreme age combinations and age differences, and have not explored whether the association between age and fecundability differs with gravidity. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study. 5â407â499 general reproductive-aged couples (not diagnosed with infertility) participated in the National Free Pre-conception Check-up Projects during 2015-2017. They were followed up for pregnancy outcomes through telephone interviews every 3 months until they became pregnant or were followed up for 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS: The main outcome was time to pregnancy, and the fecundability odds ratios and 95% CIs were estimated using the Cox models for discrete survival time. The associations of age and spousal age difference with fecundability were evaluated by restricted cubic splines. MAIN RESULTS AND THE ROLE OF CHANCE: In this large cohort of general reproductive-aged population, the age of optimal fecundability of multigravida couples was older than that of nulligravida couples, but their subsequent fecundability declined more sharply with age. The decline in female fecundability was more pronounced with age, with fecundability dropping by â¼30% in both nulligravida and multigravida couples whose female partners aged ≥35 years. In the nulligravida group, the fecundability of couples who were both ≤24 years with the same age was the highest, which decreased steadily with the increase of spousal age difference, and younger male partners did not seem to contribute to improving couple's fecundability. In the multigravida group, couples with female partners aged 25-34 years and a spousal age difference of -5 to 5 years showed higher fecundability, and the effect of spousal age difference on couple's fecundability became suddenly apparent when female partners aged around 40 years. Young male partners were unable to change the decisive effect of female partner's age over 40 years on couple's reduced fecundability, regardless of gravidity. LIMITATIONS, REASONS FOR CAUTION: Lacking the time for couples to attempt pregnancy before enrollment, and some couples might suspend pregnancy plans during follow-up because of certain emergencies, which would misestimate the fecundability. Due to the lack of information on sperm quality and sexual frequency of couples, we could not adjust for these factors. Moreover, due to population characteristics, the extrapolation of our results required caution. WIDER IMPLICATIONS OF THE FINDINGS: The couple's age range of optimal fecundability, age combinations, and spousal age difference on fecundability varied with gravidity. Female age-related decline in fecundability was more dominant in couple's fecundability. Targeted fertility guidance should be provided to couples with different age combinations and gravidities. STUDY FUNDING/COMPETING INTEREST(S): This research received funding from the Project of National Research Institute for Family Planning (Grant No. 2018NRIFPJ03), the National Key Research and Development Program of China (Grant No. 2016YFC1000307), and the National Human Genetic Resources Sharing Service Platform (Grant No. 2005DKA21300), People's Republic of China. The funders had no role in study design, analysis, decision to publish, or preparation of the manuscript. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
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Número de Gestações , Sêmen , Gravidez , Masculino , Humanos , Feminino , Adulto , Estudos de Coortes , Estudos Retrospectivos , Fertilidade , Tempo para EngravidarRESUMO
STUDY QUESTION: Do prepregnancy peripheral leukocytes (PPLs) and their subsets influence the risk of spontaneous abortion (SAB)? SUMMARY ANSWER: PPLs and their subsets are associated with the risk of SAB. WHAT IS KNOWN ALREADY: Compelling studies have revealed the crucial role of maternal peripheral leukocytes in embryo implantation and pregnancy maintenance. Adaptive changes are made by PPLs and their subsets after conception. STUDY DESIGN, SIZE, DURATION: This population-based retrospective cohort study was based on data from the National Free Pre-pregnancy Check-up Project (NFPCP) in mainland China. Couples preparing for pregnancy within the next six months were provided with free prepregnancy health examinations and counseling services for reproductive health. The current study was based on 1 310 494 female NFPCP participants aged 20-49 who became pregnant in 2016. After sequentially excluding 235 456 participants lost to follow-up, with multiple births, and who failed to complete blood tests, a total of 1 075 038 participants were included in the primary analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: PPLs and their subset counts and ratios were measured. The main outcome was SAB. A multivariable logistic regression model was used to estimate the odds ratio (OR) and 95% CI of SAB associated with PPLs and their subsets, and restricted cubic spline (RCS) was used to estimate the nonlinear exposure-response relationship. MAIN RESULTS AND ROLE OF CHANCE: Of the included pregnant participants, a total of 35 529 SAB events (3.30%) were recorded. Compared to participants with reference values of PPLs, the ORs (95% CIs) of leukopenia and leukocytosis for SAB were 1.14 (1.09-1.20) and 0.74 (0.69-0.79), respectively. The RCS result revealed a monotonous decreasing trend (Pnonlinear < 0.05). Similar relationships were observed for the neutrophil count and ratio, monocyte count, and middle-sized cell count and ratio. The lymphocyte ratio showed a positive and nonlinear relationship with the risk of SAB (Pnonlinear < 0.05). Both eosinophils and basophils showed positive relationships with the risk of SAB (eosinophil Pnonlinear > 0.05 and basophil Pnonlinear < 0.05). LIMITATIONS, REASONS FOR CAUTION: Chemical abortion events and the cause of SAB were not collected at follow-up. Whether women with abnormal PPLs had recovered during periconception was not determined. WIDER IMPLICATIONS OF THE FINDINGS: PPLs and their subsets are associated with the risk of SAB. Leukopenia and neutropenia screening in women preparing for pregnancy and developing a feasible PPL stimulation approach should be emphasized to utilize the immune window of opportunity to prevent SAB. STUDY FUNDING/COMPETING INTEREST(S): This study was approved by the Institutional Research Review Board of the National Health and Family Planning Commission. This study was supported by the National Key Research and Development Program of China (grants 2021YFC2700705 [Y.Y.] and 2016YFC100307 [X.M.]) and the National Natural Science Foundation of China (grant no. 82003472 [L.W.]). The funding source was not involved in the study design, data collection, analysis and interpretation of the data, writing the report, or the decision to submit this article for publication. No competing interests. TRIAL REGISTRATION NUMBER: N/A.
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Aborto Induzido , Aborto Espontâneo , Leucopenia , Gravidez , Animais , Feminino , Humanos , Cavalos , Aborto Espontâneo/etiologia , Estudos Retrospectivos , Aborto Induzido/efeitos adversos , Leucócitos , Leucopenia/complicaçõesRESUMO
Diabetic retinopathy (DR) is a main factor affecting vision of patients, and its pathogenesis is not completely clear. The purpose of our study was to investigate correlations between MST2 and DR progression, and to study the possible mechanism of MST2 and its down pathway in high glucose (HG)-mediated RGC-5 apoptosis. The diabetic rat model was established by intraperitoneal injection of streptozotocin (STZ) 60 mg/kg. HE and TUNEL staining were used to evaluate the pathological changes and apoptosis of retinal cells in rats. Western blot, qRT-PCR and immunohistochemistry showed that levels of MST2 were increased in diabetic group (DM) than control. In addition, the differential expression of MST2 is related to HG-induced apoptosis of RGC-5 cells. CCK-8 and Hoechst 33,342 apoptosis experiments showed that MST2 was required in HG-induced apoptosis of RGC-5 cells. Further research revealed that MST2 regulated the protein expression of YAP1 at the level of phosphorylation in HG-induced apoptosis. Simultaneously, we found that Xmu-mp-1 acts as a MST2 inhibitor to alleviate HG-induced apoptosis. In summary, our study indicates that the MST2/YAP1 signaling pathway plays an important role in DR pathogenesis and RGC-5 apoptosis. This discovery provides new opportunities for future drug development targeting this pathway to prevent DR.
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Diabetes Mellitus Experimental , Retinopatia Diabética , Humanos , Ratos , Animais , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Diabetes Mellitus Experimental/complicações , Transdução de Sinais , Apoptose , Marcação In Situ das Extremidades CortadasRESUMO
BACKGROUND: Phenylketonuria (PKU) is a common, congenital, autosomal recessive, metabolic disorder caused by Phenylalanine hydroxylase (PAH) variants. METHODS: 967 PKU patients from Gansu, China were genotyped by Sanger sequencing, multiplex ligation-dependent probe amplification, and whole exome sequencing. We analyzed the variants of PAH exons, their flanking sequences, and introns. RESULTS: The detection of deep intronic variants in PAH gene can significantly improve the genetic diagnostic rate of PKU. The distribution of PAH variants among PKU subtypes may be related to the unique genetic background in Gansu, China. CONCLUSION: The identification of PAH hotspot variants will aid the development of large-scale neonatal genetic screening for PKU. The five new PAH variants found in this study further expand the spectrum of PAH variants. Genotype-phenotype correlation analysis may help predict the prognosis of PKU patients and enable precise treatment regimens to be developed.
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Fenilalanina Hidroxilase , Fenilcetonúrias , Humanos , Fenilalanina Hidroxilase/genética , Fenilalanina Hidroxilase/metabolismo , Fenilcetonúrias/genética , Fenilcetonúrias/diagnóstico , Mutação , Genótipo , Estudos de Associação Genética , China , FenótipoRESUMO
We aimed to explore the association between the serum 25-hydroxyvitamin D concentration and all-cause and cancer-specific mortality in 2,463 adult patients with cancer from the National Health and Nutrition Examination Survey 2007-2018. We linked mortality data from the survey to the National Death Index records up to December 31, 2019. During a median follow-up period of 70 months, 567 patients died, of whom 194 died due to cancer. Multivariate adjustment was performed for demographic characteristics, lifestyle, dietary factors, 25-hydroxyvitamin D testing period, and cancer site. Higher serum 25-hydroxyvitamin D concentrations up to 75 nmol/L significantly reduced the risk of all-cause and cancer-specific mortality. When 25-hydroxyvitamin D quartiles were compared, the multivariable-adjusted hazard ratios were 0.59 (95% confidence interval: 0.42, 0.84) for all-cause mortality (P for trend <0.001) and 0.48 (95% confidence interval: 0.29, 0.79) for cancer-specific mortality (P for trend = 0.037) in quartile 3 (79.3-99.2 nmol/L). A threshold of 75 nmol/L for serum 25-hydroxyvitamin D may represent an intervention target to reduce mortalities in patients with cancer, and maintaining 25(OH)D concentrations within range (79.3-99.2 nmol/L) is beneficial for reducing all-cause and cancer-specific mortality.
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Doenças Cardiovasculares , Neoplasias , Deficiência de Vitamina D , Adulto , Humanos , Inquéritos Nutricionais , Vitamina D , Vitaminas , Calcifediol , Fatores de RiscoRESUMO
The interleukin-12 (IL-12) family is a class of heterodimeric cytokines that play crucial roles in pro-inflammatory and pro-stimulatory responses. Although some IL-12 and IL-23 paralogues have been found in fish, their functional activity in fish remains poorly understood. In this study, Pf_IL-12p35a/b, Pf_IL-23p19 and Pf_IL-12p40a/b/c genes were cloned from yellow catfish (Pelteobagrus fulvidraco), four α-helices were found in Pf_IL-12p35a/b and Pf_IL-23p19. The transcripts of these six genes were relatively high in mucus and immune tissues of healthy individuals, and in gill leukocytes. Following Edwardsiella ictaluri infection, Pf_IL-12p35a/b and Pf_IL-23p19 mRNAs were induced in brain and kidney (or head kidney), Pf_IL-12p40a mRNA was induced in gill, and Pf_IL-12p40b/c mRNAs were induced in brain and liver (or skin). The mRNA expression of these genes in PBLs was induced by phytohaemagglutinin (PHA) and polyinosinic-polycytidylic acid (poly I:C), while lipopolysaccharides (LPS) induced the mRNA expression of Pf_IL-12p35a and Pf_IL-12p40b/c in PBLs. After stimulation with recombinant (r) Pf_IL-12 and rPf_IL-23 subunit proteins, either alone or in combination, mRNA expression patterns of genes related to T helper cell development exhibited distinct differences. The results suggest that Pf_IL-12 and Pf_IL-23 subunits may play important roles in regulating immune responses to pathogens and T helper cell development.
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Peixes-Gato , Infecções por Enterobacteriaceae , Doenças dos Peixes , Proteínas de Peixes , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Imunidade Inata , Subunidade p40 da Interleucina-12 , Animais , Peixes-Gato/genética , Peixes-Gato/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/veterinária , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Subunidade p40 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/imunologia , Perfilação da Expressão Gênica/veterinária , Imunidade Inata/genética , Edwardsiella ictaluri/fisiologia , Subunidade p35 da Interleucina-12/genética , Subunidade p35 da Interleucina-12/imunologia , Filogenia , Sequência de Aminoácidos , Alinhamento de Sequência/veterinária , Subunidade p19 da Interleucina-23/genética , Subunidade p19 da Interleucina-23/imunologia , Poli I-C/farmacologiaRESUMO
Hydrous ferric arsenate (HFA) is a common thermodynamically metastable phase in acid mine drainage (AMD). However, little is known regarding the structural forms and transformation mechanism of HFA. We investigated the local atomic structures and the crystallization transformation of HFA at various Fe(III)/As(V) ratios (2, 1, 0.5, 0.33, and 0.25) in acidic solutions (pH 1.2 and 1.8). The results show that the Fe(III)/As(V) in HFA decreases with decreasing initial Fe(III)/As(V) at acidic pHs. The degree of protonation of As(V) in HFA increases with increasing As(V) concentrations. The Fe K-edge extended X-ray absorption fine structure and X-ray absorption near-edge structure results reveal that each FeO6 is linked to more than two AsO4 in HFA precipitated at Fe(III)/As(V) < 1. Furthermore, the formation of scorodite (FeAsO4·2H2O) is greatly accelerated by decreasing the initial Fe(III)/As(V). The release of As(V) from HFA is observed during its crystallization transformation process to scorodite at Fe(III)/As(V) < 1, which is different from that at Fe(III)/As(V) ≥ 1. Scanning electron microscopy results show that Oswald ripening is responsible for the coarsening of scorodite regardless of the initial Fe(III)/As(V) or pH. Moreover, the formation of crystalline ferric dihydrogen arsenate as an intermediate phase at Fe(III)/As(V) < 1 is responsible for the enhanced transformation rate from HFA to scorodite. This work provides new insights into the local atomic structure of HFA and its crystallization transformation that may occur in AMD and has important implications for arsenic geochemical cycling.
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OBJECTIVE: The objective of this study is to investigate whether a newly introduced deep learning-based iterative reconstruction algorithm, namely, the artificial intelligence iterative reconstruction (AIIR), has a clinical value in computed tomography angiography (CTA), especially for visualizing vascular structures and related lesions, with routine dose settings. METHODS: A total of 63 patients were retrospectively collected from the triple rule-out CTA examinations, where both pulmonary and aortic data were available for each patient and were taken as the example for investigation. The images were reconstructed using the filtered back projection (FBP), hybrid iterative reconstruction (HIR), and the AIIR. The visibility of vasculature and pulmonary emboli and the general image quality were assessed. RESULTS: Artificial intelligence iterative reconstruction resulted in significantly ( P < 0.001) lower noise as well as higher signal-to-noise ratio and contrast-to-noise ratio compared with FBP and HIR. Besides, AIIR achieved the highest subjective scores on general image quality ( P < 0.05). For the vasculature visibility, AIIR offered the best vessel conspicuity, especially for the small vessels ( P < 0.05). Also, >90% of emboli on the AIIR images were graded as sharp (score 5), whereas <15% of emboli on FBP and HIR images were scored 5. CONCLUSION: As demonstrated for pulmonary and aortic CTAs, AIIR improves the image quality and offers a better depiction for vascular structures compared with FBP and HIR. The visibility of the pulmonary emboli was also increased by AIIR.
Assuntos
Angiografia por Tomografia Computadorizada , Embolia Pulmonar , Humanos , Angiografia por Tomografia Computadorizada/métodos , Inteligência Artificial , Artéria Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Aorta , Embolia Pulmonar/diagnóstico por imagem , Algoritmos , Doses de RadiaçãoRESUMO
BACKGROUND: To further clarify the acne profile of Chinese adult women, we included 1,156,703 adult women. An artificial intelligence algorithm was used to analyze images taken by high-resolution mobile phones to further explore acne levels in Chinese adult women. METHOD: In this study, we assessed the severity of acne by evaluating patients' selfies through a smartphone application. Furthermore, we gathered basic user information through a questionnaire, including details such as age, gender, skin sensitivity, and dietary habits. RESULTS: This study showed a gradual decrease in acne severity from the age of 25 years. A trough was reached between the ages of 40 and 44, followed by a gradual increase in acne severity. In terms of skin problems and acne severity, we have found that oily skin, hypersensitive skin, frequent makeup application and unhealthy dietary habits can affect the severity of acne. For environment and acne severity, we observed that developed city levels, cold seasons and high altitude and strong radiation affect acne severity in adult women. For the results of the AI analyses, the severity of blackheads, pores, dark circles and skin roughness were positively associated with acne severity in adult women. CONCLUSIONS: AI analysis of high-res phone images in Chinese adult women reveals acne severity trends. Severity decreases after 25, hits a low at 40-44, then gradually rises. Skin type, sensitivity, makeup, diet, urbanization, seasons, altitude, and radiation impact acne. Blackheads, pores, dark circles, and skin roughness are linked to acne severity. These findings inform personalized skincare and public health strategies for adult women.