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Tea, one of the most widely consumed beverages globally, exhibits remarkable genomic diversity in its underlying flavour and health-related compounds. In this study, we present the construction and analysis of a tea pangenome comprising a total of 11 genomes, with a focus on three newly sequenced genomes comprising the purple-leaved assamica cultivar "Zijuan", the temperature-sensitive sinensis cultivar "Anjibaicha" and the wild accession "L618" whose assemblies exhibited excellent quality scores as they profited from latest sequencing technologies. Our analysis incorporates a detailed investigation of transposon complement across the tea pangenome, revealing shared patterns of transposon distribution among the studied genomes and improved transposon resolution with long read technologies, as shown by long terminal repeat (LTR) Assembly Index analysis. Furthermore, our study encompasses a gene-centric exploration of the pangenome, exploring the genomic landscape of the catechin pathway with our study, providing insights on copy number alterations and gene-centric variants, especially for Anthocyanidin synthases. We constructed a gene-centric pangenome by structurally and functionally annotating all available genomes using an identical pipeline, which both increased gene completeness and allowed for a high functional annotation rate. This improved and consistently annotated gene set will allow for a better comparison between tea genomes. We used this improved pangenome to capture the core and dispensable gene repertoire, elucidating the functional diversity present within the tea species. This pangenome resource might serve as a valuable resource for understanding the fundamental genetic basis of traits such as flavour, stress tolerance, and disease resistance, with implications for tea breeding programmes.
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Camellia sinensis , Elementos Transponibles de ADN , Genoma de Planta , Camellia sinensis/genética , Genoma de Planta/genética , Elementos Transponibles de ADN/genética , Variación Genética , Té/genética , Genómica , Catequina/genéticaRESUMEN
The testis-specific adenosine deaminase domain-containing (ADAD) protein family, including ADAD1 and ADAD2, has been confirmed to be essential in mouse male fertility. However, the roles of ADAD1 and ADAD2 in human reproductive biology are unclear. Herein, whole-exome sequencing was conducted for 337 infertile patients to detect pathogenic variants in ADAD1 and ADAD2. Importantly, a novel deleterious biallelic variant of NM_001159285.2:c.1408G > T (p.V470F) and NM_001159285.2:c.1418A > G (p.E473G) in ADAD1 and a pathogenic homozygous missense variant of NM_001145400.2:c.1381C > T (p.R461W) in ADAD2 were identified in this infertile cohort with frequencies of 0.29 (1/337) and 0.59% (2/337), respectively. Electron microscopy revealed an abnormal morphology and severely disorganized ultrastructure of sperm from the patients. Immunofluorescence and western blotting showed a sharp decrease in ADAD1 and ADAD2 expression in sperm from the patients. Mechanistically, bioinformatics analysis suggested that ADAD2 interacts with DNAH17. Furthermore, we demonstrated that the expression of DNAH17 was markedly downregulated in the sperm of patients harboring ADAD2 variants. In addition, the expression of several autophagy regulators was significantly disrupted in the sperm of patients harboring ADAD2 variants. In conclusion, we identified novel ADAD1 and ADAD2 variants in three infertile patients from a large infertile cohort, first providing evidence that ADAD1 and ADAD2 variants might be a candidate genetic cause of human male infertility. Moreover, an important new dimension to our understanding of the genotype-phenotype correlations between the ADAD gene family and male infertility in humans has been uncovered, providing valuable information for the genetic diagnosis of male infertility.
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Adenosina Desaminasa , Infertilidad Masculina , Humanos , Masculino , Animales , Ratones , Adenosina Desaminasa/genética , Testículo/patología , Semen , Infertilidad Masculina/genética , Infertilidad Masculina/patología , Espermatozoides , Mutación Missense/genética , Espermatogénesis/genéticaRESUMEN
This study addresses the challenge of designing simple and environmentally friendly methods for the preparation of effective electromagnetic wave (EMW) absorbing materials with tailored microstructures and multi-component regulation. N, O doped walnut-like porous carbon composite microspheres loaded with FeCo nanoparticles (WPCM/Fe-Co) are synthesized through high-temperature carbonization combined with soap-free emulsion polymerization and hydrothermal methods, avoiding the use of toxic solvents and complex conditions. The incorporation of magnetic components enhances magnetic loss, complementing dielectric loss to optimize EMW attenuation. The unique walnut-like morphology further improves impedance matching. The proportions of Fe and Co components can be adjusted to regulate the material's reflection loss, thickness, and bandwidth, allowing for fine-tuning of absorption performance. At a low filling ratio (16.7%), the optimal WPCM/Fe-Co composites exhibit a minimum reflection loss (RLmin) of -48.34 dB (10.33 GHz, 3.0 mm) and an overall effective absorbing bandwidth (EAB) covering the entire C bands, X bands, and Ku bands. This work introduces a novel approach to composition regulation and presents a green synthesis method for magnetic carbon composite absorbers with high-performance EMW absorption at low loading.
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As a frequently consumed beverage worldwide, tea is rich in naturally important bioactive metabolites. Combining genetic, metabolomic and biochemical methodologies, here, we present a comprehensive study to dissect the chemical diversity in tea plant. A total of 2837 metabolites were identified at high-resolution with 1098 of them being structurally annotated and 63 of them were structurally identified. Metabolite-based genome-wide association mapping identified 6199 and 7823 metabolic quantitative trait loci (mQTL) for 971 and 1254 compounds in young leaves (YL) and the third leaves (TL), respectively. The major mQTL (i.e., P < 1.05 × 10-5, and phenotypic variation explained (PVE) > 25%) were further interrogated. Through extensive annotation of the tea metabolome as well as network-based analysis, this study broadens the understanding of tea metabolism and lays a solid foundation for revealing the natural variations in the chemical composition of the tea plant. Interestingly, we found that galloylations, rather than hydroxylations or glycosylations, were the largest class of conversions within the tea metabolome. The prevalence of galloylations in tea is unusual, as hydroxylations and glycosylations are typically the most prominent conversions of plant specialized metabolism. The biosynthetic pathway of flavonoids, which are one of the most featured metabolites in tea plant, was further refined with the identified metabolites. And we demonstrated the further mining and interpretation of our GWAS results by verifying two identified mQTL (including functional candidate genes CsUGTa, CsUGTb, and CsCCoAOMT) and completing the flavonoid biosynthetic pathway of the tea plant.
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Camellia sinensis , Estudio de Asociación del Genoma Completo , Metaboloma/genética , Metabolómica , Sitios de Carácter Cuantitativo/genética , Flavonoides/genética , Flavonoides/metabolismo , Camellia sinensis/genética , Té/genética , Té/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismoRESUMEN
LincRNA-EPS is an important regulator in inflammation. However, the role of lincRNA-EPS in the host response against viral infection is unexplored. Here, we show that lincRNA-EPS is downregulated in macrophages infected with different viruses including VSV, SeV, and HSV-1. Overexpression of lincRNA-EPS facilitates viral infection, while deficiency of lincRNA-EPS protects the host against viral infection in vitro and in vivo. LincRNA-EPS-/- macrophages show elevated expression of antiviral interferon-stimulated genes (ISGs) such as Mx1, Oas2, and Ifit2 at both basal and inducible levels. However, IFN-ß, the key upstream inducer of these ISGs, is downregulated in lincRNA-EPS-/- macrophages compared with control cells. RNA pulldown and mass spectrometry results indicate that lincRNA-EPS binds to PKR and antagonizes the viral RNA-PKR interaction. PKR activates STAT1 and induces antiviral ISGs independent of IFN-I induction. LincRNA-EPS inhibits PKR-STAT1-ISGs signaling and thus facilitates viral infection. Our study outlines an alternative antiviral pathway, with downregulation of lincRNA-EPS promoting the induction of PKR-STAT1-dependent ISGs, and reveals a potential therapeutic target for viral infectious diseases.
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ARN Largo no Codificante , Antivirales , Inmunidad Innata , Interferón beta/genética , Interferones , ARN Largo no Codificante/genética , ARN Viral/metabolismoRESUMEN
Solid-state contact ion-selective electrodes (SC-ISEs) are an efficacious means of monitoring heavy metal contamination. Instability of the electrode potential is a key factor limiting their development, with biofouling in real water samples posing a significant challenge to maintaining stability. Therefore, addressing biofouling is crucial for optimizing solid-state ion-selective electrodes. In this work, high stability and antibiofouling capability in a solid-state contact lead ion-selective electrode (SC-Pb2+-ISE) based on polyaniline (PANI) was achieved through cathodic polarization. Specifically, PANI played a dual role in the ion-selective membrane (ISM) as an ion-to-electron transducer and antifouling agent. Given the excellent electrochemical performance of PANI, the prepared electrode (GC/PANI-Pb2+-ISM) demonstrated a remarkable antibiofouling efficiency of 98.2% under a cathodic polarization of -0.2 V. Furthermore, a standard deviation of standard potential (Eθ) as low as ± 0.5 mV was realized successfully. The excellent chrono-potentiometric stability of 17.0 ± 2.9 µV/s was also demonstrated. The electrode maintained a Nernstian response slope of 30.7 ± 0.2 (R2 = 0.998) after applying a cathode potential (-0.2 V) for 30 min. The developed GC/PANI-Pb2+-ISM electrode is suitable for practical applications in real environmental water sample monitoring.
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Horticultural crops mainly include fruits, vegetables, ornamental trees and flowers, and tea trees (Melaleuca alternifolia). They produce a variety of nutrients for the daily human diet in addition to the nutrition provided by staple crops, and some of them additionally possess ornamental and medicinal features. As such, horticultural crops make unique and important contributions to both food security and a colorful lifestyle. Under the current climate change scenario, the growing population and limited arable land means that agriculture, and especially horticulture, has been facing unprecedented challenges to meet the diverse demands of human daily life. Breeding horticultural crops with high quality and adaptability and establishing an effective system that combines cultivation, post-harvest handling, and sales becomes increasingly imperative for horticultural production. This review discusses characteristic and recent research highlights in horticultural crops, focusing on the breeding of quality traits and the mechanisms that underpin them. It additionally addresses challenges and potential solutions in horticultural production and post-harvest practices. Finally, we provide a prospective as to how emerging technologies can be implemented alongside interdisciplinary basic research to enhance our understanding and exploitation of horticultural crops.
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Inteligencia Artificial , Bioingeniería , Biología Computacional , Productos Agrícolas , Horticultura , Cambio Climático , Flores , Frutas , Investigación Interdisciplinaria , Nutrientes , Fitomejoramiento , Árboles , VerdurasRESUMEN
XIAP-associated factor 1 (XAF1) is an interferon (IFN)-stimulated gene (ISG) that enhances IFN-induced apoptosis. However, it is unexplored whether XAF1 is essential for the host fighting against invaded viruses. Here, we find that XAF1 is significantly upregulated in the host cells infected with emerging RNA viruses, including influenza, Zika virus (ZIKV), and SARS-CoV-2. IFN regulatory factor 1 (IRF1), a key transcription factor in immune cells, determines the induction of XAF1 during antiviral immunity. Ectopic expression of XAF1 protects host cells against various RNA viruses independent of apoptosis. Knockout of XAF1 attenuates host antiviral innate immunity in vitro and in vivo, which leads to more severe lung injuries and higher mortality in the influenza infection mouse model. XAF1 stabilizes IRF1 protein by antagonizing the CHIP-mediated degradation of IRF1, thus inducing more antiviral IRF1 target genes, including DDX58, DDX60, MX1, and OAS2. Our study has described a protective role of XAF1 in the host antiviral innate immunity against RNA viruses. We have also elucidated the molecular mechanism that IRF1 and XAF1 form a positive feedback loop to induce rapid and robust antiviral immunity. IMPORTANCE Rapid and robust induction of antiviral genes is essential for the host to clear the invaded viruses. In addition to the IRF3/7-IFN-I-STAT1 signaling axis, the XAF1-IRF1 positive feedback loop synergistically or independently drives the transcription of antiviral genes. Moreover, XAF1 is a sensitive and reliable gene that positively correlates with the viral infection, suggesting that XAF1 is a potential diagnostic marker for viral infectious diseases. In addition to the antitumor role, our study has shown that XAF1 is essential for antiviral immunity. XAF1 is not only a proapoptotic ISG, but it also stabilizes the master transcription factor IRF1 to induce antiviral genes. IRF1 directly binds to the IRF-Es of its target gene promoters and drives their transcriptions, which suggests a unique role of the XAF1-IRF1 loop in antiviral innate immunity, particularly in the host defect of IFN-I signaling such as invertebrates.
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Proteínas Adaptadoras Transductoras de Señales , Proteínas Reguladoras de la Apoptosis , Factor 1 Regulador del Interferón , Infecciones por Virus ARN , Virus ARN , Proteínas Adaptadoras Transductoras de Señales/inmunología , Animales , Proteínas Reguladoras de la Apoptosis/inmunología , Humanos , Inmunidad Innata , Factor 1 Regulador del Interferón/inmunología , Ratones , Ratones Noqueados , Infecciones por Virus ARN/inmunología , Replicación ViralRESUMEN
BACKGROUND: Radiosensitivity of rectal cancer is related to the radiotherapy efficacy and prognosis of patients with rectal cancer, and the genes and molecular mechanisms related to radiosensitivity of rectal cancer have not been clarified. We explored the radiosensitivity related genes of rectal cancer at a multi omics level. METHODS: mRNA expression data and rectum adenocarcinoma (READ) data were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus Database (GEO) (GSE150082, GSE60331, GSE46862, GSE46862). Differentially expressed genes between radiotherapy sensitive group and radiotherapy insensitive group were screened. GO analysis and KEGG pathway analysis were performed for differentially expressed genes. Among the differentially expressed genes, five core genes associated with rectal cancer prognosis were selected using random survival forest analysis. For these five core genes, drug sensitivity analysis, immune cell infiltration analysis, TISIDB database immune gene correlation analysis, GSEA enrichment analysis, construction of Nomogram prediction model, transcriptional regulatory network analysis, and qRT-PCR validation was performed on human rectal adenocarcinoma tissue. RESULTS: We found that 600 up-regulated genes and 553 down-regulated genes were significantly different between radiotherapy sensitive group and radiotherapy insensitive group in rectal cancer. Five key genes, TOP2A, MATR3, APOL6, JOSD1, and HOXC6, were finally screened by random survival forest analysis. These five key genes were associated with different immune cell infiltration, immune-related genes, and chemosensitivity. A comprehensive transcriptional regulatory network was constructed based on these five core genes. qRT-PCR revealed that MATR3 expression was different in rectal cancer tissues and adjacent non-cancerous tissues, while APOL6, HOXC6, JOSD1, and TOP2A expression was not different. CONCLUSION: Five radiosensitivity-related genes related to the prognosis of rectal cancer: TOP2A, MATR3, APOL6, JOSD1, HOXC6, are involved in multiple processes such as immune cell infiltration, immune-related genes, chemosensitivity, signaling pathways and transcriptional regulatory networks and may be potential biomarkers for radiotherapy of rectal cancer.
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Adenocarcinoma , Neoplasias del Recto , Humanos , Pronóstico , Multiómica , Neoplasias del Recto/genética , Neoplasias del Recto/radioterapia , Mapeo Cromosómico , Proteínas de Unión al ARN , Proteínas Asociadas a Matriz NuclearRESUMEN
The optic nerve (ON) can get compressed in different diseases. However, the pathological and functional changes occurring in the compressed ON over time under constant compression are still unclear. In the present study, we implanted an artificial tube around the optic nerve of a rabbit to primarily create a clinically relevant persistent compressive optic nerve axonopathy (PCOA). Due to the protuberance on the inner ring of the tube, steady and persistent compressions were maintained. In this model, we investigated the thickness of ganglion cell complex (GCC), retinal ganglion cell (RGC) density, axon density of optic nerve, flash visual evoked potential (FVEP), and anterograde axonal transport at various times in four different groups viz. the no comp, 1/2 comp, 3/4 comp, and crush groups. The GCC thickness, RGC density, and axon density of ON were hierarchically and significantly decreased in 1/2 comp, 3/4 comp, and crush groups. Compared to no comp eyes, the P2 amplitude ratio of FVEP was significantly decreased in 3/4 comp but not in 1/2 comp eyes. Only a portion of the optic nerve lost the ability of anterograde axonal transport in the 1/2 comp group. However, it was evident at 2-wpo and more prominent at 4-wpo in 3/4 comp eyes. This study reveals that the compression only induces the homolateral ON axons impairment and the proportion of the affected axons maintains the same for mild compression for at least three months. Furthermore, an underlying threshold effect highlights that mild compression does not require urgent surgery, while the severe compression warrants immediate surgical intervention.
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Enfermedades del Nervio Óptico , Traumatismos del Nervio Óptico , Animales , Conejos , Potenciales Evocados Visuales , Nervio Óptico/patología , Células Ganglionares de la Retina/patología , Enfermedades del Nervio Óptico/patología , Traumatismos del Nervio Óptico/patología , Axones/patología , Compresión Nerviosa , Modelos Animales de EnfermedadRESUMEN
Populus euphratica and Tamarix chinensis play a vital role in windbreak and sand fixation, maintaining species diversity and ensuring community stability. Managing and protecting the P. euphratica and T. chinensis forests in the Heihe River's lower reaches is an urgent issue to maintain the desert region's ecological balance. In this study, based on the distribution points of P. euphratica and T. chinensis species and environmental data, MaxEnt and random forest (RF) models were used to characterize the potential distribution areas of P. euphratica and T. chinensis in the lower reaches of the Heihe River. The results showed that the accuracy of the RF model was much higher than that of the MaxEnt model. Both the RF and MaxEnt models showed that the distance to the river greatly influenced the distribution of P. euphratica and T. chinensis. Furthermore, the RF model predicted significantly larger highly suitable areas for both P. euphratica and T. chinensis than the MaxEnt model. Our study enhances the understanding of the species' spatial distribution, offering valuable insights for practical management and conservation strategies.
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Populus , Tamaricaceae , Ríos , Bosques Aleatorios , Monitoreo del Ambiente , ChinaRESUMEN
BACKGROUND: In 2014, the American Academy of Pediatrics stopped recommending palivizumab to otherwise healthy 29-34 weeks' gestational age (wGA) infants aged <12 months at respiratory syncytial virus (RSV) season start. Here, we compare the burden of RSV hospitalizations (RSVH) and all-cause bronchiolitis hospitalizations (BH) before and after 2014 among otherwise healthy 29-34 wGA infants hospitalized at ≤6 months of age. METHODS: A historical, observational cohort study was conducted to evaluate RSVH and BH in 29-34 wGA infants during the 2010-2017 RSV seasons using encounter data from 51 United States children's hospitals that comprise the Pediatric Health Information System. RESULTS: The overall cohort included 67 570 RSVH out of 96 281 patients with BH. wGA was known for 22 937 RSVH and 33 289 BH. For 29-34 wGA infants, there were 8.7% and 14.2% RSVH before and after 2014, respectively (P < .0001). Intensive care unit admissions increased for RSVH (from 54.5% to 64.2%; P = .0002) and BH (from 46.7% to 54.5%; P = .0005) after controlling for sex, race, comorbidity, and cluster. The total cost of care increased for RSVH from $37 million to nearly $60 million. CONCLUSIONS: RSVH, BH, and their severity increased among 29-34 wGA infants in the 3 RSV seasons following 2014.
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Bronquiolitis , Sistemas de Información en Salud , Pediatría , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Antivirales/uso terapéutico , Bronquiolitis/epidemiología , Niño , Edad Gestacional , Hospitalización , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/epidemiología , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: This study describes leading causes of hospitalization, including respiratory syncytial virus (RSV), in United States infants (<1 year) from 2009 through 2019. METHODS: Within the National (Nationwide) Inpatient Sample (NIS) data, hospitalizations were determined by primary diagnosis using International Classification of Diseases, Ninth or Tenth Revision codes. RSV was defined as 079.6, 466.11, 480.1, B97.4, J12.1, J20.5, or J21.0. Bronchiolitis was defined as 466.19, J21.8, or J21.9. Leading causes overall and by sociodemographic variables were identified. The Kids' Inpatient Database (KID) was used for confirmatory analyses. RESULTS: Acute bronchiolitis due to RSV (code 466.11 or J21.0) was the leading primary diagnosis, accounting for 9.6% (95% confidence interval [CI], 9.4%-9.9%) and 9.3% (95% CI, 9.0%-9.6%) of total infant hospitalizations from January 2009 through September 2015 and October 2015 through December 2019, respectively; it was the leading primary diagnosis in every year accounting for >10% of total infant hospitalizations from December through March, reaching >15% in January-February. From 2009 through 2011, acute bronchiolitis due to RSV was the leading primary diagnosis in every birth month. Acute bronchiolitis due to RSV was the leading cause among all races/ethnicities, except Asian/Pacific Islanders, and all insurance payer groups. KID analyses confirmed these results. CONCLUSIONS: Acute bronchiolitis due to RSV is the leading cause of US infant hospitalizations.
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Bronquiolitis , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Bronquiolitis/epidemiología , Hospitalización , Humanos , Lactante , Pacientes Internos , Infecciones por Virus Sincitial Respiratorio/epidemiología , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Infant mortality due to respiratory syncytial virus (RSV) in the United States is not well understood. METHODS: From 1999 to 2018, RSV, bronchiolitis, and influenza deaths were described for infants <1 year using linked birth/death datasets from the National Vital Statistics System. Mortality was described overall and by infant birth and death characteristics. Bronchiolitis was included as the plausible upper limit of RSV, while influenza served as a comparator. RESULTS: Total infant deaths were 561 RSV, 1603 bronchiolitis, and 504 influenza, and rates were 6.9 (95% confidence interval [CI], 6.4-7.5), 19.8 (95% CI, 18.9-20.8), and 6.2 (95% CI, 5.7-6.8) per 1 000 000 live births, respectively. The highest RSV rates were observed among <29 weeks' gestational age infants (103.5; 95% CI, 81.8-129.1), American Indian/Alaskan Native (20.3; 95% CI, 11.6-33.0), and Medicaid-insured (7.3; 95% CI, 5.9-8.9). However, RSV mortality burden was greatest in full-term (53.7%), white (44.9%), and Medicaid-insured (61.7%) infants. Deaths outside the inpatient setting were 21% and 54% for RSV and bronchiolitis; more Medicaid- (58%) and other/unknown-insured (69%) infants with bronchiolitis died outside of the inpatient setting, compared to privately insured infants (48%) (P = .0327). CONCLUSIONS: These national estimates emphasize the importance of considering all infants across all healthcare settings when describing RSV mortality.
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Bronquiolitis , Gripe Humana , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Cohorte de Nacimiento , Bronquiolitis/complicaciones , Bronquiolitis/epidemiología , Estudios de Cohortes , Humanos , Lactante , Gripe Humana/complicaciones , Infecciones por Virus Sincitial Respiratorio/complicaciones , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of hospitalizations in United States infants aged <1 year, but research has focused on select populations. METHODS: National (Nationwide) Inpatient Sample and National Emergency Department (ED) Sample data (2011-2019) were used to report RSV hospitalization (RSVH), bronchiolitis hospitalization (BH), and ED visit counts, percentage of total hospitalizations/visits, and rates per 1000 live births along with inpatient mortality, mechanical ventilation (MV), and total charges (2020 US dollars). RESULTS: Average annual RSVH and RSV ED visits were 56 927 (range, 43 845-66 155) and 131 999 (range, 89 809-177 680), respectively. RSVH rates remained constant over time (P = .5), whereas ED visit rates increased (P = .004). From 2011 through 2019, Medicaid infants had the highest average rates (RSVH: 22.3 [95% confidence interval {CI}, 21.5-23.1] per 1000; ED visits: 55.9 [95% CI, 52.4-59.4] per 1000) compared to infants with private or other/unknown insurance (RSVH: P < .0001; ED visits: P < .0001). From 2011 through 2019, for all races and ethnicities, Medicaid infants had higher average RSVH rates (up to 7 times) compared to infants with private or other/unknown insurance. RSVH mortality remained constant over time (P = .8), whereas MV use (2019: 13% of RSVH, P < .0001) and mean charge during hospitalization (2019: $21 513, P < .0001) increased. Bronchiolitis patterns were similar. CONCLUSIONS: This study highlights the importance of ensuring access to RSV preventive measures for all infants.
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Bronquiolitis , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Bronquiolitis/epidemiología , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Aceptación de la Atención de Salud , Estados Unidos/epidemiologíaRESUMEN
Gastric cancer ranked third worldwide in terms of mortality. The immediate priority is to search for new prognosticative or therapeutic targets. This research aims to examine the function of the NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) in the malignant phenotype of gastric carcinoma. We analyzed the correlation between NDUFS4 expression and gastric cancer via bioinformatics analysis and cancer tissue microarray via immunohistochemistry. Also, we detected the phenotype change in gastric cancer cells after NDUFS4 was downregulated. NDUFS4's high expression in gastric cancer tissues showed an association with terminal TNM stage and unfavorable survival. Furthermore, downregulation of NDUFS4 decreased gastric cancer cell proliferation, migration and invasion. Nude mouse models revealed that NDUFS4 promotes tumor growth. This investigation highlights the prognostic role of NDUFS4 in gastric cancer. Our results also creatively ascertained NDUFS4 as a candidate for gastric cancer therapeutic targets.
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Neoplasias Gástricas , Ratones , Animales , Neoplasias Gástricas/patología , Movimiento Celular/genética , Proliferación Celular/genética , Pronóstico , Inmunohistoquímica , Ratones Desnudos , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Complejo I de Transporte de Electrón/genética , Complejo I de Transporte de Electrón/metabolismoRESUMEN
BACKGROUND: Targeting glutamine metabolism is previously indicated as a potential and attractive strategy for gastric cancer (GC) therapy. However, the underlying mechanisms responsible for the modification of glutamine metabolism in GC cells have not been fully elucidated. Accordingly, the current study sought to investigate the physiological mechanisms of RUNX3-mediated circDYRK1A in glutamine metabolism of GC. METHODS: Firstly, GC tissues and adjacent normal tissues were obtained from 50 GC patients to determine circDYRK1A expression in GC tissues. Next, the binding affinity among RUNX3, circDYRK1A, miR-889-3p, and FBXO4 was detected to clarify the mechanistic basis. Moreover, GC cells were subjected to ectopic expression and knockdown manipulations of circDYRK1A, miR-889-3p, and/or FBXO4 to assay GC cell malignant phenotypes, levels of glutamine, glutamic acid, and α-KG in cell supernatant and glutamine metabolism-related proteins (GLS and GDH). Finally, nude mice were xenografted with GC cells to explore the in vivo effects of circDYRK1A on the tumorigenicity and apoptosis. RESULTS: circDYRK1A was found to be poorly expressed in GC tissues. RUNX3 was validated to bind to the circDYRK1A promoter, and circDYRK1A functioned as a miR-889-3p sponge to up-regulate FBXO4 expression. Moreover, RUNX3-upregulated circDYRK1A reduced levels of glutamine, glutamic acid, and α-KG, and protein levels of GLS and GDH, and further diminished malignant phenotypes in vitro. Furthermore, in vivo experimentation substantiated that circDYRK1A inhibited the tumorigenicity and augmented the apoptosis in GC. CONCLUSION: In conclusion, these findings highlighted the significance and mechanism of RUNX3-mediated circDYRK1A in suppressing glutamine metabolism in GC via the miR-889-3p/FBXO4 axis.
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Proteínas F-Box , MicroARNs , Neoplasias Gástricas , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Regulación Neoplásica de la Expresión Génica , Glutamina/metabolismo , Humanos , Ratones , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia mediated by immunoglobulin M autoantibodies that bind to the "I" antigen on erythrocytes. IgM binding results in either agglutination at ≤37°C, activation of the classical complement pathway, or both. Patients with CAD can have transient agglutination-mediated circulatory symptoms triggered by exposure to cold conditions. Separately, patients with CAD can experience complement-mediated symptoms such as anemia, hemolysis, and fatigue, but the effect of the season on these complement-mediated manifestations of CAD and clinical outcomes is not well understood. METHODS: Using data from the Optum® de-identified Electronic Health Record dataset, we compared hemoglobin, markers of hemolysis (bilirubin and lactate dehydrogenase [LDH]), and healthcare resource utilization (HRU) between seasons for 594 patients (62% female; 66% aged ≥65 years) with CAD (defined as having CAD-related terms in their clinical notes on ≥3 separate occasions between December 2008 and May 2016). Laboratory parameters and HRU were compared between seasons using multivariate regression models. RESULTS: Estimated median hemoglobin (9.87 g/dL in summer and 9.86 g/dL in winter; P = 0.944) and bilirubin (1.04 mg/dL in summer and 1.09 mg/dL in winter; P = 0.257) were similar in winter versus summer. While LDH was statistically significantly higher in winter compared with summer (P < 0.001), the estimated median value was above normal for both seasons (309 U/L in summer and 367 U/L in winter). HRU measures and transfusion and thromboembolism rates were similar across seasons. CONCLUSIONS: Patients with CAD had evidence of persistent chronic hemolysis, HRU, and thromboembolism risk year round.
Asunto(s)
Anemia Hemolítica Autoinmune , Tromboembolia , Bilirrubina , Proteínas del Sistema Complemento , Femenino , Hemólisis , Humanos , L-Lactato Deshidrogenasa , MasculinoRESUMEN
Long-term and green marine antifouling coatings are an important means to prolong the service life of ships and other marine instruments and equipment. To accomplish this, we prepared three new green and high-efficiency antifouling coatings containing phthalimide derivatives inspired by capsaicin (PDIC-AC) by using a collaborative strategy that incorporates self-polishing, fouling repelling, and antifouling properties. Static simulation tests confirmed that the zinc acrylate resin of the PDIC-AC has excellent self-polishing properties due to changes in the roughness, surface free energy, and mass loss. Antifouling tests demonstrated that both PDIC and PDIC-AC possess efficient antibacterial and anti-algal effects. Moreover, marine field tests showed that the PDIC-AC are highly antifouling for at least 9 months, and their antifouling effect is similar to that of an antifouling coating with chlorothalonil (CT-AC). The collaborative strategy in this study can be used to research and develop long-term environmentally friendly antifouling coatings.
Asunto(s)
Incrustaciones Biológicas , Antibacterianos , Incrustaciones Biológicas/prevención & control , Propiedades de SuperficieRESUMEN
The evidence from many studies shows that antifoulants (Cu2O) and organic antifouling agents with broad-spectrum characteristics in antifouling coatings cause varying degrees of damage to the environment. Therefore, this study prepared Cu2O-free self-polishing antifouling coatings based on amide derivatives inspired by capsaicin (ADIC-CSAC) with green and environmentally friendly characteristics. First, the structure of ADIC and the composition of ADIC-CSAC were characterized by IR, 1H NMR, 13C NMR, HRMS, and EDX. Moreover, antibacterial, anti-algal, static raft tests and changes in the mass loss, roughness, contact angle, and surface energy were used to evaluate the antifouling and self-polishing properties of ADIC-CSAC. The test results showed that ADIC and ADIC-CSAC were successfully prepared and ADIC-CSAC possessed good antifouling and self-polishing properties. ADIC-CSAC exhibited antibacterial and anti-algal rates of over 88 and 72%, respectively, and was found to have satisfactory antifouling properties over 9 months in a real marine field. Overall, the prepared ADIC-CSAC possesses good and green antifouling and self-polishing properties, which lays a foundation for research on green antifouling coatings used for environmental protection.