RESUMEN
Soybean is one of the most important vegetable oil and protein feed crops. To capture the entire genomic diversity, it is needed to construct a complete high-quality pan-genome from diverse soybean accessions. In this study, we performed individual de novo genome assemblies for 26 representative soybeans that were selected from 2,898 deeply sequenced accessions. Using these assembled genomes together with three previously reported genomes, we constructed a graph-based genome and performed pan-genome analysis, which identified numerous genetic variations that cannot be detected by direct mapping of short sequence reads onto a single reference genome. The structural variations from the 2,898 accessions that were genotyped based on the graph-based genome and the RNA sequencing (RNA-seq) data from the representative 26 accessions helped to link genetic variations to candidate genes that are responsible for important traits. This pan-genome resource will promote evolutionary and functional genomics studies in soybean.
Asunto(s)
Genoma de Planta , Glycine max/crecimiento & desarrollo , Glycine max/genética , Secuencia de Bases , Cromosomas de las Plantas/genética , Domesticación , Ecotipo , Duplicación de Gen , Regulación de la Expresión Génica de las Plantas , Fusión Génica , Geografía , Anotación de Secuencia Molecular , Filogenia , Polimorfismo de Nucleótido Simple/genética , PoliploidíaRESUMEN
Pathogens have co-evolved with mosquitoes to optimize transmission to hosts. Mosquito salivary-gland extract is known to modulate host immune responses and facilitate pathogen transmission, but the underlying molecular mechanisms of this have remained unknown. In this study, we identified and characterized a prominent 15-kilodalton protein, LTRIN, obtained from the salivary glands of the mosquito Aedes aegypti. LTRIN expression was upregulated in blood-fed mosquitoes, and LTRIN facilitated the transmission of Zika virus (ZIKV) and exacerbated its pathogenicity by interfering with signaling through the lymphotoxin-ß receptor (LTßR). Mechanically, LTRIN bound to LTßR and 'preferentially' inhibited signaling via the transcription factor NF-κB and the production of inflammatory cytokines by interfering with the dimerization of LTßR during infection with ZIKV. Furthermore, treatment with antibody to LTRIN inhibited mosquito-mediated infection with ZIKV, and abolishing LTßR potentiated the infectivity of ZIKV both in vitro and in vivo. This study provides deeper insight into the transmission of mosquito-borne diseases in nature and supports the therapeutic potential of inhibiting the action of LTRIN to disrupt ZIKV transmission.
Asunto(s)
Aedes/virología , Proteínas de Insectos/metabolismo , Saliva/metabolismo , Infección por el Virus Zika/transmisión , Virus Zika/patogenicidad , Animales , Humanos , Receptor beta de Linfotoxina/inmunología , Receptor beta de Linfotoxina/metabolismo , Ratones , Mosquitos Vectores/química , Mosquitos Vectores/inmunología , Mosquitos Vectores/metabolismo , Saliva/químicaRESUMEN
Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan-Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late-stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.
Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Ciclo Celular , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , División Celular , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Neoplasias Pulmonares/genética , Regulación hacia Arriba/genéticaRESUMEN
BACKGROUND: The era of high throughput sequencing offers new paths to identifying species boundaries that are complementary to traditional morphology-based delimitations. De novo species delimitation using traditional or DNA super-barcodes serve as efficient approaches to recognizing putative species (molecular operational taxonomic units, MOTUs). Tea plants (Camellia sect. Thea) form a group of morphologically similar species with significant economic value, providing the raw material for tea, which is the most popular nonalcoholic caffeine-containing beverage in the world. Taxonomic challenges have arisen from vague species boundaries in this group. RESULTS: Based on the most comprehensive sampling of C. sect. Thea by far (165 individuals of 39 morphospecies), we applied three de novo species delimitation methods (ASAP, PTP, and mPTP) using plastome data to provide an independent evaluation of morphology-based species boundaries in tea plants. Comparing MOTU partitions with morphospecies, we particularly tested the congruence of MOTUs resulting from different methods. We recognized 28 consensus MOTUs within C. sect. Thea, while tentatively suggesting that 11 morphospecies be discarded. Ten of the 28 consensus MOTUs were uncovered as morphospecies complexes in need of further study integrating other evidence. Our results also showed a strong imbalance among the analyzed MOTUs in terms of the number of molecular diagnostic characters. CONCLUSION: This study serves as a solid step forward for recognizing the underlying species boundaries of tea plants, providing a needed evidence-based framework for the utilization and conservation of this economically important plant group.
Asunto(s)
Camellia sinensis , Camellia , Humanos , Código de Barras del ADN Taxonómico/métodos , Camellia sinensis/genética , Té/genética , ADN , FilogeniaRESUMEN
BACKGROUND: Cardiovascular magnetic resonance (cardiac MR) reference ranges in Chinese children are lacking. PURPOSE: To establish age- and sex-specific reference ranges for cardiac MR parameters in a cohort of healthy Chinese children. STUDY TYPE: Retrospective. SUBJECTS: One hundred ninety-six healthy children (mean age 9.5 ± 3.6 years, 111 boys). FIELD STRENGTH/SEQUENCE: 1.5 T; balanced steady-state free precession. ASSESSMENT: Biventricular volume and ejection fractions (EF), left atrial (LA) volume, right atrial (RA) area, left ventricular (LV) mass and thickness, aortic root (AR), and main pulmonary artery (MPA) dimensions were measured. Parameters were compared between age groups and sex. The relationships between parameters and age, body mass index (BMI) and body surface area (BSA) were investigated. STATISTICAL TESTS: Independent-samples t tests; Pearson's correlation. A P value <0.05 was considered statistically significant. RESULTS: Generally, boys exhibited greater absolute measurements of LV volume (end-diastolic: 94.4 ± 29.5 vs. 81.3 ± 31.0 mL), LA volume (end-diastolic: 42.6 ± 13.4 vs. 38.0 ± 13.3 mL), RA area (end-diastolic: 11.6 ± 2.5 vs. 10.8 ± 2.6 cm2), LV thickness (base: 4.4 ± 1.1 vs. 3.8 ± 0.9 mm), AR dimensions (annuls: 16.3 ± 2.7 vs. 15.0 ± 2.8 mm), and MPA dimensions (14.3 ± 2.3 vs. 13.1 ± 2.4 mm) than girls did. However, these differences were not observed when the measurements were normalized to BSA (LV volume: 75.3 ± 11.7 vs. 71.9 ± 12.3 mL/m2, P = 0.052; LA volume: 34.8 ± 8.9 vs. 34.5 ± 7.6 mL/m2, P = 0.783; RA area: 9.7 ± 2.3 vs. 10.2 ± 2.3 cm2/m2, P = 0.107; LV thickness: 3.6 ± 0.7 vs. 3.6 ± 0.9 mm/m2, P = 0.990; AR: 13.6 ± 2.7 vs. 14.3 ± 3.4 mm/m2, P = 0.108; MPA: 11.9 ± 2.3 vs. 12.4 ± 2.4 mm/m2, P = 0.118). Boys had greater RV volume (end-diastolic: 98.7 ± 33.5 vs. 82.7 ± 33.1 mL) and LV mass (52.6 ± 20.2 vs. 41.4 ± 16.0 g) compared to girls, irrespective of whether the values were indexed or not for BSA. Additionally, there were significant associations between age, BMI, and BSA with biventricular volume, LA volume, RA area, LV mass and thickness, AR and MPA dimensions in both boys and girls. DATA CONCLUSION: This study suggests reference ranges at 1.5 T for Chinese children. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.
RESUMEN
BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.
RESUMEN
This study aims to examine the clinical characteristics and outcomes of clinical myocarditis in pediatric patients in China. This is a multicenter retrospective study. Children diagnosed with clinical myocarditis from 20 hospitals in China and admitted between January 1, 2015, and December 30, 2021, were enrolled. The clinical myocarditis was diagnosed based on the "Diagnostic Recommendation for Myocarditis in Children (Version 2018)". The clinical data were collected from their medical records. A total of 1210 patients were finally enrolled in this study. Among them, 45.6% had a history of respiratory tract infection. An abnormal electrocardiogram was observed in 74.2% of patients. Echocardiography revealed that 32.3% of patients had a left ventricular ejection fraction of less than 50%. Cardiac MRI was performed in 4.9% of children with clinical myocarditis, of which 61% showed localized or diffuse hypersignal on T2-weighted images. Serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal B-type natriuretic peptide (NT-proBNP) were higher in patients with fulminant myocarditis than in patients with myocarditis, making them potential risk factors for fulminant myocarditis. Following active treatment, 12.1% of patients were cured, and 79.1% were discharged with improvement. CONCLUSION: Clinical myocarditis in children often presents with symptoms outside the cardiovascular system. CK-MB, cTnI, and NT-proBNP are important indicators for assessing clinical myocarditis. The electrocardiogram and echocardiogram findings in children with clinical myocarditis exhibit significant variability but lack specificity. Cardiac MRI can be a useful tool for screening clinical myocarditis. Most children with clinical myocarditis have a favorable prognosis. WHAT IS KNOWN: ⢠Pediatric myocarditis presents complex clinical manifestations and exhibits varying degrees of severity. Children with mild myocarditis generally have a favorable prognosis, while a small number of children with critically ill myocarditis experience sudden onset, hemodynamic disorders, and fatal arrhythmias. Therefore, early diagnosis and timely treatment of myocarditis are imperative. WHAT IS NEW: ⢠To the best of our knowledge, this multicenter retrospective study is the largest ever reported in China, aiming to reveal the clinical characteristics and outcomes of pediatric clinical myocarditis in China. We provided an extensive analysis of the clinical characteristics, diagnosis, treatment, prognosis, and factors impacting disease severity in pediatric clinical myocarditis in China, which provides insights into the epidemiological characteristics of pediatric clinical myocarditis.
Asunto(s)
Miocarditis , Niño , Humanos , Miocarditis/diagnóstico , Miocarditis/terapia , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular Izquierda , Forma MB de la Creatina-Quinasa , Arritmias Cardíacas , China/epidemiologíaRESUMEN
AIM: To elaborate the underlying mechanisms by which IL-1ß promote progression of Dry eye disease(DED) through effect on pyroptosis and apoptosis of corneal epithelial cells(CECs). METHODS: 400 mOsM solutions were used to establish the DED model (hCECs- DED). RT-qPCR was performed to measure IL-1ß mRNA and miR-146a-5p in CECs. Western blotting was performed to measure STAT3, GSDMD, NLRP3, and Caspase-1 levels. Cell counting kit-8 assay was adopted to check cell viability. Apoptosis was detected by flow cytometry. ELISAs were performed to determine IL-18, IL-33 and LDH. The luciferase test detects targeting relationships. RESULTS: After treatment with 400 mOsM solution, cell viability decreased and apoptosis increased. Compared with hCECs, IL-1ß was increased and miR-146a-5p was decreased in hCECs-DED. At the same time, GSDMD, NLRP3, Caspase-1, IL-18, IL-33 and LDH were significantly higher in hCECs-DED than in hCECs, while IL-1ß silencing reversed this effect. In addition, IL-1ß negatively regulated miR-146a-5p. MiR-146a-5p mimics eliminated the inhibition of hCECs-DED pyroptosis and apoptosis caused by IL-1ß silencing. At the same time, miR-146a-5p reduced STAT3 levels in hCECs. CONCLUSION: Highly expressed IL-1ß promoted pyroptosis and apoptosis of hCECs- DED through downregulated miR-146a-5p and inhibited STAT3.
Asunto(s)
Síndromes de Ojo Seco , MicroARNs , Humanos , Piroptosis , MicroARNs/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Interleucina-33/genética , Regulación hacia Abajo , Apoptosis , Síndromes de Ojo Seco/genética , Células Epiteliales/metabolismo , Caspasas/genética , Factor de Transcripción STAT3/genéticaRESUMEN
Entomopathogenic nematodes (EPNs) use the chemical cues emitted by insects and insect-damaged plants to locate their hosts. Steinernema carpocapsae, a species of EPN, is an established biocontrol agent used against insect pests. Despite its promising potential, the molecular mechanisms underlying its ability to detect plant volatiles remain poorly understood. In this study, we investigated the response of S. carpocapsae infective juveniles (IJs) to 8 different plant volatiles. Among these, carvone was found to be the most attractive volatile compound. To understand the molecular basis of the response of IJs to carvone, we used RNA-Seq technology to identify gene expression changes in response to carvone treatment. Transcriptome analysis revealed 721 differentially expressed genes (DEGs) between carvone-treated and control groups, with 403 genes being significantly upregulated and 318 genes downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the responsive DEGs to carvone attraction were mainly involved in locomotion, localization, behavior, response to stimulus, and olfactory transduction. We also identified four upregulated genes of chemoreceptor and response to stimulus that were involved in the response of IJs to carvone attraction. Our results provide insights into the potential transcriptional mechanisms underlying the response of S. carpocapsae to carvone, which can be utilized to develop environmentally friendly strategies for attracting EPNs.
Asunto(s)
Monoterpenos Ciclohexánicos , Insectos , Rabdítidos , Animales , Rabdítidos/fisiologíaRESUMEN
PURPOSE: To enhance the understanding of histological healing after repairing medial meniscal posterior root tear (MMPRT) at an early stage, utilizing a goat model. METHODS: Eighteen adult goats, totaling thirty-six knee joints, were allocated into three groups (n = 12): Sham group (Sham), Root Tear group (RT), and Root Tear with Transosseous Suture group (RTS). At 12- and 24-week intervals post-surgery, all the knees were harvested for imaging, macroscopic, histological, and biomechanical assessments. RESULTS: The intact root served as a meniscus-bone interface which connected the tibial and the circular fibers of the meniscus, with a bony insertion and a root-meniscus transition. A direct-fibrous-connection displayed at the bony insertion proximal to the synovium in the RTS group, while the remaining regions of the root displayed indirect-fibrous healing. The healing in the RT group was disjointed and reminiscent of scar tissue. The RTS group exhibited a more pronounced coronal extrusion compared to the Sham group (0.42 ± 0.09 vs. 0.19 ± 0.02, P = 0.0012) but was improved relative to that of the RT group (0.49 ± 0.02, P = 0.0028). The failure load and stiffness of the RTS group were notably higher than those of the RT group, with a strength of 42.67% and a stiffness of 83.75% of the intact root. All the samples ruptured at the root-meniscus transitions. CONCLUSION: The incomplete healing may be attributed to the histological factors underlying the low healing rate and persistent MME. Notably, the region attached to the posterior-cruciate-ligament exhibited superior healing compared to other regions of the bony insertion in the repaired group. Conversely, the root-meniscus transition displayed discontinuity, representing a mechanical weakness in the healing process. CLINICAL RELEVANCE: Modifications of bone tunnel positioning and suture placement could be undertaken in subsequent studies to particularly enhance the healing of the root-meniscus transition.
RESUMEN
Strontium isotope(~(87)S/~(86)Sr) tracing technology has been widely used in animal remains and origin of modern food origin sources. However, due to the problems of sample contamination and cleaning, this technology has been applied less frequently in the tracing of plant remains. The Palace Museum preserves more than 1 000 relics of medicinal materials from the Forbidden City of the Qing Dynasty, which are rare precious materials for the study of Dao-di herbs. The well-preserved environment of these medicinal materials in the Forbidden City of the Qing Dynasty helps avoid external strontium contamination, making it possible to introduce strontium isotope technology in their tracing research. On this basis, this study discussed the principle of strontium isotope tracing technology and summarized the current research progress on tracing plant remains using strontium isotope. In addition, this study discussed three key problems and their respective solutions encountered when applying strontium isotope technology to the tracing research on medicinal materials from the Forbidden City of the Qing Dynasty: creating strontium isotope ratio maps, dealing with the wide range of traceable results, and addressing the sample contamination and cleaning challenges. The literature and historical materials of the Qing Dynasty are the important basis for understanding the distribution and application of Dao-di herbs in the Qing Dynasty. Based on literature research, the use of strontium isotope to trace the producing area of medicinal materials in the Forbidden City of the Qing Dynasty can provide physical evidence for relevant research. The combined evidence of historical materials and medicinal relics is expected to provide a new perspective for the study of Dao-di herbs in the Qing Dynasty and also provide a reference for the study of the revolution of Dao-di herbs producing areas.
Asunto(s)
Medicamentos Herbarios Chinos , Plantas Medicinales , Medicina Tradicional China , Tecnología , Isótopos de Estroncio , ChinaRESUMEN
There are abundant local chronicles in the Qing Dynasty, which provide rich literature for the research on the production of medicinal materials. This paper collates the contents of Fuling in the local chronicles of the Qing Dynasty to reveal the distribution of Fuling in China at that time. The distribution of Fuling in the local chronicles of the Qing Dynasty involved 318 county-level regions in 23 provinces. The distribution records were mainly found in Yunnan, Anhui, Hunan, Zhejiang, Fujian, Jiangxi, Shaanxi, and Hubei. The local chronicles of the Qing Dynasty showed that Yunnan was the Dao-di producing area of Fuling, which was consistent with the materia medica of the Ming and Qing Dynasties. In the Qing Dynasty, the quality of Fuling in Dabie Mountains of Anhui was excellent, and it was called "Anling". The development of Anling benefited from the introduction of planting technology from Yunnan and the development of characteristic cultivation technology, with the formation of a complete industrial chain covering planting, processing, and sales. The abundant historical materials of Fuling in the local chronicles of the Qing Dynasty provide not only a documentary basis for revealing the changes of the Dao-di producing areas but also a historical context for the development of modern Fuling-producing areas such as Fujian, Jiangxi, and Hunan. In addition to the information of producing areas, the local records recorded the quality, commodity evaluation, and cultivation techniques of Fuling, filling the gaps in ancient materia medica books and providing detailed historical materials for understanding the producing areas and application of Fuling in the Qing Dynasty.
Asunto(s)
Medicina Tradicional China , China , Medicina Tradicional China/historia , Humanos , Historia del Siglo XIX , Historia del Siglo XVII , Medicamentos Herbarios Chinos/historia , Medicamentos Herbarios Chinos/química , Historia Antigua , Historia del Siglo XVIIIRESUMEN
This study aims to reveal the differences in the species and relative content of metabolites in the leaf and root tuber of Fallopia multiflora and improve the comprehensive utilization rate of F. multiflora resources. The metabolites in the root tubers and leaves of F. multiflora were detected by widely targeted metabolomics based on ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS). The principal component analysis, hierarchical cluster analysis, and orthogonal partial least squares-discriminant analysis were carried out to screen the differential metabolites between the leaf and root tuber of F. multiflora. The result showed that a total of 1 942 metabolites in 15 categories were detected in the leaf and root tuber of F. multiflora, including 1 861 metabolites in the root tuber, 1 901 metabolites in the leaf, and 1 820 metabolites in both. The metabolites were mainly phenolic acids, flavonoids, amino acids and derivatives, and alkaloids. A total of 1 200 differential metabolites were screened out, accounting for 65.9% of the total metabolites. Among these differential metabolites, 813 and 387 showed higher content in the leaf and root tuber, respectively. Flavonoids were the metabolites with the largest number and the most significant differences between the leaf and root tuber, and stilbenes and anthraquinones as the main active compounds mainly existed in the root tuber. The KEGG enrichment results suggested that the differential metabolites were mainly enriched in flavonoid and flavonol biosynthesis pathways and linoleic acid metabolism pathway. This study discovered abundant metabolites in F. multiflora. The metabolites were similar but had great differences in the content between the leaf and root tuber. The research results provide theoretical guidance for the development and utilization of F. multiflora resources.
Asunto(s)
Fallopia multiflora , Metabolómica , Hojas de la Planta , Raíces de Plantas , Hojas de la Planta/metabolismo , Hojas de la Planta/química , Raíces de Plantas/metabolismo , Raíces de Plantas/química , Cromatografía Líquida de Alta Presión , Fallopia multiflora/química , Fallopia multiflora/metabolismo , Tubérculos de la Planta/metabolismo , Tubérculos de la Planta/química , Espectrometría de Masas en Tándem , Flavonoides/metabolismo , Flavonoides/análisisRESUMEN
Flavonoid C-glycosides are a class of natural products that are widely involved in plant defense responses and have diverse pharmacological activities. They are also important active ingredients of Dendrobium huoshanense. Flavanone synthase â ¡ has been proven to be a key enzyme in the synthesis pathway of flavonoid C-glycosides in plants, and their catalytic product 2-hydroxyflavanone is the precursor compound for the synthesis of various reported flavonoid C-glycosides. In this study, based on the reported amino acid sequence of flavanone synthase â ¡, a flavanone synthase â ¡ gene(DhuFNSâ ¡) was screened and verified from the constructed D. huoshanense genome localization database. Functional validation of the enzyme showed that it could in vitro catalyze naringenin and pinocembrin to produce apigenin and chrysin, respectively. The open reading frame(ORF) of DhuFNSâ ¡ was 1 644 bp in length, encoding 547 amino acids. Subcellular localization showed that the protein was localized on the endoplasmic reticulum. RT-qPCR results showed that DhuFNSâ ¡ had the highest expression in stems, followed by leaves and roots. The expression levels of DhuFNSâ ¡ and other target genes in various tissues of D. huoshanense were significantly up-regulated after four kinds of abiotic stresses commonly encountered in the growth process, but the extent of up-regulation varied among treatment groups, with drought and cold stress having more significant effects on gene expression levels. Through the identification and functional analysis of DhuFNSâ ¡, this study is expected to contribute to the elucidation of the molecular mechanism of the formation of quality metabolites of D. huoshanense, flavonoid C-glycosides, and provide a reference for its quality formation and scientific cultivation.
Asunto(s)
Dendrobium , Flavanonas , Dendrobium/genética , Dendrobium/química , Flavanonas/metabolismo , Flavonoides , Clonación Molecular , Glicósidos/metabolismoRESUMEN
OBJECTIVE: The purpose of this study is to develop an anti-PDL1-based interferon (IFN) fusion protein to overcome the chronic hepatitis B virus (HBV)-induced immune tolerance, and combine this immunotherapy with a HBV vaccine to achieve the functional cure of chronic hepatitis B (CHB) infection. DESIGN: We designed an anti-PDL1-IFNα heterodimeric fusion protein, in which one arm was derived from anti-PDL1 antibody and the other arm was IFNα, to allow targeted delivery of IFNα into the liver by anti-PDL1 antibody. The effect of the anti-PDL1-IFNα heterodimer on overcoming hepatitis B surface antigen (HBsAg) vaccine resistance was evaluated in chronic HBV carrier mice. RESULTS: The anti-PDL1-IFNα heterodimer preferentially targeted the liver and resulted in viral suppression, the PD1/PDL1 immune checkpoint blockade and dendritic cell activation/antigen presentation to activate HBsAg-specific T cells, thus breaking immune tolerance in chronic HBV carrier mice. When an HBsAg vaccine was administered soon after anti-PDL1-IFNα heterodimer treatment, we observed strong anti-HBsAg antibody and HBsAg-specific T cell responses for efficient HBsAg clearance in chronic HBV carrier mice that received the combination treatment but not in those that received either single treatment. CONCLUSIONS: Targeting the liver with an engineered anti-PDL1-IFNα heterodimer can break HBV-induced immune tolerance to an HBsAg vaccine, offering a promising translatable therapeutic strategy for the functional cure of CHB.
Asunto(s)
Virus de la Hepatitis B , Hepatitis B Crónica , Ratones , Animales , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Antígenos de Superficie de la Hepatitis B , Vacunas contra Hepatitis B , Interferón-alfa/uso terapéutico , Tolerancia InmunológicaRESUMEN
Brugada syndrome is an inherited cardiac arrythmia causes sudden death usually associated with loss-of-function mutations of SCN5A, a gene encodes α subunit of cardiac sodium channel Nav1.5 which plays key role in cardiac function. SCN5A mutation screen is often applied to diagnosis of Brugada syndrome, while its genetic etiology remains not fully understood. In present study, we performed sequence analysis of SCN5A gene in a Chinese Han family with Brugada syndrome, and found a novel heterozygous mutation (c.4969 C > T, p.Leu1657Phe). Functional electrophysiological study showed that the mutation reduced â¼60% sodium current density and largely reduced Nav1.5 activation (positively shifted activation curve by 13.93 mV), which are the key features for the pathogenesis of Brugada syndrome. However, the mutation enhanced Nav1.5 function as it slightly decreased inactivation (positively shifted inactivation curve by 7.4 mV) and accelerated recovery (decreased fast recovery by 1.39 ms). In addition, the mutation acts in a dominant negatively manner as it reduced â¼49% sodium current densities in heterozygous state. In conclusion, the study describes a novel SCN5A mutation of p.Leu1657Phe associated with Brugada syndrome, the mutation reduced current density in a dominant negative manner and altered gating kinetics, which will benefit early clinical diagnosis of Brugada syndrome.
Asunto(s)
Síndrome de Brugada , Canal de Sodio Activado por Voltaje NAV1.5 , Humanos , Síndrome de Brugada/genética , Pueblos del Este de Asia , Mutación , Mutación Missense , Canal de Sodio Activado por Voltaje NAV1.5/genética , Sodio/metabolismoRESUMEN
Gene tree discordance is a significant legacy of biological evolution. Multiple factors can result in incongruence among genes, such as introgression, incomplete lineage sorting (ILS), gene duplication or loss. Resolving the background of gene tree discordance is a critical way to uncover the process of species diversification. Camellia, the largest genus in Theaceae, has controversial taxonomy and systematics due in part to a complex evolutionary history. We used 60 transcriptomes of 55 species, which represented 15 sections of Camellia to investigate its phylogeny and the possible causes of gene tree discordance. We conducted gene tree discordance analysis based on 1,617 orthologous low-copy nuclear genes, primarily using coalescent species trees and polytomy tests to distinguish hard and soft conflict. A selective pressure analysis was also performed to assess the impact of selection on phylogenetic topology reconstruction. Our results detected different levels of gene tree discordance in the backbone of Camellia, and recovered rapid diversification as one of the possible causes of gene tree discordance. Furthermore, we confirmed that none of the currently proposed sections of Camellia was monophyletic. Comparisons among datasets partitioned under different selective pressure regimes showed that integrating all orthologous genes provided the best phylogenetic resolution of the species tree of Camellia. The findings of this study reveal rapid diversification as a major source of gene tree discordance in Camellia and will facilitate future investigation of reticulate relationships at the species level in this important plant genus.
Asunto(s)
Camellia , Theaceae , Camellia/genética , Filogenia , Evolución Biológica , Duplicación de GenRESUMEN
Photosynthetic picoeukaryotes (PPEs) form associations with other microorganisms. However, whether and how the associated microbes affect PPE communities remain unknown. We used flow cytometric cell sorting combined with parallel high-throughput sequencing of the 18S and 16S rRNA genes to simultaneously investigate PPEs and their associated microbial communities in the Yangtze-connected Lake Dongting. The lake harbors a great diversity of PPEs. PPE communities exhibited significant temporal rather than spatial variations. Two distinct PPE taxa affiliated with Discostella nipponica and Poterioochromonas malhamensis were dominant during winter/spring and summer, respectively. Parallel high-throughput sequencing revealed a great diversity of associated bacteria and non-pigmented eukaryotes (NPEs) in PPEs sorts. Proteobacteria, Actinobacteria, Bacteroidetes, and Cyanobacteria among the associated bacteria and fungi among the associated NPEs were dominant. PPEs were more apparently associated with bacteria than with NPEs. The co-occurrence network of PPEs and associated microbes formed five major modules, which exhibited distinct temporal patterns, being specific to a certain period. Variations in PPEs communities were significantly correlated with both environmental factors and associated microbial communities. In variation partitioning analysis, the associated bacteria explained the greatest variations in PPE communities, and associated bacteria and NPEs co-explained a large portion of environmental effects on PPE communities. Our results highlight the significance of associated microbes in shaping PPE communities.
Asunto(s)
Chlorophyta , Diatomeas , Estramenopilos , ARN Ribosómico 16S/genética , Fotosíntesis , Estramenopilos/genética , Bacterias/genéticaRESUMEN
BACKGROUND: Lifestyle changes are important for the prevention and management of metabolic syndrome (MetS), but studies that focus on gender differences in the lifestyle risk factors of MetS are limited in China. This research aimed to generate a healthy lifestyle index (HLI) to assess the behavioral risk factors of MetS and its components, and to explore the gender differences in HLI score and other influencing factors of MetS. METHODS: A convenience sample of 532 outpatients were recruited from a general hospital in Changsha, China. The general information and HLI scores [including physical activity (PA), diet, smoking, alcohol use, and body mass index (BMI)] of the subjects were collected through questionnaires, and each patient's height, weight, waist circumference, and other physical signs were measured. Logistic regression analysis was used to analyze the risk factors of MetS and its components. RESULTS: The prevalence of MetS was 33.3% for the whole sample (46.3% in males and 23.3% in females). The risk of MetS increased with age, smoking, unhealthy diet, and BMI in males and with age and BMI in females. Our logistic regression analysis showed that lower HLI (male: OR = 0.838,95%CI = 0.757-0.929; female: OR = 0.752, 95%CI = 0.645-0.876) and older age (male: OR = 2.899, 95%CI = 1.446-5.812; female: OR = 4.430, 95%CI = 1.640-11.969) were independent risk factors of MetS, for both sexes. CONCLUSION: Low levels of HLI and older ages were independent risk factors of MetS in both males and females. The association between aging and MetS risk was stronger in females, while the association between unhealthy lifestyles and MetS risk was stronger in males. Our findings reinforced the expected gender differences in MetS prevalence and its risk factors, which has implications for the future development of gender-specific MetS prevention and intervention programs.
Asunto(s)
Síndrome Metabólico , Humanos , Masculino , Femenino , Síndrome Metabólico/epidemiología , Síndrome Metabólico/diagnóstico , Estudios Transversales , Factores Sexuales , Factores de Riesgo , Estilo de Vida Saludable , Índice de Masa Corporal , PrevalenciaRESUMEN
OBJECTIVE: Preterm infants with bronchopulmonary dysplasia (BPD) are at increased risk for dysfunctional immune responses in the postnatal period. This study aimed to verify the hypothesis that thymic function is altered in infants with BPD and changes in the expression of thymic function-related genes affect thymic development. STUDY DESIGN: Included in the study were infants who had a gestational age ≤32 weeks and survived to a postmenstrual age of ≥36 weeks. The clinical features and thymic size were comparatively studied between infants with and without BPD. Thymic function and the expression of thymic function-related genes were determined in BPD infants at birth, week 2, and 4 of life. The thymic size was ultrasonographically assessed in terms of the thymic index (TI) and thymic weight index (TWI). T-cell receptor excision circles (TRECs) and gene expression were quantitatively determined by real-time quantitative reverse transcription polymerase chain reaction. RESULTS: Compared to non-BPD infants, their BPD counterparts had a shorter GA, lower birth weight, lower Apgar scores at birth, and were more likely to be of the male gender. BPD infants had an elevated incidence of respiratory distress syndrome and sepsis. TI was 1.73 ± 0.68 versus 2.87 ± 0.70 cm3 and TWI was 1.38 ± 0.45 versus 1.72 ± 0.28 cm3/kg in the BPD group versus the non-BPD group (p < 0.05). In BPD infants, no significant changes were observed in thymic size, lymphocyte counts, and TREC copy numbers at the first 2 weeks (p > 0.05), but they all exhibited a significant increase at week 4 (p < 0.05). BPD infants presented a trend toward increased expression of transforming growth factor-ß1 and decreased expression of forkhead box protein 3 (Foxp3) from birth to week 4 (p < 0.05). Nonetheless, no significant difference was found in IL-2 or IL-7 expression at all time points (p > 0.05). CONCLUSION: For preterm infants with BPD, reduced thymic size at birth might be associated with impaired thymic function. Thymic function was developmentally regulated in the BPD process. KEY POINTS: · For preterm infants with BPD, reduced thymic size at birth might be associated with impaired thymic.. · BPD infants had an elevated incidence of respiratory distress syndrome and sepsis.. · Thymic function was developmentally regulated in the BPD process..