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BACKGROUND: The growth and development of organism were dependent on the effect of genetic, environment, and their interaction. In recent decades, lots of candidate additive genetic markers and genes had been detected by using genome-widely association study (GWAS). However, restricted to computing power and practical tool, the interactive effect of markers and genes were not revealed clearly. And utilization of these interactive markers is difficult in the breeding and prediction, such as genome selection (GS). RESULTS: Through the Power-FDR curve, the GbyE algorithm can detect more significant genetic loci at different levels of genetic correlation and heritability, especially at low heritability levels. The additive effect of GbyE exhibits high significance on certain chromosomes, while the interactive effect detects more significant sites on other chromosomes, which were not detected in the first two parts. In prediction accuracy testing, in most cases of heritability and genetic correlation, the majority of prediction accuracy of GbyE is significantly higher than that of the mean method, regardless of whether the rrBLUP model or BGLR model is used for statistics. The GbyE algorithm improves the prediction accuracy of the three Bayesian models BRR, BayesA, and BayesLASSO using information from genetic by environmental interaction (G × E) and increases the prediction accuracy by 9.4%, 9.1%, and 11%, respectively, relative to the Mean value method. The GbyE algorithm is significantly superior to the mean method in the absence of a single environment, regardless of the combination of heritability and genetic correlation, especially in the case of high genetic correlation and heritability. CONCLUSIONS: Therefore, this study constructed a new genotype design model program (GbyE) for GWAS and GS using Kronecker product. which was able to clearly estimate the additive and interactive effects separately. The results showed that GbyE can provide higher statistical power for the GWAS and more prediction accuracy of the GS models. In addition, GbyE gives varying degrees of improvement of prediction accuracy in three Bayesian models (BRR, BayesA, and BayesCpi). Whatever the phenotype were missed in the single environment or multiple environments, the GbyE also makes better prediction for inference population set. This study helps us understand the interactive relationship between genomic and environment in the complex traits. The GbyE source code is available at the GitHub website ( https://github.com/liu-xinrui/GbyE ).
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Sitios de Carácter Cuantitativo , Selección Genética , Teorema de Bayes , Modelos Genéticos , Fenotipo , Genotipo , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: The yak is a symbol of the Qinghai-Tibet Plateau and provides important basic resources for human life on the plateau. Domestic yaks have been subjected to strong artificial selection and environmental pressures over the long-term. Understanding the molecular mechanisms of phenotypic differences in yak populations can reveal key functional genes involved in the domestication process and improve genetic breeding. MATERIAL AND METHOD: Here, we re-sequenced 80 yaks (Maiwa, Yushu, and Huanhu populations) to identify single-nucleotide polymorphisms (SNPs) as genetic variants. After filtering and quality control, remaining SNPs were kept to identify the genome-wide regions of selective sweeps associated with domestic traits. The four methods (π, XPEHH, iHS, and XP-nSL) were used to detect the population genetic separation. RESULTS: By comparing the differences in the population stratification, linkage disequilibrium decay rate, and characteristic selective sweep signals, we identified 203 putative selective regions of domestic traits, 45 of which were mapped to 27 known genes. They were clustered into 4 major GO biological process terms. All known genes were associated with seven major domestication traits, such as dwarfism (ANKRD28), milk (HECW1, HECW2, and OSBPL2), meat (SPATA5 and GRHL2), fertility (BTBD11 and ARFIP1), adaptation (NCKAP5, ANTXR1, LAMA5, OSBPL2, AOC2, and RYR2), growth (GRHL2, GRID2, SMARCAL1, and EPHB2), and the immune system (INPP5D and ADCYAP1R1). CONCLUSIONS: We provided there is an obvious genetic different among domestic progress in these three yak populations. Our findings improve the understanding of the major genetic switches and domestic processes among yak populations.
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ATPasas Asociadas con Actividades Celulares Diversas , Domesticación , Receptores de Esteroides , Animales , Humanos , Bovinos/genética , Genoma , Análisis de Secuencia de ADN , Tibet , Genética de Población , Proteínas de Microfilamentos , Receptores de Superficie Celular , ADN Helicasas , Proteínas del Tejido Nervioso , Ubiquitina-Proteína LigasasRESUMEN
Understanding dephasing mechanisms of strong-field-driven excitons in condensed matter is essential for their applications in quantum-state manipulation and ultrafast optical modulations. However, experimental access to exciton dephasing under strong-field conditions is challenging. In this study, using time- and spectrum-resolved quantum-path interferometry, we investigate the dephasing mechanisms of terahertz-driven excitonic Autler-Townes doublets in MoS_{2}. Our results reveal a dramatic increase in the dephasing rate beyond a threshold field strength, indicating exciton dissociation as the primary dephasing mechanism. Furthermore, we demonstrate nonperturbative high-order sideband generation in a regime where the driving fields are insufficient to dissociate excitons.
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The metal-support interaction is crucial for the performance of Cu-based catalysts. However, the distinctive properties of the support metal element itself are often overlooked in catalyst design. In this paper, a sheet Cu-Zn-Ce with [Ce3+-OV-Ce4+] located on the surface was designed by the sol-gel method. Through EPR and X-ray photoelectron spectroscopy (XPS), the relationship between the content of oxygen vacancies and Ce was revealed. Ce itself induces the generation of [Ce3+-OV-Ce4+]. Through ICP-MS, XPS, and SEM-mapping, the Ce-induced formation of [Ce3+-OV-Ce4+] located on the catalyst surface was demonstrated. CO2-TPD and DFT calculations further revealed that [Ce3+-OV-Ce4+] enhanced CO2 adsorption, leading to a 10% increase in methanol selectivity compared to Cu-Zn-Ce synthesized via the coprecipitation method.
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Organophosphate diesters (di-OPEs), as additives in industrial applications and/or transformation products of emerging environmental pollutants, such as organophosphate triesters (tri-OPEs), have been found in the environment and biological matrices. The metabolic fate of di-OPEs in biological media is of great significance for tracing the inherent and precursor toxicity variations. This is the first study to investigate the metabolism of a suite of di-OPEs by liver microsomes and to identify any metabolite of metabolizable di-OPEs in in vitro and in vivo samples. Of the 14 di-OPEs, 5 are significantly metabolizable, and their abundant metabolites with hydroxyl, carboxyl, dealkylated, carbonyl, and/or epoxide groups are tentatively identified. More than half of the di-OPEs are detectable in human serum and/or wild fish tissues, and dibenzyl phosphate (DBzP), bis(2,3-dibromopropyl) phosphate (BDBPP), and isopropyl diphenyl phosphate (ip-DPHP) are first reported at a detectable level in humans and wildlife. Using an in vitro assay and a known biotransformation rule-based integrated screening strategy, 2 and 10 suspected metabolite peaks of DEHP are found in human serum and wild fish samples, respectively, and are then identified as phase I and phase II metabolites of DEHP. This study provides a novel insight into fate and persistence of di-OPE and confirms the presence of di-OPE metabolites in humans and wildlife.
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Dietilhexil Ftalato , Retardadores de Llama , Animales , Humanos , Organofosfatos , Retardadores de Llama/análisis , Ésteres , Biotransformación , Fosfatos , China , Monitoreo del AmbienteRESUMEN
Benzo[a]pyrene is difficult to remove from soil due to its high octanol/water partition coefficient. The use of mixed surfactants can increase solubility but with the risk of secondary soil contamination, and the compounding mechanism is still unclear. This study introduced a new approach using environmentally friendly fatty acid methyl ester sulfonate (MES) and alkyl polyglucoside (APG) to solubilize benzo[a]pyrene. The best result was obtained when the ratio of MES/APG was 7:1 under 6 g/L total concentration, with an apparent solubility (Sw) of 8.58 mg/L and a molar solubilization ratio (MSR) of 1.31 for benzo[a]pyrene, which is comparable to that of Tween 80 (MSR, 0.95). The mechanism indicates that the hydroxyl groups (-OH) in APG form "O-H···OSO2-" hydrogen bonding with the sulfonic acid group (-SO3-) of MES, which reduces the electrostatic repulsion between MES molecules, thus facilitating the formation of large and stable micelles. Moreover, the strong solubilizing effect on benzo[a]pyrene should be ascribed to the low polarity of ester groups (-COOCH3) in MES. Functional groups capable of forming hydrogen bonds and having low polarity are responsible for the enhanced solubilization of benzo[a]pyrene. This understanding helps choose suitable surfactants for the remediation of PAH-contaminated soils.
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Benzo(a)pireno , Solubilidad , Tensoactivos , Tensoactivos/química , Benzo(a)pireno/química , Contaminantes del Suelo/químicaRESUMEN
The innovative synthesis of 3,8-dibromo-2,9-dinitro-5,6-dihydrodiimidazo [1,2-a:2',1'-c]pyrazine and 3,9-dibromo-2,10-dinitro-6,7-dihydro-5H-diimidazo [1,2-a:2',1'-c][1,4]diazepine is described in this study. The tricyclic fused molecular structures are formed by the respective amalgamation of piperazine and homopiperazine with the imidazole ring containing nitro. Compound 1 and 2 possess excellent high-density physical properties (ρ1 = 2.49 g/cm3, ρ2 = 2.35 g/cm3) due to the presence of a fused ring structure and Br atom. In addition to their high density, they have high decomposition temperatures (Td > 290 °C) which means that they have excellent thermal stability and can be used as potential heat-resistant explosives. Low mechanical sensitivities (IS > 40 J, FS > 360 N) are observed. The twinning structure of 2 was resolved by X-ray diffraction. Non-covalent interaction analysis, Hirshfeld surfaces, 2D fingerprint plot, and Electrostatic potential analysis were used to understand the intramolecular interactions in relation to physicochemical properties. The unique structures of this type of compound provide new potential for the evolution of energetic materials.
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BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a serious chronic disease worldwide, with significant negative impacts on the quality of life, family economic burden, and social healthcare burden of patients. AIMS: The aim of this study was to explore the effects of virtual reality technology on exercise function and lung function in COPD patients. METHODS: A meta-analysis of randomized controlled trials was utilized. PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, Medline, Scopus, China National Knowledge Infrastructure (CNKI), Wanfang Database, Weipu Database (VIP), and Chinese Biomedical Database (CBM) were systematically searched. We included randomized controlled trials published from the establishment of the database to August 10, 2022, on virtual reality technology in COPD patients. Literature retrieval and screening was carried out independently by two reviewers to obtain literature that met our inclusion and exclusion criteria and to extract relevant data. Two reviewers assessed the risk of bias in the included literature. A meta-analysis was performed using Revman 5.4 Software. RESULTS: A total of 10 randomized controlled trials with 539 participants were included. The results showed that virtual reality technology significantly improved the lung function of COPD patients, such as forced expiratory volume (FEV1; MD = 7.29, 95% CI [4.34, 10.24], p < .01) and forced expiratory volume/forced vital capacity (FEV1/FVC; MD = 6.71, 95% CI [4.72, 8.71], p < .01). The combined intervention with different virtual reality technology had different effects on motor function. Compared with endurance training (ET) alone, virtual reality technology combined with ET had no significant effect on the 6-minute walk test (6WMT) in COPD patients (p > .05). Compared with pulmonary rehabilitation (PR) alone, virtual reality technology combined with PR was more effective in increasing 6WMT in COPD patients (MD = 30.80, 95% CI [10.85, 50.74], p < .01). LINKING EVIDENCE TO ACTION: Virtual reality technology can help to improve lung function in COPD patients, and virtual reality combined with PR can improve exercise tolerance in COPD patients. However, due to the limited number of included studies, large-sample, multicenter, high-quality randomized controlled trial studies are needed to provide clear evidence.
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Enfermedad Pulmonar Obstructiva Crónica , Realidad Virtual , Humanos , Enfermedad Pulmonar Obstructiva Crónica/psicología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria/métodos , Ejercicio Físico/fisiología , Ejercicio Físico/psicología , Calidad de Vida/psicologíaRESUMEN
BACKGROUND: Restless legs syndrome is associated with quality of life and risk of death in maintenance hemodialysis patients. Although relevant meta-analyses have been conducted, epidemiological studies of restless legs syndrome have increased in recent years. OBJECTIVE: Our aim was to systematically assess the prevalence of restless legs syndrome in maintenance hemodialysis patients and to evaluate the effect of different geographic regions, genders, study designs, and years of publication on the prevalence of restless legs syndrome. METHODS: PubMed, Web of Science, EMBASE, The Cochrane Library, China Knowledge Resource Integrated Database, Wanfang Database, Weipu, and Chinese Biomedical Database were searched before March 16, 2023 for the published literature. Two investigators independently performed literature screening, data extraction for eligible studies, and risk of bias assessment. A random-effects model using the stata 15.0 software was used to assess the pooled prevalence of restless legs syndrome. RESULTS: Fifty-seven articles were included in this meta-analysis, and the pooled prevalence of restless legs syndrome in 12,573 maintenance hemodialysis patients was 24.0 % (95 % CI: 21.0%-26.0 %). Maintenance hemodialysis patients from the Americas region and females had severe symptoms of restless legs syndrome, and the prevalence of restless legs syndrome increased from year to year. The prevalence of restless legs syndrome was higher in maintenance hemodialysis patients in cross-sectional studies and cohort studies compared to case-control studies. CONCLUSIONS: Maintenance hemodialysis patients have a significantly higher prevalence of restless legs syndrome. These findings may provide some reference value for hospital nursing staff to focus on the management and treatment of restless legs syndrome in maintenance hemodialysis patients.
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Diálisis Renal , Síndrome de las Piernas Inquietas , Síndrome de las Piernas Inquietas/epidemiología , Humanos , Diálisis Renal/efectos adversos , Prevalencia , FemeninoRESUMEN
This paper was concerned with a free boundary problem modeling the growth of tumor cord with a time delay in cell proliferation, in which the cell location was incorporated, the domain was bounded in $ \mathbb{R}^2 $, and its boundary included two disjoint closed curves, one fixed and the other moving and a priori unknown. A parameter $ \mu $ represents the aggressiveness of the tumor. We proved that there exists a unique radially symmetric stationary solution for sufficiently small time delay, and this stationary solution is linearly stable under the nonradially symmetric perturbations for any $ \mu > 0 $. Moreover, adding the time delay in the model leads to a larger stationary tumor. If the tumor aggressiveness parameter is bigger, the time delay has a greater effect on the size of the stationary tumor, but it has no effect on the stability of the stationary solution.
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Modelos Biológicos , Neoplasias , Humanos , Neoplasias/patología , Proliferación CelularRESUMEN
PURPOSE OF REVIEW: The 'PrEP cliff' phenomenon poses a critical challenge in global HIV PrEP implementation, marked by significant dropouts across the entire PrEP care continuum. This article reviews new strategies to address 'PrEP cliff'. RECENT FINDINGS: Canadian clinicians have developed a service delivery model that offers presumptive PEP to patients in need and transits eligible PEP users to PrEP. Early findings are promising. This service model not only establishes a safety net for those who were not protected by PrEP, but it also leverages the immediate salience and perceived benefits of PEP as a natural nudge towards PrEP use. Aligning with Behavioral Economics, specifically the Salience Theory, this strategy holds potential in tackling PrEP implementation challenges. SUMMARY: A natural pathway between PEP and PrEP has been widely observed. The Canadian service model exemplifies an innovative strategy that leverages this organic pathway and enhances the utility of both PEP and PrEP services. We offer theoretical insights into the reasons behind these PEP-PrEP transitions and evolve the Canadian model into a cohesive framework for implementation.
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Fármacos Anti-VIH , Economía del Comportamiento , Infecciones por VIH , Profilaxis Pre-Exposición , Humanos , Infecciones por VIH/prevención & control , Profilaxis Pre-Exposición/métodos , Profilaxis Pre-Exposición/economía , Canadá , Fármacos Anti-VIH/economía , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Profilaxis Posexposición/métodos , Profilaxis Posexposición/economíaRESUMEN
How do humans judge physical stability? A prevalent account emphasizes the mental simulation of physical events implemented by an intuitive physics engine in the mind. Here we test the extent to which the perceptual features of object geometry are sufficient for supporting judgments of falling direction. In all experiments, adults and children judged the falling direction of a tilted object and, across experiments, objects differed in the geometric features (i.e., geometric centroid, object height, base size and/or aspect ratio) relevant to the judgment. Participants' performance was compared to computational models trained on geometric features, as well as a deep convolutional neural network (ResNet-50), none of which incorporated mental simulation. Adult and child participants' performance was well fit by models of object geometry, particularly the geometric centroid. ResNet-50 also provided a good account of human performance. Altogether, our findings suggest that object geometry may be sufficient for judging the falling direction of tilted objects, independent of mental simulation.
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Intuición , Juicio , Adulto , Niño , Humanos , FísicaRESUMEN
INTRODUCTION: Mucinous cystadenocarcinoma (MCA) of the breast is an extremely rare type of breast carcinoma. Since its biological characteristics, treatment options, and clinical outcomes are unclear, there is a lack of consensus regarding the optimal management of this disease. Thus, our single case report will aid our understanding of its natural history, prognostic factors, and treatment strategies. CASE PRESENTATION: We presented a 54-year-old woman with a case of advanced MCA of the breast accompanied by a huge breast mass, lymph node involvement, and distant bone metastases. We diagnosed primary breast MCA through clinical examination, imaging, and immunohistochemical assessments. Subsequently, the patient was treated with a regimen of nab-paclitaxel and bevacizumab, resulting in a significant clinical response. Progression-free survival was maintained during the 6-month follow-up period. CONCLUSION: We present the first report worldwide of a rare case of MCA of the breast with a large local mass and bone metastases. Our report adds to the limited literature on this rare breast cancer subtype and highlights the importance of accurate diagnosis and appropriate management of aggressive breast tumors.
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Neoplasias de la Mama , Cistadenocarcinoma Mucinoso , Femenino , Humanos , Persona de Mediana Edad , Cistadenocarcinoma Mucinoso/diagnóstico , Cistadenocarcinoma Mucinoso/patología , Mama/patología , Neoplasias de la Mama/patología , Bevacizumab/uso terapéutico , Ganglios Linfáticos/patologíaRESUMEN
OBJECTIVES: This study aimed to determine the potential profiles of self-psychological adjustment in patients with lung cancer undergoing chemotherapy, including sense of coherence (SOC) and positive cognitive emotion regulation (PCER). The relationship between these profiles with post-traumatic growth (PTG) and the relevant factors of self-psychological adjustment in different profiles was analysed. DESIGN: Cross-sectional study. SETTING: Patients with lung cancer undergoing chemotherapy in China. PARTICIPANTS: A total of 330 patients with lung cancer undergoing chemotherapy were recruited out of which 321 completed the questionnaires effectively. METHODS: Latent profile analysis was used to identify self-psychological adjustment classes based on the two subscales of the Sense of Coherence Scale and Cognitive Emotion Regulation Questionnaire. One-way analysis of variance and multinomial logistic regression were performed to examine the subgroup association with characteristics and PTG. RESULTS: Three latent profiles of self-psychological adjustment were identified: low level (54.5%), high SOC-low PCER (15.6%) and high PCER (29.9%). The results of univariate analysis showed a significant difference in PTG scores among different self-psychological adjustment subgroups (F=11.55, p<0.001). Patients in the high-PCER group were more likely living in urban areas (OR=2.41, 95% CI 1.17 to 4.97, p=0.02), and time since cancer diagnosis was ≥6 months and <1 year (OR=3.54, 95% CI 1.3 to 9.64, p<0.001). CONCLUSION: This study revealed that most patients with lung cancer undergoing chemotherapy belonged to the low-level group. Three profiles are associated with PTG. There were differences in characteristics between patients treated with chemotherapy for lung cancer in the high-PCER and low-PCER groups. Thus, these profiles provide useful information for developing targeted individualised interventions based on demographic characteristics that would assist PTG in patients with lung cancer undergoing chemotherapy.
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Neoplasias Pulmonares , Crecimiento Psicológico Postraumático , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/psicología , Masculino , Estudios Transversales , Femenino , Persona de Mediana Edad , China/epidemiología , Anciano , Adaptación Psicológica , Sentido de Coherencia , Encuestas y Cuestionarios , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Adulto , Ajuste EmocionalRESUMEN
Nickel-catalyzed aqueous cyanation of allylic alcohols is herein described. This catalytic protocol provided environmentally friendly and operationally simple access to a variety of allylic nitriles in good yields. For chiral allylic alcohols, the reaction gave chiral allylic nitriles with a high degree of chiral inversion. The accelerated release of cyanide in H2O was crucial for the success of this reaction.
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BACKGROUND AND AIMS: Idiopathic restrictive cardiomyopathy (RCM) has a low incidence. This study aimed to determine the prognostic value of big endothelin-1 (ET-1) in idiopathic RCM. MATERIALS AND METHODS: We prospectively enrolled patients with idiopathic RCM from 2009 to 2017 and followed them up. The primary outcome was a composite of all-cause mortality and cardiac transplantation, and the secondary outcome was a composite of cardiac death and cardiac transplantation. RESULTS: Ninety-one patients were divided into the high big ET-1 (>0.85 pmol/L, n = 56) and low big ET-1 (≤0.85 pmol/L, n = 35) groups, and 87 of them completed the follow-up. Big ET-1 concentrations (hazard ratio: 1.756, 95 % confidence interval [CI]: 1.117-2.760) and late gadolinium enhancement (LGE) (hazard ratio: 3.851, 95 % CI: 1.238-11.981) were independent risk factors for the primary outcome. Big ET-1 concentrations (C-statistic estimation: 0.764, 95 % CI: 0.657-0.871) and the combination of LGE and big ET-1 concentrations (C-statistic estimation: 0.870, 95 % CI: 0.769-0.970) could accurately predict the 5-year transplant-free survival rate, and 0.85 pmol/L was a suitable cutoff for big ET-1. CONCLUSION: Big ET-1 and its combination with LGE may be useful to predict an adverse prognosis in patients with idiopathic RCM.
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Cardiomiopatía Restrictiva , Endotelina-1 , Gadolinio , Humanos , Endotelina-1/sangre , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Cardiomiopatía Restrictiva/diagnóstico , Cardiomiopatía Restrictiva/diagnóstico por imagen , Adulto , Estudios Prospectivos , Imagen por Resonancia Magnética , Medios de ContrasteRESUMEN
Sarcoplasmic calcium-binding protein (Cra a 4) from Crassostrea angulata belongs to the EF-hand superfamily, and understanding of its structure-allergenicity relationship is still insufficient. In this study, chemical denaturants were used to destroy the structure of Cra a 4, showing that disruption of the structure reduced its IgG-/IgE-binding activity. To explore which critical amino acid site affects the allergenicity of Cra a 4, the mutants were obtained by site-directed mutations in the disulfide bonds site (C97), conformational epitopes (I105, D114), or Ca2+-binding region (D106, D110) and their IgG-/IgE-binding activity was reduced significantly using serological tests. Notably, C97A had the lowest immunoreactivity. In addition, two conformational epitopes of Cra 4 were verified. Meanwhile, the increase of the α-helical content, surface hydrophobicity, and surface electrostatic potential of C97A affected its allergenicity. Overall, the understanding of the structure-allergenicity relationship of Cra a 4 allowed the development of a hypoallergenic mutant.
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Liddle syndrome is an autosomal dominant form of monogenic hypertension that is caused by mutations in SCNN1A, SCNN1B or SCNN1G, which respectively encode the α, ß and γ subunits of the epithelial sodium channel. In the present study, DNA was extracted from leukocytes in peripheral blood obtained from all members of a family with Liddle syndrome. Wholeexome sequencing and Sanger sequencing were performed to assess the candidate variant and a cosegregation analysis was conducted. A frameshift mutation in SCNN1B (NM_ 000336: c.1806dupG, p.Pro603Alafs*5) in the family was identified, characterized by earlyonset hypertension and hypokalemia. The mutation led to the truncation of the ß subunit of the epithelial sodium channel and a lack of the conservative PY motif. Furthermore, a systematic review of followup data from patients with Liddle syndrome with SCNN1B mutations was performed. The followup data of 108 patients with pathogenic SCNN1B mutations from 47 families were summarized. Phenotypic heterogeneity was evident in patients with Liddle syndrome and earlyonset hypertension was the most frequent symptom. Patients responded well to targeted amiloride therapy with significant improvements in blood pressure and serum potassium concentration. The present study demonstrates that confirmatory genetic testing and targeted therapy can prevent premature onset of clinical endpoint events in patients with Liddle syndrome.
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Hipertensión , Síndrome de Liddle , Humanos , Síndrome de Liddle/diagnóstico , Síndrome de Liddle/genética , Síndrome de Liddle/tratamiento farmacológico , Canales Epiteliales de Sodio/genética , Mutación del Sistema de Lectura , Mutación , Hipertensión/genética , Hipertensión/tratamiento farmacológico , PotasioRESUMEN
Tripartite motif 21 (TRIM21) is a cytosolic Fc receptor that targets antibody-bound, internalized pathogens for destruction. Apart from this intrinsic defense role, TRIM21 is implicated in autoimmune diseases, inflammation, and autophagy. Whether TRIM21 participates in host interactions with influenza A virus (IAV), however, is unknown. By computational modeling of body weight and lung transcriptome data from the BXD parents (C57BL/6 J (B6) and DBA/2 J (D2)) and 41 BXD mouse strains challenged by IAV, we reveal that a Trim21-associated gene network modulates the early host responses to IAV infection. Trim21 transcripts were significantly upregulated in infected mice of both B6 and D2 backgrounds. Its expression was significantly higher in infected D2 than in infected B6 early after infection and significantly correlated with body weight loss. We identified significant trans-eQTL on chromosome 14 that regulates Trim21 expression. Nr1d2 and Il3ra were among the strongest candidate genes. Pathway analysis found Trim21 to be involved in inflammation and immunity related pathways, such as inflammation signaling pathways (TNF, IL-17, and NF-κB), viral detection signaling pathways (NOD-like and RIG-I-like), influenza, and other respiratory viral infections. Knockdown of TRIM21 in human lung epithelial A549 cells significantly augmented IAV-induced expression of IFNB1, IFNL1, CCL5, CXCL10, and IFN-stimulated genes including DDX58 and IFIH1, among others. Our data suggest that a TRIM21-associated gene network is involved in several aspects of inflammation and viral detection mechanisms during IAV infection. We identify and validate TRIM21 as a critical regulator of innate immune responses to IAV in human lung epithelial cells.
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Encefalitis de California , Inmunidad Innata , Animales , Humanos , Ratones , Proteína 58 DEAD Box , Inflamación , Pulmón , Ratones Endogámicos C57BL , Ratones Endogámicos DBARESUMEN
The ionosphere can be artificially modified by employing ground-based high-power high-frequency electromagnetic waves to irradiate the ionosphere. This modification is achieved through the nonlinear interaction between the electromagnetic waves and the ionospheric plasma, leading to changes in the physical properties and structure of the ionosphere. The degree of artificial modification of the ionosphere is closely related to the heating energy density of high-frequency pump waves. Due to the high density of neutral constituents in the lower ionosphere and the high frequency of electron-neutral collisions, the energy of heating pump waves will be absorbed and attenuated during the penetration of the low ionosphere, seriously affecting the heating effect. This paper proposes a method to reduce the absorption of ionospheric heating pump waves by releasing electron attachment chemicals into low ionosphere to form a large-scale electron density hole. A model for mitigating pump waves absorption based on SF6 release is established, and the absorption at different frequencies is quantitatively calculated. The propagation characteristics of high-frequency signals in ionospheric holes are studied using a three-dimensional ray tracing method, and the results demonstrate that the chemical release method not only reduces the absorption attenuation of heating pump waves but also forms spherical electron density holes, which exhibit a focusing effect on the heating beam and enhance the heating effect. The results are of great significance for understanding the nonlinear interaction between electromagnetic wave and ionospheric plasma and improving the ionospheric heating efficiency.