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1.
Sci Rep ; 11(1): 19689, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34608242

RESUMO

Subclinical hypothyroidism (SCH) has become a prevalent complication in pregnancy. Recent research links SCH to disturbed thyroid lipid profile; however, it is unclear how lipid metabolism disorders contribute to the pathogenesis of SCH during pregnancy. Thus, we used nontargeted lipidomics to identify and compare the lipids and metabolites expressed by pregnant women with SCH and healthy pregnant women. Multivariate analysis revealed 143 lipid molecules differentially expressed between the SCH group and the control group. Based on fold change, 30 differentially expressed lipid metabolites are potential biomarkers. KEGG pathway enrichment analysis showed that the differentially expressed metabolites participate in several pathways, including response to pathogenic Escherichia coli infection, regulation of lipolysis in adipocytes, metabolic pathways, glycerophospholipid metabolism, and fat digestion and absorption pathways. Correlation analyses revealed sphingomyelin (SM) and phosphatidylcholine (PC) positively correlate to tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-6 (IL-6), while phosphatidylglycerol (PG), and phosphatidylinositol (PI) negatively correlate with them. In addition, PG positively correlates to birth weight. Thus, the lipid profile of pregnant women with SCH is significantly different from that of healthy pregnant women. Lipid molecules associated with the differential lipid metabolism, such as SM, phosphatidylethanolamine (PE), and PI, should be further investigated for their roles in the pathogenesis of SCH in pregnancy, as they might be targets for reducing the incidence of adverse pregnancy outcomes.

2.
Chem Commun (Camb) ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618880

RESUMO

A small amount of the 3-(hexyldimethylammonio)propane-1-sulfonate zwitterionic side chain was integrated into a diketopyrrolopyrrole ambipolar polymer to modulate its field-effect carrier-transport characteristics. It was found that such a modification can strengthen the interchain interaction, promote crystallization, and thus improve the hole and electron mobilities by 3.9- and 8.2-fold, respectively.

3.
Insect Sci ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647692

RESUMO

Homocysteine (Hcy) is a sulfur-containing amino acid derived from the essential amino acid methionine (Met). Circulating levels of Hcy in animals can be increased by feeding on Met-enriched diets, which is generally considered harmful. Spiders are one of the largest groups of obligate carnivores and feed on animals high in protein and Met. We analyzed the Hcy metabolism pathways in 18 species of three taxa (Mammalia, Insecta, and Arachnida) and found that the betaine-dependent remethylation pathway (BRP) was present in all carnivorous arachnid species and mammals but absent in insects and red spider mites. We then studied the Hcy metabolism pathway in Pardosa pseudoannulata. In P. pseudoannulata, Hcy is metabolized through the transsulfuration pathway, BRP, and S-methylmethionine-dependent remethylation pathway. Because of a prior duplication event of the betaine homocysteine S-methyltransferase (BHMT) gene in the BRP, BHMTa and BHMTb are present in tandem in the genome of P. pseudoannulata. The high expression levels of BHMTa and its high abundance in detoxification tissues indicate that it plays an important role in the BRP; the ability of BHMTa and BHMTb to remethylate Hcy using betaine as substrate was similar. Compared with other Hcy metabolic enzyme genes, BHMT responded quickly to the application of Hcy or betaine. In sum, the BRP is important in Hcy metabolism in P. pseudoannulata and in other spider species. This article is protected by copyright. All rights reserved.

4.
Perfusion ; : 2676591211046868, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617832

RESUMO

Aluminium phosphide (ALP) and aluminium zinc phosphide (ZnP), the two main ingredients of fumigation drugs, are commonly used to kill insects or rodents in grain. When exposed to water, highly toxic phosphine gas is released and absorbed through the respiratory or digestive tract. Phosphine gas could non-selectively block cytochrome oxidase, inhibit electron transfer and suppress oxidative phosphorylation, leading to cellular hypoxia and organ dysfunction. The characteristic clinical manifestations are refractory shock and metabolic acidosis with high mortality. However, patients with ALP poisoning have a chance to be cured. Here, we report a case of oral ALP poisoning that was successfully treated by extracorporeal membrane oxygenation (ECMO) combined with continuous renal replacement therapy (CRRT) during frequent ventricular fibrillation and cardiac dysfunction.

5.
Dev Comp Immunol ; 127: 104267, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34626689

RESUMO

A Dicer2 gene from Scylla paramamosain, named SpDicer2, was cloned and characterized. The full length of SpDicer2 mRNA contains a 121 bp 5'untranslated region (UTR), an open reading frame (ORF) of 4518 bp and a 3' UTR of 850 bp. The SpDicer2 protein contains seven characteristic Dicer domains and showed 34%-65% identity and 54%-79% similarity to other Dicer protein domains, respectively. The mRNA of SpDicer2 was high expressed in hemocytes, intestine and gill and low expressed in the eyestalk and muscle. Moreover, expression of SpDicer2 was significantly responsive to challenges by mud crab reovirus (MCRV), Poly(I:C), LPS, Staphylococcus aureus and Vibrio parahaemolyticus. SpDicer2 was dispersedly presented in the cytoplasm except for a small amount in the nucleus. SpDicer2 could activate SpSTAT to translocate from the cytoplasm to the nucleus, and significantly increase the transcription activity of the wsv069 promoter, suggesting that SpDicer2 activated the JAK/STAT pathway. Furthermore, silencing of SpDicer2 in vivo increased the mortality of MCRV infected mud crab and the viral load in tissues and down-regulated the expression of multiple components of Toll, IMD and JAK-STAT pathways and almost all the examined immune effector genes. These results suggested that SpDicer2 could play an important role in defense against MCRV via activating the JAK/STAT signaling pathways in mud crab.

6.
J Med Primatol ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34664268

RESUMO

BACKGROUND: Golden snub-nosed monkey (Rhinopithecus roxellana) is an endangered primate species, whose molecular material for conservation purposes has not yet been maintained. Although small-molecule compounds (SMCs) have been reported to improve induced pluripotent stem cells (iPSCs), their efficiency in the interspecies-transferred nucleus is still unknown. METHODS: We thus used the fibroblasts from the golden snub-nosed monkey treated with SMC as donor cells, injected into the enucleated oocytes of goats, to test such efficiency. Gene expression profiles in the cell-constructed embryos with and without SMCs were compared by qPCR. RESULTS: The results show that cell morphology undergoes remarkable changes (volume is smaller than normal cells, and many black spots in the cytoplasm were found); pluripotent genes (Oct4, Sox2, and Nanog) significantly increased with SMC treatment. CONCLUSIONS: This study demonstrates that SMCs alter the properties of donor cells and promote the expression of pluripotent genes in hybrid embryos.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34501614

RESUMO

Although a large number of studies have indicated that self-control was an important predictive factor for adolescent internet addiction, the moderating and mediating mechanisms underlying this relationship remain unclear. To address this research gap, the present study, according to social learning theory and the organism-environment interaction theory, tested whether consideration of future consequences mediated the relation between self-control and adolescent internet addiction and whether deviant peer affiliation moderated the relationship between consideration of future consequences and internet addiction. Using longitudinal tracking (two-time points and the interval is 6 months). Three middle schools in Guangzhou were randomly selected. The participants were 1182 students ranging in age from 12 to 15 years (average age: 14.16, SD = 1.29) from three middle schools in Guangzhou (651 boys and 531 girls) in Guangdong Province. Results showed that consideration of future consequences mediated the relationship between self-control and internet addiction. Furthermore, the relationship between future consequence consideration and internet addiction was moderated by deviant peer affiliation. These findings highlighted the potential mediating role of consideration of future consequences in linking self-control to adolescent internet addiction. We also found high deviant peer affiliation weakens the protective effect of future consequence consideration on Internet addiction. This study may provide support for adolescent Internet addiction prevention and have some educational implications.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34478362

RESUMO

Conventional machine learning algorithms suffer the problem that the model trained on existing data fails to generalize well to the data sampled from other distributions. To tackle this issue, unsupervised domain adaptation (UDA) transfers the knowledge learned from a well-labeled source domain to a different but related target domain where labeled data is unavailable. In this paper, we consider a more practical yet challenging UDA setting where either the source domain data or the target domain data are unknown. Technically, we investigate UDA from a novel view --- adversarial attack --- and tackle the divergence-agnostic adaptive learning problem in a unified framework. Specifically, we first report the motivation of our approach by investigating the inherent relationship between UDA and adversarial attacks. Then we elaborately design adversarial examples to attack the training model and harness these adversarial examples. We argue that the generalization ability of the model would be significantly improved if it can defend against our attack, so as to improve the performance on the target domain. Theoretically, we analyze the generalization bound for our method based on domain adaptation theories. Extensive experimental results verify that our method is able to achieve a favorable performance compared with previous ones.

9.
J Adolesc Health ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34531096

RESUMO

PURPOSE: The purpose of the study is to assess associations between exposure to a multilevel, socio-ecological health program administered by local education agencies and changes in health behaviors among high school students. METHODS: This analysis used a multilevel difference-in-differences approach to compare student health experiences and outcomes between schools selected by local education agencies nationwide to implement the program (exposed schools) and schools that were not (unexposed schools). We measured repeated cross-sectional outcomes using the 2015 and 2017 Youth Risk Behaviors Surveys. The final analytic sample comprised 638 schools in total (N = 64,838 students), with 237 exposed schools (n = 30,336 students) and 401 unexposed schools (n = 34,502 students). RESULTS: Students in exposed schools demonstrated significant reduction in odds compared with those in unexposed schools in ever having sex (adjusted odds ratio [aOR] = .88, 95% confidence interval [CI]: .81-.96), having four or more lifetime sexual partners (aOR = .84, 95% CI: .72-.97), being currently sexually active (aOR = .78, 95% CI: .78-.96), and using effective hormonal birth control (aOR = .7, 95% CI: .56-.88). Exposure to the program was associated with significant reduction in odds of not going to school because of safety concerns (aOR = .87, 95% CI: .78-.97), having experienced forced sex (aOR = .76, 95% CI: .68-.86), ever used marijuana (aOR = .89, 95% CI: .81-.98), and currently using marijuana (aOR = .77, 95% CI: .64-.93). CONCLUSIONS: Exposure to the program was associated with significant decreases in sexual risk behaviors, experience of violence, and substance use.

10.
Theranostics ; 11(18): 8993-9008, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522223

RESUMO

Rationale: Mitochondrial dysfunction facilitates heart failure development forming a therapeutic target, but the mechanism involved remains unclear. We studied whether the Hippo signaling pathway mediates mitochondrial abnormalities that results in onset of dilated cardiomyopathy (DCM). Methods: Mice with DCM due to overexpression of Hippo pathway kinase Mst1 were studied. DCM phenotype was evident in adult animals but contractile dysfunction was identified as an early sign of DCM at 3 weeks postnatal. Electron microscopy, multi-omics and biochemical assays were employed. Results: In 3-week and adult DCM mouse hearts, cardiomyocyte mitochondria exhibited overt structural abnormalities, smaller size and greater number. RNA sequencing revealed comprehensive suppression of nuclear-DNA (nDNA) encoded gene-sets involved in mitochondria turnover and all aspects of metabolism. Changes in cardiotranscriptome were confirmed by lower protein levels of multiple mitochondrial proteins in DCM heart of both ages. Mitochondrial DNA-encoded genes were also downregulated; due apparently to repression of nDNA-encoded transcriptional factors. Lipidomics identified remodeling in cardiolipin acyl-chains, increased acylcarnitine content but lower coenzyme Q10 level. Mitochondrial dysfunction was featured by lower ATP content and elevated levels of lactate, branched-chain amino acids and reactive oxidative species. Mechanistically, inhibitory YAP-phosphorylation was enhanced, which was associated with attenuated binding of transcription factor TEAD1. Numerous suppressed mitochondrial genes were identified as YAP-targets. Conclusion: Hippo signaling activation mediates mitochondrial damage by repressing mitochondrial genes, which causally promotes the development of DCM. The Hippo pathway therefore represents a therapeutic target against mitochondrial dysfunction in cardiomyopathy.

11.
Adv Mater ; : e2104558, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34514641

RESUMO

It is highly desirable to develop compact- and robust-film jumping robots that can withstand severe conditions. Besides, the demands for strong actuation force, large bending curvature in a short response time, and good environmental tolerance are significant challenges to the material design. To address these challenges, this paper reports the fabrication of a thin-film jumping actuator, which exhibits a shrimp-shell architecture, from a conjugated ladder polymer (cLP) that is connected by carbon nanotube (CNT) sheets. The hierarchical porous structure ensures the fast absorption and desorption of organic vapor, thereby achieving a high response rate. The actuator does not exhibit shape distortion at temperatures of up to 225 °C and in concentrated sulfuric acid, as well as when immersed in many organic solvents. This work avails a new design strategy for high-performance actuators that function under harsh and complicated conditions.

12.
Plant Dis ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472972

RESUMO

Maize is a major economic crop worldwide. Maize can be infected by Alternaria species causing leaf blight that can result in significant economic losses. In this study, 168 Alternaria isolates recovered from symptomatic maize leaves were identified based on morphological characteristics, pathogenicity, and multi-locus sequence analyses of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the internal transcribed spacer of ribosomal DNA (rDNA ITS), the RNA polymerase II second largest subunit (RPB2), and histone 3 (HIS3). Maize isolates grouped to four Alternaria species including Alternaria tenuissima, A. alternata, A. burnsii, and Alternaria sp. Notably, A. tenuissima (71.4%) was the most prevalent of the four isolated species, followed by A. alternata (21.5%), Alternaria sp. (4.1%), and A. burnsii (3.0%). Pathogenicity tests showed that all four Alternaria species could produce elliptic to nearly round, or strip lesions on leaves of maize, gray white to dry white in the lesions center and reddish brown in the edge. The average disease incidence (58.47%) and average disease index (63.55) of maize leaves inoculated with A. alternata were significantly higher than levels resulting from A. tenuissima (55.28% and 58.49), Alternaria sp. (55.34% and 58.75), and A. burnsii (56% and 55). Haplotype analyses indicated that there were 14 haplotypes of A. tenuissima and 5 haplotypes of A. alternata in Heilongjiang province and suggested the occurrence of a population expansion. Results of the study showed that Alternaria species associated with maize leaf blight in Heilongjiang province are more diverse than those have been previously reported. This is the first report globally of A. tenuissima, A. burnsii, and an unclassified Alternaria species as causal agents of leaf blight on maize.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34558606

RESUMO

Multiple myeloma (MM) is an incurable disease characterized by malignant plasma cell clonal expansion in the bone marrow; therefore, inhibiting the proliferation of plasma cells is an important approach to overcome the progression of MM. Quercetin (Que) is a promising flavonoid with broad-spectrum anti-tumor activity against various cancers, including MM; however, the underlying mechanism is not yet understood. The present study aimed to reveal the gene expression profile of Que-treated MM cells and clarify its potential mechanism. The 30% inhibitory concentration (IC30) of Que against MM cells was calculated, and the proliferation rate was significantly reduced after Que treatment. Next, 495 dysregulated genes were identified via RNA sequencing in Que-treated MM cells. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses indicated that the dysregulated genes were enriched in various apoptosis-related GO terms and amino acid metabolism-related pathways. qPCR validation showed that protein tyrosine phosphatase receptor-type R (PTPRR) had the highest verified log2 FC (abs) among the top 15 dysregulated genes. Overexpression of PTPRR increased the sensitivity of MM cells against Que, significantly inhibiting their proliferation and colony formation ability; silencing of PTPRR showed the opposite results. Furthermore, bioinformatics analyses and PPI network construction of PTPRR indicated that dephosphorylation of ERK might be the potential pathway for the PTPRR-induced inhibition of MM cell proliferation. In summary, our study identified the gene expression profile in Que-treated MM cells and demonstrated that the upregulation of PTPRR was one of the important mechanisms for the Que-induced inhibition of MM cell proliferation.

14.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 809-813, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511170

RESUMO

OBJECTIVES: To evaluate the accuracy and safety of measurements of transcutaneous carbon dioxide partial pressure (TcPCO2) and transcutaneous oxygen partial pressure (TcPO2) at electrode temperatures lower than the value used in clinical practice in very low birth weight infants. METHODS: A total of 45 very low birth weight infants were enrolled. TcPCO2 and TcPO2 measurements were performed in these infants. Two transcutaneous monitors were placed simultaneously for each subject. One electrode was set and maintained at 42℃ used in clinical practice for neonates (control group), and the other was successively set at 38℃, 39℃, 40°C, and 41℃ (experimental group). The paired t-test was used to compare the measurement results between the groups. A Pearson correlation analysis was used to analyze the correlation between the measurement results of the experimental group and control group, and between the measurement results of experimental group and arterial blood gas parameters. RESULTS: There was no significant difference in TcPCO2 between each experimental subgroup (38-41℃) and the control group. TcPCO2 in each experimental subgroup (38-41℃) was strongly positively correlated with TcPCO2 in the control group (r>0.9, P<0.05) and arterial carbon dioxide partial pressure (r>0.8, P<0.05). There were significant differences in TcPO2 between each experimental subgroup (38-41℃) and the control group (P<0.05), but TcPO2 in each experimental subgroup (38-41℃) was positively correlated with TcPO2 in the control group (r=0.493-0.574, P<0.05) and arterial oxygen partial pressure (r=0.324-0.399, P<0.05). No skin injury occurred during transcutaneous measurements at all electrode temperatures. CONCLUSIONS: Lower electrode temperatures (38-41℃) can accurately measure blood carbon dioxide partial pressure in very low birth weight infants, and thus can be used to replace the electrode temperature of 42°C. Transcutaneous measurements at the lower electrode temperatures may be helpful for understanding the changing trend of blood oxygen partial pressure.


Assuntos
Monitorização Transcutânea dos Gases Sanguíneos , Dióxido de Carbono , Eletrodos , Humanos , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Oxigênio , Pressão Parcial , Temperatura
15.
Bioengineered ; 12(1): 5607-5619, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34515611

RESUMO

Long non-coding RNA (lncRNAs) can participate in gene expression regulation. LINC01296 is abnormally expressed in different tumors and promotes tumorigenesis and development. However, the role of LINC01296 in head and neck squamous cell carcinoma (HNSCC) remains not entirely clear. Thus, to explore LINC01296 expression, biological function and potential mechanism in HNSCC, we used GEPIA and GEO database. QRT-PCR was used to detect the knockout efficiency by LINC01296 inhibition with siRNA. Transwell assay was used to detect the migration and invasion capacity of tumor cells. Then enrichment and immunophenotype correlation analyses were carried out to explore the LINC01296 mechanism in HNSCC. To investigate why LINC01296 was up-regulated in HNSCC, DNA methylation analysis was performed using the DiseaseMeth database. LINC01296 expression was notably up-regulated in HNSCC, which was associated with promoter hypomethylation. Also, it was positively correlated with the HNSCC pathological stage and patients with higher LINC01296 expression levels had a poor prognosis. LINC01296 silencing inhibits HNSCC cell migration and invasion. LINC01296 also participate in the HNSCC progression mainly through protein phosphorylation and microtubule-based process regulation. Overall, LINC01296 was highly expressed in HNSCC, promoted tumor cells' migration and invasion, and might be a potential diagnostic and prognostic marker in HNSCC patients.

17.
Exp Cell Res ; 407(2): 112826, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34508742

RESUMO

INTS6 (integrator complex subunit 6) has been reported as a tumor suppressor in many cancers. However, the expression and biological function of INTS6 in colorectal cancer (CRC) has not been investigated yet. In this study, we found that INTS6 expression was significantly increased in CRC tissues when compared with normal tissues and was associated with poor prognosis. Downregulation of INTS6 induced G1/S-phase cell cycle arrest, and markedly suppressed the growth of CRC cells and the derived tumors, while overexpression of INTS6 showed opposite effect. Mechanism study revealed that INTS6 increased the levels of phosphorylated AKT (p-AKT) and ERK (p-ERK), and the growth-promoting effect of INTS6 was inhibited by AKT and ERK inhibitors. Besides, INTS6 also affected the expression of two targets of PI3K/AKT and MAPK signaling, c-Myc and CDK2, which contributed to cell cycle alteration. Altogether, the present study has revealed the oncogenic role of INTS6 in CRC, providing a novel therapeutic target for this malignant cancer.

18.
PLoS Med ; 18(9): e1003788, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34516565

RESUMO

BACKGROUND: Social innovations in health are inclusive solutions to address the healthcare delivery gap that meet the needs of end users through a multi-stakeholder, community-engaged process. While social innovations for health have shown promise in closing the healthcare delivery gap, more research is needed to evaluate, scale up, and sustain social innovation. Research checklists can standardize and improve reporting of research findings, promote transparency, and increase replicability of study results and findings. METHODS AND FINDINGS: The research checklist was developed through a 3-step community-engaged process, including a global open call for ideas, a scoping review, and a 3-round modified Delphi process. The call for entries solicited checklists and related items and was open between November 27, 2019 and February 1, 2020. In addition to the open call submissions and scoping review findings, a 17-item Social Innovation For Health Research (SIFHR) Checklist was developed based on the Template for Intervention Description and Replication (TIDieR) Checklist. The checklist was then refined during 3 rounds of Delphi surveys conducted between May and June 2020. The resulting checklist will facilitate more complete and transparent reporting, increase end-user engagement, and help assess social innovation projects. A limitation of the open call was requiring internet access, which likely discouraged participation of some subgroups. CONCLUSIONS: The SIFHR Checklist will strengthen the reporting of social innovation for health research studies. More research is needed on social innovation for health.

19.
J Neurosci Methods ; 363: 109353, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34492241

RESUMO

BACKGROUND: The application of deep learning models to electroencephalogram (EEG) signal classification has recently become a popular research topic. Several deep learning models have been proposed to classify EEG signals in patients with various neurological diseases. However, no effective deep learning model for event-related potential (ERP) signal classification is yet available for amnestic mild cognitive impairment (aMCI) with type 2 diabetes mellitus (T2DM). METHOD: This study proposed a single-scale multi-input convolutional neural network (SSMICNN) method to classify ERP signals between aMCI patients with T2DM and the control group. Firstly, the 18-electrode ERP signal on alpha, beta, and theta frequency bands was extracted by using the fast Fourier transform, and then the mean, sum of squares, and absolute value feature of each frequency band were calculated. Finally, these three features are converted into multispectral images respectively and used as the input of the SSMICNN network to realize the classification task. RESULTS: The results show that the SSMICNN can fuse MSI formed by different features, SSMICNN enriches the feature quantity of the neural network input layer and has excellent robustness, and the errors of SSMICNN can be simultaneously transmitted to the three convolution channels in the back-propagation phase. Comparison with Existing Method(s): SSMICNN could more effectively identify ERP signals from aMCI with T2DM from the control group compared to existing classification methods, including convolution neural network, support vector machine, and logistic regression. CONCLUSIONS: The combination of SSMICNN and MSI can be used as an effective biological marker to distinguish aMCI patients with T2DM from the control group.

20.
F1000Res ; 10: 61, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567527

RESUMO

Background: We examined the genetic variants of a Chinese family with a 22-month-old infant with sporadic non-syndromic sensorineural hearing loss (NSHL). Methods: The whole-exome sequence data in the family, especially the de novo variants presented in the patient, were analyzed and the effect of the disease-causing genetic variants on the protein expression level and cellular localization were examined by cell-based functional assay. Results: The infant had no known NSHL-causing variants, except two compound heterozygous variants in connexin26 gene GJB2; one was the c.79G>A, c.341A>G haplotype from the asymptomatic mother which was benign, and the other was a de novo pathogenic c.262G>C (p.A88P). In vitro, GJB2 with c.262G>C was weakly expressed and displayed a punctate distribution in the cytoplasm and cytomembrane, while wild type GJB2 was robustly expressed in the cytomembrane. We deduced that the de novo pathogenic GJB2 c.262G>C exacerbated loss-of-function in the context of leaky variants c.79G>A, c.341A>G in the patient. Interestingly, further analysis of exome sequences revealed that the occurrence of de novo pathogenic variants in the infant was frequent. Among the total~47,000 variants, 143 were de novo in the patient, whereas among all 74 variants predicted to be pathogenic/likely pathogenic, 21 were heterozygous and two were homozygous de novo. The occurrence rate of de novo deleterious variants was much higher (31.1%, 23/74) than that in total (0.34%, 143/47,000). It is notable that most genes with de novo deleterious variants were environment-sensitive, such as GJB2, MNK1, MNK2, MUC4, RAD21 and DNA copy number variations. Conclusions: The full picture of genetic variants in the exome might help us to interpret the NSHL-causing variants. More research is needed into the causes of de novo deleterious variants and gene-environment interactions in congenital NSHL.

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