| 1. |
- Wang, Yangong, et al.
(author)
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Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy
- 2024
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In: NATURE MEDICINE. - 1078-8956 .- 1546-170X. ; 30, s. 1395-1405
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Journal article (peer-reviewed)abstract
- Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making. Using exome sequencing data from one of the largest cohorts of children with cerebral palsy, the genetic diagnostic rates of single-nucleotide and copy number variants were assessed and a sizeable fraction found to be clinically actionable.
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| 2. |
- Yuan-Biao, Qiao, et al.
(author)
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Antifungal resistance-modifying multiplexing action of Momordica charantia protein and phosphorylated derivatives on the basis of growth-dependent gene coregulation in Candida albicans
- 2021
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In: Medical Mycology. - : Oxford University Press. - 1369-3786 .- 1460-2709. ; 59:6, s. 515-527
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Journal article (peer-reviewed)abstract
- Fungal growth-dependent gene coregulation is strongly implicated in alteration of gene-encoding target proteases ruling with an antifungal resistance niche and biology of resistant mutants. On the basis of multialterative processes in this platform, the resistance-modifying strategy is designed in ketoconazole resistant Candida albicans and evaluated with less selective Momordica charantia protein and allosterically phosphorylated derivatives at the Thr102, Thr24 and Thr255 sites, respectively. We demonstrate absolutely chemosensitizing efficacy regarding stepwise-modifying resistance in sensitivity, by a load of only 26.23-40.00 mu g/l agents in Sabouraud's dextrose broth. Five successive modifying-steps realize the decreasing of ketoconazole E-test MIC50 from 11.10 to a lower level than 0.10 mg/l. With the ketoconazole resistance-modifying, colony undergoes a high-frequency morphological switch between high ploidy (opaque) and small budding haploid (white). A cellular event in the first modifying-step associates with relatively slow exponential growth (ie, a 4-h delay)-dependent action, mediated by agents adsorption. Moreover, multiple molecular roles are coupled with intracellularly and extracellularly binding to ATP-dependent RNA helicase dbp6; the 0.08-2.45 fold upregulation of TATA-box-binding protein, rRNA-processing protein and translation initiation factor 5A; and the 7.52-55.33% decrease of cytochrome P450 lanosterol 14 alpha-demethylase, glucan 1, 3-beta glucosidase, candidapepsin-1 and 1-acylglycerol-3-phosphate O-acyltransferase. Spatial and temporal gene coregulation, in the transcription and translation initiation stages with rRNA-processing, is a new coprocessing platform enabling target protease attenuations for resistance-impairing. An updated resistance-modifying measure of these agents in the low-dose antifungal strategic design may provide opportunities to a virtually safe therapy that is in high dose-dependency.
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| 3. |
- Geng, Wenping, et al.
(author)
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Conductive Domain-Wall Temperature Sensors of LiNbO3 Ferroelectric Single-Crystal Thin Films
- 2021
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In: IEEE Electron Device Letters. - : IEEE. - 0741-3106 .- 1558-0563. ; 42:12, s. 1841-1844
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Journal article (peer-reviewed)abstract
- Domain wall current (DWC) plays a key role in storage devices, logic devices and sensors due to its high on-off ratio and nano structure size in the era of nanoelectronics technology. In this work, the DWC of single crystal LiNbO3 thin film was studied by piezoresponse force microscope (PFM) and conducting atomic force microscope (c-AFM). We mainly focus on voltage and temperature dependence of DWC which increases with the voltage and temperatures. Based on this research, the packaged DWC temperature sensor is fabricated and applied in wide temperature range. The existence of domain walls makes the current on-off ratio as high as 103 at the voltage of 15 V. Our study shows that DWC has a negative temperature coefficient (NTC) from 140 K to 500 K. The current increases from 3 pA to 57 μA, which is attributed to the conductivity of switched domain. This work proposes a new type temperature sensor with wide temperature range and high compatibility and sensitivity. In addition, it provides support for harsh environment applications of ferroelectric domain engineering devices.
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