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DUX4 has been widely reported in facioscapulohumeral muscular dystrophy, but its role in Duchenne muscular dystrophy (DMD) is unclear. Dux is the mouse paralog of DUX4. In Dux-/- mdx mice, forelimb grip strength test and treadmill test were performed, and extensor digitorum longus (EDL) contraction properties were measured to assess skeletal muscle function. Pathological changes in mice were determined by serum CK and LDH levels and muscle Masson staining. Inflammatory factors, oxidative stress, and mitochondrial function indicators were detected using kits. Primary muscle satellite cells were isolated, and the antioxidant molecule Nrf2 was detected. MTT assay and Edu assay were used to evaluate proliferation and TUNEL assay for cell death. The results show that the deletion of Dux enhanced forelimb grip strength and EDL contractility, prolonged running time and distance in mdx mice. Deleting Dux also attenuated muscle fibrosis, inflammation, oxidative stress, and mitochondrial dysfunction in mdx mice. Furthermore, Dux deficiency promoted proliferation and survival of muscle satellite cells by increasing Nrf2 levels in mdx mice.
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Proteínas de Homeodominio , Distrofia Muscular de Duchenne , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Animales , Masculino , Ratones , Eliminación de Gen , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Ratones Endogámicos C57BL , Ratones Endogámicos mdx , Ratones Noqueados , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patología , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Células Satélite del Músculo Esquelético/metabolismoRESUMEN
Skyrmions are increasingly favored in developing various spintronic devices as efficient information carriers. The proposed voltage-controlled Dzyaloshinskii-Moriya interaction (VCDM) offers an additional means to manipulate the movement of skyrmions. In this study, we investigated how the skyrmions behave when passing through the VCDM gate in ferromagnetic nanotracks driven by current. Our findings suggest that reducing the strength of the Dzyaloshinskii-Moriya interaction (DMI) can more effectively block skyrmions, while increasing the DMI strength can more effectively attract them. This indicates that the motion behavior of skyrmions can be controlled by changing the shape of the VCDM gate, thereby demonstrating the effectiveness of VCDM gates in controlling skyrmion motion. Due to the ability of VCDM gates to block skyrmions, we have designed a robust subtractor based on skyrmions. These results provide valuable insights for the development of future skyrmion-based devices using the DMI method.
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Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone to various adverse effects due to their strong pharmacological activity and poor receptor selectivity, limiting their application in clinical research. Endocannabinoid hydrolase inhibitors are considered to be the most promising development strategies for the treatment of anxiety disorders. More recent efforts have emphasized that inhibition of two major endogenous cannabinoid hydrolases, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), indirectly activates cannabinoid receptors by increasing endogenous cannabinoid levels in the synaptic gap, circumventing receptor desensitization resulting from direct enhancement of endogenous cannabinoid signaling. In this review, we comprehensively summarize the anxiolytic effects of MAGL and FAAH inhibitors and their potential pharmacological mechanisms, highlight reported novel inhibitors or natural products, and provide an outlook on future directions in this field.
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Amidohidrolasas , Ansiolíticos , Endocannabinoides , Inhibidores Enzimáticos , Monoacilglicerol Lipasas , Humanos , Ansiolíticos/farmacología , Ansiolíticos/química , Amidohidrolasas/antagonistas & inhibidores , Amidohidrolasas/metabolismo , Monoacilglicerol Lipasas/antagonistas & inhibidores , Monoacilglicerol Lipasas/metabolismo , Animales , Endocannabinoides/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/metabolismoRESUMEN
This letter to the editor addresses the study titled "Predictive value of NLR, Fib4, and APRI in the occurrence of liver failure after hepatectomy in patients with hepatocellular carcinoma" by Kuang et al in the World Journal of Gastrointestinal Surgery. The study acknowledges the comprehensive patient data analysis while suggesting that there is a need for further discussion on the clinical applicability of these markers across diverse patient populations. This letter recommends prospective studies for validation and considers the influence of confounding factors. This finding underscores the significance of this study in improving hepatocellular carcinoma management.
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Ancient glass products have suffered from the baptism of time and experienced changes in the burial environment and weathering, resulting in a change in the proportions of their chemical composition and interfering with their accurate identification by later generations. In this paper, the chemical composition of ancient glass products is predicted and identified. First, the multivariate statistical ANOVA test is applied to explore the relationship between whether the cultural relics samples are weathered or not and the glass type, decoration, and color to derive a law of chemical composition of the cultural relics and to analyze the correlation and difference among the four factors. Second, compared with the relevant data of the existing glass products, the missing values are processed by using the method of filling in the plurality. The weathering condition of the sampling points of the samples whose surfaces are not weathered is judged by the "distance discrimination method." Combined with the characteristics of the lead-barium glass and the high-potassium glass, the law of the chemical composition content on the surface of the samples, weathered or not, is explored. The modeling of the gray prediction method was applied again to predict the chemical composition content before weathering. Finally, the generalized Shapley function of fuzzy measurement was used to analyze the correlation between indicators and the chemical compositions and their differences. The scheme proposed in this paper can solve the difficult problem of category judgment in archeology, which is of great significance in promoting the smooth progress of archaeological work.
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Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.
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Secuenciación del Exoma , Humanos , Femenino , Feto/anomalías , Embarazo , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Mutación , Meningomielocele/genética , Meningomielocele/diagnóstico por imagen , Variaciones en el Número de Copia de ADN , Pueblo Asiatico/genética , Pueblos del Este de Asia , Hernia DiafragmáticaRESUMEN
OBJECTIVES: To study the predictive value of hemoglobin (Hb) decrease for the occurrence of necrotizing enterocolitis (NEC) in preterm infants with late-onset sepsis (LOS) . METHODS: Clinical data of 93 LOS preterm infants were collected for retrospective analysis, among which 16 infants developed NEC while 77 infants did not. Based on the decrease in Hb levels from the most recent Hb measurement before LOS occurrence to the initial Hb levels during LOS, the infants were divided into three groups: no Hb decrease (n=15), mild Hb decrease (Hb decrease <15 g/L; n=35), and severe Hb decrease (Hb decrease ≥15 g/L; n=43). Multivariate logistic regression analysis was conducted to explore the predictive factors for NEC secondary to LOS, and the value of Hb decrease in predicting NEC secondary to LOS was evaluated through receiver operating characteristic curve analysis. RESULTS: The incidence of NEC in the severe Hb decrease group, mild Hb decrease group, and no Hb decrease group were 26%, 14%, and 0% (P<0.05), respectively. Multivariate logistic regression analysis revealed that a larger Hb decrease was an independent predictive factor for NEC in LOS preterm infants (OR=1.141, 95%CI: 1.061-1.277, P<0.001). Receiver operating characteristic curve analysis showed that the area under the curve for predicting NEC in preterm infants with LOS using Hb decrease (with a cut-off value of 20 g/L) was 0.803, with sensitivity and specificity of 0.69 and 0.78, respectively. CONCLUSIONS: Hb decrease can serve as an indicator for prediction of NEC in preterm infants with LOS.
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Enterocolitis Necrotizante , Enfermedades del Recién Nacido , Sepsis , Lactante , Recién Nacido , Humanos , Recien Nacido Prematuro , Estudios Retrospectivos , HemoglobinasRESUMEN
The research was carried out to examine the pollution characteristics, ecological risk, and origins of seven heavy metals (Hg, As, Pb, Cu, Cd, Zn, and Ni) in 51 sediment samples gathered from 8 rivers located on the Qinghai-Tibet Plateau (QTP) in China. The contents of Hg and Cd were 5.0 and 1.1 times higher than their background values, respectively. The mean levels of other measured heavy metals were below those found naturally in the local soil. The enrichment factor showed that the study area exhibited significantly enriched Hg with 70.6% sampling sites. The Cd contents at 19.6% of sampling sites were moderately enriched. The other sampling sites were at a less enriched level. The sediments of all the rivers had a medium level of potential ecological risk. Hg was the major ecological risk factor in all sampling sites, followed by Cd. The findings from the positive matrix factorization (PMF) analysis shown agricultural activities, industrial activities, traffic emissions, and parent material were the major sources. The upper, middle, and low reaches of the Quanji river had different Hg isotope compositions, while sediments near the middle reaches were similar to the δ202Hg of the industrial source. At the upstream sampling sites, the Hg isotope content was very close to the background level. The results of this research can establish a strong scientific sound to improve the safety of the natural circumstances of rivers on the QTP.
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Monitoreo del Ambiente , Sedimentos Geológicos , Metales Pesados , Ríos , Contaminantes Químicos del Agua , Metales Pesados/análisis , Sedimentos Geológicos/química , Sedimentos Geológicos/análisis , Ríos/química , Contaminantes Químicos del Agua/análisis , Tibet , Medición de Riesgo , China , Isótopos/análisisRESUMEN
In the majority of occupational settings within China, the concentrations of benzene are observed to fall markedly below the demarcated detection thresholds. Employing traditional risk assessment models, the presence of exceptionally low airborne benzene exposure concentrations may infuse heightened degrees of uncertainty. Consequently, the necessity arises to investigate risk assessment methodologies more apt for the prevalent exposure environment among employees. In the present study, a pharmacokinetic model premised on urinary benzene metabolites (S-PMA and t, t-MA) was employed to ascertain a more precise daily airborne benzene exposure concentration per individual. This value was integrated into the linear multistage model as the 'internal exposure concentration'. In conjunction with the U.S National Environmental Protection Agency's (EPA) inhalation risk assessment model predicated on the external exposure concentration, the Singapore Ministry of Manpower's (MOM) model, and the linear multistage (LMS) model, the carcinogenic and non-carcinogenic effects of benzene were evaluated for 1781 benzene-exposed employees across 76 enterprises in Jiangsu Province. Findings suggest that in the linear multilevel model assessment, the cancer risk levels based on t, t-MA and S-PMA were higher in the printing and recording media reproduction industry, automobile manufacturing industry, general equipment manufacturing industry and the furniture manufacturing industry (median 2.842 × 10-4, 2.819 × 10-4, 2.809 × 10-4, and 2.678 × 10-4), which align more consistently with the actual benzene exposure circumstances of each industry's study participants, with overall risk levels calculated by the linear multistage model exceeding those of the EPA inhalation risk assessment model and the MOM model. This implies that the linear multistage model of internal exposure, based on the reciprocal of benzene biomarkers S-PMA and t, t-MA for airborne benzene exposure, presents enhanced sensitivity and suitability for the current occupational health risk assessment of workers. Without doubt, biomarker-based benzene exposure risk assessment emerges as the optimal choice.
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Benceno , Exposición Profesional , Humanos , Benceno/análisis , Exposición Profesional/análisis , Acetilcisteína , Ácido Sórbico , Biomarcadores/orina , Medición de Riesgo , Monitoreo del Ambiente/métodosRESUMEN
Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by herbal medicines. Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2) and neutrophil extracellular traps (NETs) play important roles in kidney injury and immune defense, respectively, but the mechanism underlying AAN regulation by PSTPIP2 and NETs remains unclear. We found that renal tubular epithelial cell (RTEC) apoptosis, neutrophil infiltration, inflammatory factor, and NET production were increased in a mouse model of AAN, while PSTPIP2 expression was low. Conditional knock-in of Pstpip2 in mouse kidneys inhibited cell apoptosis, reduced neutrophil infiltration, suppressed the production of inflammatory factors and NETs, and ameliorated renal dysfunction. Conversely, downregulation of Pstpip2 expression promoted kidney injury. In vivo, the use of Ly6G-neutralizing antibody to remove neutrophils and peptidyl arginine deiminase 4 (PAD4) inhibitors to prevent NET formation reduced apoptosis, alleviating kidney injury. In vitro, damaged RTECs released interleukin-19 (IL-19) via the PSTPIP2/nuclear factor (NF)-κB pathway and induced NET formation via the IL-20Rß receptor. Concurrently, NETs promoted apoptosis of damaged RTECs. PSTPIP2 affected NET formation by regulating IL-19 expression via inhibition of NF-κB pathway activation in RTECs, inhibiting RTEC apoptosis, and reducing kidney damage. Our findings indicated that neutrophils and NETs play a key role in AAN and therapeutic targeting of PSTPIP2/NF-κB/IL-19/IL-20Rß might extend novel strategies to minimize Aristolochic acid I-mediated acute kidney injury and apoptosis.
Aristolochic acid nephropathy (or AAN for short) is a serious condition affecting the kidneys that is caused by certain traditional Chinese medicines containing a compound called aristolochic acid. This compound is known to have harmful effects on kidney tubular epithelial cells, causing increased inflammation and a form of controlled cell death called apoptosis, which can ultimately lead to organ failure. There is currently no effective treatment for AAN, highlighting the need for a deeper understanding of the mechanisms responsible. Previous studies have shown that immune cells called neutrophils infiltrate the kidneys and damage cells in the early stages of AAN. Neutrophils produce web-like structures called neutrophil extracellular traps, which have been identified as potentially contributing to the damage. A protein called PSTPIP2, which regulates inflammation, has also been shown to contribute to other types of kidney injury. To understand how these inflammatory factors might be involved in AAN, Du, Xu et al. genetically engineered mice to produce extra PSTPIP2 protein specifically in their kidneys. When given aristolochic acid, these mice displayed less kidney damage. Further studies of mouse kidney cells showed that PSTPIP2 protects the kidney by suppressing an inflammatory mechanism that leads to the production of neutrophil extracellular traps. By contrast, in models where PSTPIP2 levels were reduced, neutrophil extracellular traps were shown to cause both apoptosis and kidney injury. The findings of Du, Xu et al. show that neutrophil extracellular traps cause cell damage and apoptosis in a mouse model of AAN and that this action can be reduced by increasing the levels of the protein PSTPIP2. This sheds light on the inflammatory mechanisms behind the kidney damage caused by herbal medicines containing aristolochic acid. Additionally, it opens new avenues for studies aiming to find ways to treat AAN, suggesting that targeting PSTPIP2 could be a promising strategy.
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Lesión Renal Aguda , Ácidos Aristolóquicos , Trampas Extracelulares , Animales , Ratones , FN-kappa B , Lesión Renal Aguda/inducido químicamente , InterleucinasRESUMEN
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders predominantly characterized by impaired corticosteroid synthesis. Clinical phenotypes include hypoadrenocorticism, electrolyte disturbances, abnormal gonadal development, and short stature, of which severe hyponadrenocorticism and salt wasting can be life-threatening. Genetic analysis can help in the clinical diagnosis of CAH. However, the 21-OHD-causing gene CYP21A2 is arranged in tandem with the highly homologous CYP21A1P pseudogene, making it difficult to determine the exact genotypes using the traditional method of multiplex ligation-dependent probe amplification (MLPA) plus Sanger sequencing or next-generation sequencing (NGS). We applied a long-read sequencing-based approach termed comprehensive analysis of CAH (CACAH) to 48 newborns with CAH that were diagnosed by clinical features and the traditional MLPA plus Sanger sequencing method for retrospective analysis, to evaluate its efficacy in the clinical diagnosis of neonatal CAH. Compared with the MLPA plus Sanger sequencing method, CACAH showed 100 % consistency in detecting SNV/indel variants located in exons and exon-intron boundary regions of CAH-related genes. It can directly determine the cis-trans relationship without the need to analyze parental genotypes, which reduces the time to diagnosis. Moreover, CACAH was able to distinguish different CYP21A1P/CYP21A2 and TNXA/TNXB chimeras, and detect additional variants (CYP21A2 variants c.-121C > T, c.*13G > A, c.*52C > T, c.*440C > T, c.*443 T > C, and TNXB variants c.12463 + 2 T > C, c.12204 + 5G > A). We also identified the TNXB variant c.11435_11524 + 30del alone instead of as a part of the TNXA/TNXB-CH-1 chimera in two newborns, which might be introduced by gene conversion. All of these characteristics enabled clinicians to better explain the phenotype of subjects and manage them more effectively. CACAH has a great advantage over the traditional MLPA and Sanger sequencing methods, showing substantial potential in the genetic diagnosis and screening of neonatal CAH.
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Hiperplasia Suprarrenal Congénita , Enanismo , Recién Nacido , Humanos , Hiperplasia , Estudios Retrospectivos , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Tenascina , Esteroide 21-Hidroxilasa/genéticaRESUMEN
Composed query image retrieval task aims to retrieve the target image in the database by a query that composes two different modalities: a reference image and a sentence declaring that some details of the reference image need to be modified and replaced by new elements. Tackling this task needs to learn a multimodal embedding space, which can make semantically similar targets and queries close but dissimilar targets and queries as far away as possible. Most of the existing methods start from the perspective of model structure and design some clever interactive modules to promote the better fusion and embedding of different modalities. However, their learning objectives use conventional query-level examples as negatives while neglecting the composed query's multimodal characteristics, leading to the inadequate utilization of the training data and suboptimal construction of metric space. To this end, in this paper, we propose to improve the learning objective by constructing and mining hard negative examples from the perspective of multimodal fusion. Specifically, we compose the reference image and its logically unpaired sentences rather than paired ones to create component-level negative examples to better use data and enhance the optimization of metric space. In addition, we further propose a new sentence augmentation method to generate more indistinguishable multimodal negative examples from the element level and help the model learn a better metric space. Massive comparison experiments on four real-world datasets confirm the effectiveness of the proposed method.
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Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.
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Trastorno Depresivo Mayor , Estudio de Asociación del Genoma Completo , Humanos , Predisposición Genética a la Enfermedad , Trastorno Depresivo Mayor/genética , Depresión , Mapeo Cromosómico , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
BACKGROUND AND PURPOSE: Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by using herbal medicines. Currently, no therapies are available to treat or prevent aristolochic acid nephropathy. Histone deacetylase (HDAC) plays a crucial role in the development and progression of renal disease. We tested whether HDAC inhibitors could prevent aristolochic acid nephropathy and determined the underlying mechanism. EXPERIMENTAL APPROACH: HDACs expression in the aristolochic acid nephropathy model was examined. The activation of PANoptosis of mouse kidney and renal tubular epithelial cell were assessed after exposure to HDAC1 and HDAC2 blockade. Kidney-specific knock-in of proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) mice were used to investigate whether PSTPIP2 affected the production of PANoptosome. KEY RESULTS: Aristolochic acid upregulated the expression of HDAC1 and HDAC2 in the kidneys. Notably, the HDAC1 and HDAC2 specific inhibitor, romidepsin (FK228, depsipeptide), suppressed aristolochic acid-induced kidney injury, epithelial cell pyroptosis, apoptosis and necroptosis (PANoptosis). Moreover, romidepsin upregulated PSTPIP2 in renal tubular epithelial cells, which was enhanced by aristolochic acid treatment. Conditional knock-in of PSTPIP2 in the kidney protected against aristolochic acid nephropathy. In contrast, the knockdown of PSTPIP2 expression in PSTPIP2-knock-in mice restored kidney damage and PANoptosis. PSTPIP2 function was determined in vitro using PSTPIP2 knockdown or overexpression in mouse renal tubular epithelial cells (mTECs). Additionally, PSTPIP2 was found to regulate caspase 8 in aristolochic acid nephropathy. CONCLUSION AND IMPLICATIONS: HDAC-mediated silencing of PSTPIP2 may contribute to aristolochic acid nephropathy. Hence, HDAC1 and HDAC2 specific inhibitors or PSTPIP2 could be valuable therapeutic agents for preventing aristolochic acid nephropathy.
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Ácidos Aristolóquicos , Enfermedades Renales , Ratones , Animales , Piroptosis , Histona Desacetilasas/metabolismo , Necroptosis , Enfermedades Renales/metabolismo , Ácidos Aristolóquicos/toxicidad , Apoptosis , Histona Desacetilasa 2/genética , Histona Desacetilasa 2/metabolismoRESUMEN
BACKGROUND: Symptoms of major depressive disorder (MDD) are commonly assessed using self-rating instruments like the Patient Health Questionnaire-9 (PHQ-9) (current symptoms) and the Composite International Diagnostic Interview Short-Form (CIDI-SF) (worst-episode symptoms). We performed a systematic comparison between them for their genetic architecture and utility in investigating MDD heterogeneity. METHODS: Using data from the UK Biobank (n = 41,948-109,417), we assessed the single nucleotide polymorphism heritability and genetic correlation (rg) of both sets of MDD symptoms. We further compared their rg with non-MDD traits and used Mendelian randomization to assess whether either set of symptoms has more genetic sharing with non-MDD traits. We also assessed how specific each set of symptoms is to MDD using the metric polygenic risk score pleiotropy. Finally, we used genomic structural equation modeling to identify factors that explain the genetic covariance between each set of symptoms. RESULTS: Corresponding symptoms reported through the PHQ-9 and CIDI-SF have low to moderate genetic correlations (rg = 0.43-0.87), and this cannot be fully attributed to different severity thresholds or the use of a skip structure in the CIDI-SF. Both Mendelian randomization and polygenic risk score pleiotropy analyses showed that PHQ-9 symptoms are more associated with traits that reflect general dysphoria, whereas the skip structure in the CIDI-SF allows for the identification of heterogeneity among likely MDD cases. Finally, the 2 sets of symptoms showed different factor structures in genomic structural equation modeling, reflective of their genetic differences. CONCLUSIONS: MDD symptoms assessed using the PHQ-9 and CIDI-SF are not interchangeable; the former better indexes general dysphoria, while the latter is more informative about within-MDD heterogeneity.
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The microscopic mechanisms underpinning the spontaneous surface passivation of metals from ubiquitous water have remained largely elusive. Here, using in situ environmental electron microscopy to atomically monitor the reaction dynamics between aluminum surfaces and water vapor, we provide direct experimental evidence that the surface passivation results in a bilayer oxide film consisting of a crystalline-like Al(OH)3 top layer and an inner layer of amorphous Al2O3. The Al(OH)3 layer maintains a constant thickness of ~5.0 Å, while the inner Al2O3 layer grows at the Al2O3/Al interface to a limiting thickness. On the basis of experimental data and atomistic modeling, we show the tunability of the dissociation pathways of H2O molecules with the Al, Al2O3, and Al(OH)3 surface terminations. The fundamental insights may have practical significance for the design of materials and reactions for two seemingly disparate but fundamentally related disciplines of surface passivation and catalytic H2 production from water.
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Magnetic skyrmions are considered promising candidates for use as information carriers in future spintronic devices. To achieve the development of skyrmion-based spintronic devices, a reasonable and feasible nanotrack is essential. In this paper, we conducted a study on the current-driven skyrmion movement in a circular-ring-shaped nanotrack. Our results suggest that the asymmetry of the inside and outside boundary of the circular ring changed the stable position of the skyrmion, causing it to move like the skyrmion Hall effect when driven by currents. Moreover, the asymmetric boundaries have advantages in enhancing or weakening the skyrmion Hall effect. Additionally, we also compared the skyrmion Hall effect from the asymmetric boundary of circular-ring nanotracks with that from the inhomogeneous Dzyaloshinskii-Moriya interaction. It was found that the skyrmion Hall effect in the circular ring is significantly greater than that caused by the inhomogeneous Dzyaloshinskii-Moriya interaction. These results contribute to our understanding of the skyrmion dynamics in confined geometries and offer an alternative method for controlling the skyrmion Hall effect of skyrmion-based devices.
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Biobanks that collect deep phenotypic and genomic data across many individuals have emerged as a key resource in human genetics. However, phenotypes in biobanks are often missing across many individuals, limiting their utility. We propose AutoComplete, a deep learning-based imputation method to impute or 'fill-in' missing phenotypes in population-scale biobank datasets. When applied to collections of phenotypes measured across ~300,000 individuals from the UK Biobank, AutoComplete substantially improved imputation accuracy over existing methods. On three traits with notable amounts of missingness, we show that AutoComplete yields imputed phenotypes that are genetically similar to the originally observed phenotypes while increasing the effective sample size by about twofold on average. Further, genome-wide association analyses on the resulting imputed phenotypes led to a substantial increase in the number of associated loci. Our results demonstrate the utility of deep learning-based phenotype imputation to increase power for genetic discoveries in existing biobank datasets.
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Aprendizaje Profundo , Estudio de Asociación del Genoma Completo , Humanos , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Bancos de Muestras Biológicas , Polimorfismo de Nucleótido Simple , FenotipoRESUMEN
Biobanks often contain several phenotypes relevant to diseases such as major depressive disorder (MDD), with partly distinct genetic architectures. Researchers face complex tradeoffs between shallow (large sample size, low specificity/sensitivity) and deep (small sample size, high specificity/sensitivity) phenotypes, and the optimal choices are often unclear. Here we propose to integrate these phenotypes to combine the benefits of each. We use phenotype imputation to integrate information across hundreds of MDD-relevant phenotypes, which significantly increases genome-wide association study (GWAS) power and polygenic risk score (PRS) prediction accuracy of the deepest available MDD phenotype in UK Biobank, LifetimeMDD. We demonstrate that imputation preserves specificity in its genetic architecture using a novel PRS-based pleiotropy metric. We further find that integration via summary statistics also enhances GWAS power and PRS predictions, but can introduce nonspecific genetic effects depending on input. Our work provides a simple and scalable approach to improve genetic studies in large biobanks by integrating shallow and deep phenotypes.
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Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/genética , Predisposición Genética a la Enfermedad , Bancos de Muestras Biológicas , Estudio de Asociación del Genoma Completo , Herencia Multifactorial/genética , Fenotipo , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Objective: Based on the Montreux definition, we aim to develop and validate a predictive model for the early diagnosis of neonatal acute respiratory distress syndrome (ARDS). Methods: A retrospective analysis of clinical data on 198 neonates with respiratory distress from January 2018 to January 2022 was conducted. Neonates meeting Montreux definition were classified as ARDS group (n = 79), while the rest were non-ARDS group (n = 119). Univariate analysis identified indicators for neonatal ARDS, followed by logistic regression to construct a predictive model for early diagnosis. The ability of predictors and models to predict neonatal ARDS was evaluated using area under the curve (AUC), and model performance was estimated through bootstrap resampling. Results: Maternal prenatal fever, abnormal fetal heart beat, meconium-stained amniotic fluid (MSAF), white blood cell (WBC), absolute neutrophil count (ANC), neutrophil percentage (NE%), platelet count (PLT), C-reactive protein (CRP), procalcitonin (PCT), creatine kinase (CK), activated partial thromboplastin time (APTT), serum calcium (Ca) and sodium (Na)exhibited significant differences between the ARDS group and the non-ARDS group (P < 0.05). MSAF (OR=5.037; 95% CI: 1.523-16.657; P < 0.05), ANC (OR = 1.324; 95% CI: 1.172-1.495; P < 0.05), PLT (OR = 0.979; 95% CI: 0.971-0.986; P < 0.05), Ca (OR = 0.020; 95% CI: 0.004-0.088; P < 0.05) emerged as independent risk factors for the development of ARDS. The respective AUC values for MSAF, ANC, PLT, Ca, and the combined prediction models were 0.606, 0.691, 0.808, 0.761 and 0.931. Internal validation showed that the C-index for the model was 0.931. Conclusions: Early application of the model combining MSAF, ANC, PLT and Ca may have a good predictive effect on the early diagnosis of neonatal ARDS.