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More than 90% of genetic variants are rare in most modern sequencing studies, such as the Alzheimer's Disease Sequencing Project (ADSP) whole-exome sequencing (WES) data. Furthermore, 54% of the rare variants in ADSP WES are singletons. However, both single variant and unit-based tests are limited in their statistical power to detect an association between rare variants and phenotypes. To best use missense rare variants and investigate their biological effect, we examine their association with phenotypes in the context of protein structures. We developed a protein structure-based approach, protein optimized kernel evaluation of missense nucleotides (POKEMON), which evaluates rare missense variants based on their spatial distribution within a protein rather than their allele frequency. The hypothesis behind this test is that the three-dimensional spatial distribution of variants within a protein structure provides functional context to power an association test. POKEMON identified three candidate genes (TREM2, SORL1, and EXOC3L4) and another suggestive gene from the ADSP WES data. For TREM2 and SORL1, two known Alzheimer's disease (AD) genes, the signal from the spatial cluster is stable even if we exclude known AD risk variants, indicating the presence of additional low-frequency risk variants within these genes. EXOC3L4 is a novel AD risk gene that has a cluster of variants primarily shared by case subjects around the Sec6 domain. This cluster is also validated in an independent replication data set and a validation data set with a larger sample size.
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Doença de Alzheimer , Doença de Alzheimer/genética , Frequência do Gene , Predisposição Genética para Doença , Humanos , Proteínas Relacionadas a Receptor de LDL/genética , Proteínas Relacionadas a Receptor de LDL/metabolismo , Proteínas de Membrana Transportadoras/genética , Mutação de Sentido Incorreto , Fenótipo , Sequenciamento do ExomaRESUMO
Aqueous zinc metal batteries are a viable candidate for next-generation energy storage systems, but suffer from poor cycling efficiency of the Zn anode. Emerging approaches aim to regulate zinc plating behavior to suppress uncontrolled dendrites, while the stripping process is seldom considered. Herein, an oriented metal stripping strategy is demonstrated to stabilize the Zn anode by removing high-index facets for exposing the (002) plane through the addition of anionic additive sodium citrate (SC). Consequently, high-index facets that coordinate strongly with SC are preferentially stripped out due to a reduced stripping barrier, rendering stable (002) facet preponderant in epitaxial plating. After repeat stripping/plating, the ultra-high proportion of 93% for (002) and large-size grains of ≈100 µm (six times larger than before) can be obtained. Zn anode shows continuous 25 000 cycles with low overpotential at 100 mA cm-2 in symmetric cells and more than 70 h of stable operation even at an ultra-high depth of discharge of 92.3%. Moreover, an extremely long lifespan of 12 000 cycles at 10 A g-1 with a high capacity retention of 89% is achieved by the assembled Zn//I2 battery. This work provides a distinctive approach to improving the stripping process to design highly efficient zinc anodes for promising aqueous zinc metal batteries.
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Perovskite solar cell (PSC) is a promising photovoltaic technology that achieves over 26% power conversion efficiency (PCE). However, the high materials costs, complicated fabrication process, as well as poor long-term stability, are stumbling blocks for the commercialization of the PSCs in normal structures. The hole transport layer (HTL)-free carbon-based PSCs (C-PSCs) are expected to overcome these challenges. However, C-PSCs have suffered from relatively low PCE due to severe energy loss at the perovskite/carbon interface. Herein, the study proposes to boost the hole extraction capability of carbon electrode by incorporating functional manganese (II III) oxide (Mn3O4). It is found that the work function (WF) of the carbon electrode can be finely tuned with different amounts of Mn3O4 addition, thus the interfacial charge transfer efficiency can be maximized. Besides, the mechanical properties of carbon electrode can also be strengthened. Finally, a PCE of 19.03% is achieved. Moreover, the device retains 90% of its initial PCE after 2000 h of storage. This study offers a feasible strategy for fabricating efficient paintable HTL-free C-PSCs.
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Although many studies have discussed the impact of Europe's air quality, very limited research focused on the detailed phenomenology of ambient trace elements (TEs) in PM10 in urban atmosphere. This study compiled long-term (2013-2022) measurements of speciation of ambient urban PM10 from 55 sites of 7 countries (Switzerland, Spain, France, Greece, Italy, Portugal, UK), aiming to elucidate the phenomenology of 20 TEs in PM10 in urban Europe. The monitoring sites comprised urban background (UB, n = 26), traffic (TR, n = 10), industrial (IN, n = 5), suburban background (SUB, n = 7), and rural background (RB, n = 7) types. The sampling campaigns were conducted using standardized protocols to ensure data comparability. In each country, PM10 samples were collected over a fixed period using high-volume air samplers. The analysis encompassed the spatio-temporal distribution of TEs, and relationships between TEs at each site. Results indicated an annual average for the sum of 20 TEs of 90 ± 65 ng/m3, with TR and IN sites exhibiting the highest concentrations (130 ± 66 and 131 ± 80 ng/m3, respectively). Seasonal variability in TEs concentrations, influenced by emission sources and meteorology, revealed significant differences (p < 0.05) across all monitoring sites. Estimation of TE concentrations highlighted distinct ratios between non-carcinogenic and carcinogenic metals, with Zn (40 ± 49 ng/m3), Ti (21 ± 29 ng/m3), and Cu (23 ± 35 ng/m3) dominating non-carcinogenic TEs, while Cr (5 ± 7 ng/m3), and Ni (2 ± 6 ng/m3) were prominent among carcinogenic ones. Correlations between TEs across diverse locations and seasons varied, in agreement with differences in emission sources and meteorological conditions. This study provides valuable insights into TEs in pan-European urban atmosphere, contributing to a comprehensive dataset for future environmental protection policies.
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Mycotoxins, ubiquitous contaminants in food, present a global threat to human health and well-being. Mitigation efforts, such as the implementation of sound agricultural practices, thorough food processing, and the advancement of mycotoxin control technologies, have been instrumental in reducing mycotoxin exposure and associated toxicity. To comprehensively assess mycotoxins and their toxicodynamic implications, the deployment of effective and predictive strategies is imperative. Understanding the manner of action, transformation, and cumulative toxic effects of mycotoxins, moreover, their interactions with food matrices can be gleaned through gene expression and transcriptome analyses at cellular and molecular levels. MicroRNAs (miRNAs) govern the expression of target genes and enzymes that play pivotal roles in physiological, pathological, and toxicological responses, whereas acute phase proteins (APPs) exert regulatory control over the metabolism of therapeutic agents, both endogenously and posttranscriptionally. Consequently, this review aims to consolidate current knowledge concerning the regulatory role of miRNAs in the initiation of toxicological pathways by mycotoxins and explores the potential of APPs as biomarkers following mycotoxin exposure. The findings of this research highlight the potential utility of miRNAs and APPs as indicators for the detection and management of mycotoxins in food through biological processes. These markers offer promising avenues for enhancing the safety and quality of food products.
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MicroRNAs , Micotoxinas , Humanos , Micotoxinas/análise , MicroRNAs/genética , Contaminação de Alimentos/análise , Proteínas de Fase AgudaRESUMO
Photoactive black-phase formamidinium lead triiodide (α-FAPbI3) perovskite has dominated the prevailing high-performance perovskite solar cells (PSCs), normally for those spin-coated, conventional n-i-p structured devices. Unfortunately, α-FAPbI3 has not been made full use of its advantages in inverted p-i-n structured PSCs fabricated via blade-coating techniques owing to uncontrollable crystallization kinetics and complicated phase evolution of FAPbI3 perovskites during film formation. Herein, a customized crystal surface energy regulation strategy has been innovatively developed by incorporating 0.5â mol % of N-aminoethylpiperazine hydroiodide (NAPI) additive into α-FAPbI3 crystal-derived perovskite ink, which enabled the formation of highly-oriented α-FAPbI3 films. We deciphered the phase transformation mechanisms and crystallization kinetics of blade-coated α-FAPbI3 perovskite films via combining a series of in-situ characterizations and theoretical calculations. Interestingly, the strong chemical interactions between the NAPI and inorganic Pb-I framework help to reduce the surface energy of (100) crystal plane by 42 %, retard the crystallization rate and lower the formation energy of α-FAPbI3. Benefited from multifaceted advantages of promoted charge extraction and suppressed non-radiative recombination, the resultant blade-coated inverted PSCs based on (100)-oriented α-FAPbI3 perovskite films realized promising efficiencies up to 24.16 % (~26.5 % higher than that of the randomly-oriented counterparts), accompanied by improved operational stability. This result represented one of the best performances reported to date for FAPbI3-based inverted PSCs fabricated via scalable deposition methods.
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The practical application of aqueous zinc batteries are highly limited by unsatisfied Zn anodes for the unavoidable dendrite growth and side reactions. Crystal orientation engineering is an effective way to overcome these inherent drawbacks. However, how to achieve Zn plating with manipulated crystallographic orientation is still a great challenge. Herein, a uniform (002)-oriented Zn metal anode is reported based on a directional cation recognition and crystal assembly strategy. The activated layered double hydroxide (Act-LDH) exhibits favorable adsorption energy with Zn2+ and high lattice matching with Zn (002) plane, which can be served as directional recognition layer to anchor Zn2+ and regulate crystallographic orientation of Zn as well. As demonstration, Zn crystals with ultrahigh ratio of (002)/(100) plane of 15.7 are assembled parallelly on horizontal Act-LDH, in which high CE of 99.85% maintains over 18 000 cycles. The symmetric battery with (002)-oriented Zn shows stable plating/stripping process over 1650 and 420 h at 1 mA cm-2 /0.5 mA h cm-2 and 10 mA cm-2 /5 mA h cm-2 , respectively, which is 9 and 12 times higher than unoriented polycrystalline Zn. Moreover, as-assembled full battery displays high specific capacity of 120 mA h g-1 at 2 A g-1 over 1800 cycles.
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BACKGROUND: Pediatric pulmonary hypertension (PH) is a serious and rare disease that is often derived from genetic mutations. Kabuki syndrome (KS) is a chromosomal abnormality disease that has its origin in the mutation of lysine methyltransferase 2D(KMT2D). Recent evidence has shown that KMT2D mutations are associated with pediatric pulmonary disorders. However, the relationship between the clinical courses of PH and the KMT2D mutation is reported in extremely few cases. Therefore, in this paper, a case was presented and previous literature was reviewed for better understanding of the correlation between pediatric PH and KMT2D mutations. CASE PRESENTATION: A 3-year-old girl was transferred to our center for severe cough, shortness of breath, fatigue and fever. Physical examination revealed facial deformities and growth retardation. Echocardiography showed a small atrial septal defect (ASD), and right heart catheterization indicated a significant increase in pulmonary vascular pressure and resistance. The genetic test suggested that she had a KMT2D gene mutation. The patient was finally diagnosed with KS. She was given targeted drugs to reduce pulmonary vascular pressure, but the effect was unsatisfactory. CONCLUSIONS: KS can be complicated with multiple organ malformations and dysfunction. With the progress of next generation sequencing, an increasing number of new phenotypes related to KMT2D mutations have been reported. A bold hypothesis is proposed in this article, that is, PH may be a new phenotype associated with KMT2D mutations. It is suggested that KS and PH should be differentiated from each other to avoid delayed diagnosis and treatment in clinical practice. There is no specific drug for KS treatment. The prognosis of children with inherited PH is usually poor, and lung transplantation may increase their survival rates.
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Anormalidades Múltiplas , Hipertensão Pulmonar , Humanos , Feminino , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/genética , Fenótipo , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Testes GenéticosRESUMO
Protein function can be impacted by changes in protein structure stability, but determining which change has impact is complex. Stability can be affected by a large change in the tertiary (3D) structure of the protein or due to free-energy changes caused by single amino acid substitutions. Changes in the DNA sequence can have minor or major impact on protein stability, which can lead to disease. Inherited retinal degenerations are generally caused by single mutations which are mostly located in protein-coding regions, while age-related macular degeneration (AMD) is a complex disorder that can be influenced by some genetic variants impacting proteins involved in the disease, although not all AMD risk variants lead to amino acid changes. Here, we review ways that proteins may be affected, the identification and understanding of these changes, and how to identify causal changes that can be targeted to develop treatments to alleviate retinal degenerative disease.
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Degeneração Macular , Degeneração Retiniana , Humanos , Degeneração Retiniana/genética , Retina , Degeneração Macular/genética , Mutação , Proteínas/química , Estabilidade ProteicaRESUMO
Canopy interception loss affects the local water budget by removing a non-negligible proportion of rainfall from the terrestrial surface. Thus, quantifying interception loss is essential for thoroughly understanding the role of vegetation in the local hydrological cycle, especially in dryland ecosystems. However, sparse shrubs in dryland ecosystems have not been sufficiently studied, owing to time- and labor-intensive field experiments and challenging model parameterization. In this work, 4-year growing season field experiments on rainfall partitioning were conducted for three dominant shrub species (Haloxylon ammodendron, Nitraria sphaerocarpa, and Calligonum mongolicum) in an oasis-desert ecotone in northwestern China. The revised Gash analytical model was well parameterized, which reliably simulated the cumulative interception loss for sparse shrubs, and the validated model performed better for H. ammodendron, followed by C. mongolicum and N. sphaerocarpa, with relative errors of 8.4%, 15.4%, and 23.9%, respectively. The mean individual interception loss percentage for H. ammodendron (28.4%) was significantly higher than that for C. mongolicum (11.0%) and N. sphaerocarpa (10.9%) (p < 0.05), which could be ascribed to the higher canopy storage capacity and wet-canopy evaporation rate of H. ammodendron. For all shrub species, the majority proportion of interception loss occurred during canopy saturation and drying-out periods, accounting for approximately 79-85% of the cumulative interception loss. Overall, the mean local interception loss of three dominant shrub species in the ecotone removed nearly 17% of the corresponding cumulative rainfall during the growing season. These results not only provide methodological references for estimating the interception loss of sparse vegetation in dryland ecosystems, but also provide scientific insights for water resource management and ecosystem restoration in water-limited regions similar to the experimental site.
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Chenopodiaceae , Fabaceae , Ecossistema , Chuva , Movimentos da Água , ÁguaRESUMO
Surface states are one of the crucial factors determining the phase stability of formamidinium-based perovskites. Compared with other compositions, exclusive lattice strain in FAPbI3 perovskite generates defects at the surface more readily, making them more vulnerable at the surface and easier to trigger the phase transition from α-phase to the non-perovskite δ-phase. In order to regulate the surface quality, here, a chemi-mechanical cleavage approach is reported, i.e., tape peel-zone (PZ), implemented by attaching and peeling off the ordinary Kapton Tapes. The PZ approach can simultaneously eliminate the surface defects of perovskite and siliconize the film surface with hydrophobic silicone compounds. These two functionalities endow α-FAPbI3 perovskite with a robust hydrophobic surface, which can sustain for 30 days under a relative humidity of 60% and withstand the high temperature up to 240 °C. The unencapsulated PZ-treated cells show 80.3% of initial performance after 90 h of continuous operation in ambient air, which is 31.4 times more stable than the pristine cell.
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Wood-based solar steam evaporators have been attracting increasing interest due to their great potential for addressing water scarcity by utilizing sustainable materials and energy. However, engineering a 3D porous structure within the wood lumens and its effect on solar vapor evaporation have not yet been well explored. Here, a natural wood-based solar evaporator with hierarchical pores is fabricated by assembling polyvinyl alcohol within the lumens through an ice-templating approach. The polyvinyl alcohol porous network is engineered from vertically aligned microchannels to dendritically bridged pores with a narrowed size of a few micrometers and significantly increased surface area. Although the formation of plenty of microscopic channels increases the capillary force in comparison to the native wood lumen, the morphology change induces a high tortuosity factor of the porous structure, resulting in a reduced water transportation rate as well as an increased contact angle. On the other hand, the high surface area of the engineered wood lumens and the good hydrophilicity of the filled polyvinyl alcohol improve the ratio of the formed intermediate water, contributing to reduced vaporization enthalpy. Consequently, by using polydopamine as the photothermal material, the hierarchically structured polyvinyl alcohol-wood solar evaporator exhibits an evaporation rate of 1.6 kg m-2 h-1 under 1 sun irradiation and a high solar evaporation efficiency of up to 107%, which are higher than most of the reported natural-wood-based solar evaporators. Moreover, by exploring the correlation between porous morphology and performance, it has been found that the polyvinyl alcohol-wood composite not only presents an inexpensive and sustainable evaporator but also provides guidelines for designing high-performance steam generation devices.
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Zearalenone (ZEN) contamination of various foods and feeds is an important global problem. In some animals and humans, ZEN causes significant health issues in addition to massive economic losses, annually. Therefore, removal or degradation of the ZEN in foods and feeds is required to be done. The conventional physical and chemical methods have some serious issues including poor efficiency, decrease in nutritional value, palatability of feed, and use of costly equipment. Research examined microbes from diverse media for their ability to degrade zearalenone and other toxins, and the findings of several investigations revealed that enzymes produced from microbes play a significant role in the degradation of mycotoxins. In established bacterial hosts, genetically engineered technique was used to enhance heterologously produced degrading enzymes. Then, the bio-degradation of ZEN by the use of micro-organisms or their enzymes is much more advantageous and is close to nature and ecofriendly. Furthermore, an effort is made to put forward the work done by different scientists on the biodegradation of ZEN by the use of fungi, yeast, bacteria, and/or their enzymes to degrade the ZEN to non-toxic products. KEY POINTS: â¢Evolved microbial strains degraded ZEA more quickly â¢Different degrading properties were studied.
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Micotoxinas , Zearalenona , Animais , Alimentos , Contaminação de Alimentos , Micotoxinas/metabolismo , Saccharomyces cerevisiae/metabolismo , Zearalenona/metabolismoRESUMO
BACKGROUND: To assess the interaction of sleep duration and depression on the risk of cardiovascular disease (CVD). METHODS: A total of 13,488 eligible participants were enrolled in this retrospective cohort study eventually. Baseline characteristics were extracted from the China Health and Retirement Longitudinal Study (CHARLS) database, including age, sex, diabetes, high-density lipoprotein (HDL), blood glucose (GLU), glycosylated hemoglobin (GHB) etc. Univariate and multivariate negative binomial regression models were carried out to assess the statistical correlation of sleep duration and depression on CVD separately. Additionally, multivariate negative binomial regression model was used to estimate the interaction of sleep duration and depression on CVD risk. RESULTS: After adjusting for age, sex, educational background, hypertension, diabetes, dyslipidemia, the use of hypnotics, disability, nap, drinking, deposit, sleep disturbance, HDL, triglyceride, total cholesterol, GLU and GHB, the risk of CVD in participants with the short sleep duration was increased in comparison with the normal sleep duration [relative risk (RR)=1.02, 95% confidence interval (CI):1.01-1.03]; compared to the participants with non-depression, participants suffered from depression had an increased risk of CVD (RR=1.05, 95%CI:1.04-1.06). Additionally, the result also suggested that the interaction between short sleep duration and depression on the risk of CVD was statistically significant in these patients with diabetes and was a multiplicative interaction. CONCLUSION: An interaction between short sleep duration and depression in relation to an increased risk of CVD among Chinese middle-aged and elderly individuals was noticed, which may provide a reference that people with diabetes should focus on their sleep duration and the occurrence of depression, and coexisting short sleep duration and depression may expose them to a higher risk of CVD.
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Doenças Cardiovasculares , Depressão , Transtornos do Sono-Vigília , Idoso , Glicemia , Doenças Cardiovasculares/epidemiologia , Colesterol , Depressão/complicações , Hemoglobinas Glicadas , Humanos , Lipoproteínas HDL , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sono , TriglicerídeosRESUMO
Aflatoxin B1 (AFB1) contamination in feed and food seriously threatens the healthy growth of animals and humans, and it may lead to huge economic losses in livestock and poultry production. Therefore, screening of high-efficient AFB1-degrading bacteria is necessary to ensure the safety of feed and food. The study aims to isolate and characterize bacteria from various sources to explore its AFB1 degradation potential. Fifteen bacterial were obtained using a medium containing coumarin as the sole carbon source; only one strain showed a good-degrading ability in culture media by adding AFB1 and it was selected for further studies. A gram-negative and spore-forming, designated E1, was identified as Paenibacillus pabuli, with the highest sequence similarity to P. pabuli NBRC13638T (98.97%). The growth of the strain E1 was observed under 22-47 °C, pH 5.5-9.5 and NaCl concentration 0-6% (w/v), with optimum growth at 37 °C, pH 7.5 and 1% NaCl. The biodegradation characteristics of object strain were detected by high performance liquid chromatography (HPLC). The degradation ratio of AFB1 reached 55% at 24 h and 70.2% at 48 h. After 96 h, the degradation rate of AFB1 reached 85.9%. The active degradation components were present in the cell-free supernatant of strain E1, and the degradation ratio of AFB1 reached 80.0% after 96 h. It is the first report that genus Paenibacillus could degrade AFB1. Moreover, E1 has highly adaptable to diverse environmental conditions. It will be a potential candidate for biodegradation of mycotoxins in feed and food.
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Aflatoxina B1 , Paenibacillus , Animais , Biodegradação Ambiental , Meios de Cultura , Humanos , Paenibacillus/genéticaRESUMO
How muscles are used is a key to understanding the internal driving of fish swimming. However, the underlying mechanisms of some features of the muscle activation patterns and their differential appearance in different species are still obscure. In this study, we explain the muscle activation patterns by using 3D computational fluid dynamics models coupled to the motion of fish with prescribed deformation and examining the torque and power required along the fish body with two primary swimming modes. We find that the torque required by the hydrodynamic forces and body inertia exhibits a wave pattern that travels faster than the curvature wave in both anguilliform and carangiform swimmers, which can explain the traveling wave speeds of the muscle activations. Notably, intermittent negative power (i.e., power delivered by the fluid to the body) on the posterior part, along with a timely transfer of torque and energy by tendons, explains the decrease in the duration of muscle activation towards the tail. The torque contribution from the body elasticity further clarifies the wave speed increase or the reverse of the wave direction of the muscle activation on the posterior part of a carangiform swimmer. For anguilliform swimmers, the absence of the aforementioned changes in the muscle activation on the posterior part is consistent with our torque prediction and the absence of long tendons from experimental observations. These results provide novel insights into the functions of muscles and tendons as an integral part of the internal driving system, especially from an energy perspective, and they highlight the differences in the internal driving systems between the two primary swimming modes.
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Peixes , Modelos Biológicos , Músculo Esquelético , Natação/fisiologia , Animais , Fenômenos Biomecânicos/fisiologia , Biologia Computacional , Simulação por Computador , Peixes/anatomia & histologia , Peixes/fisiologia , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/fisiologia , Fenômenos Fisiológicos MusculoesqueléticosRESUMO
Protein-peptide interactions are crucial in many cellular functions. Therefore, determining the structure of protein-peptide complexes is important for understanding the molecular mechanism of related biological processes and developing peptide drugs. HPEPDOCK is a novel web server for blind protein-peptide docking through a hierarchical algorithm. Instead of running lengthy simulations to refine peptide conformations, HPEPDOCK considers the peptide flexibility through an ensemble of peptide conformations generated by our MODPEP program. For blind global peptide docking, HPEPDOCK obtained a success rate of 33.3% in binding mode prediction on a benchmark of 57 unbound cases when the top 10 models were considered, compared to 21.1% for pepATTRACT server. HPEPDOCK also performed well in docking against homology models and obtained a success rate of 29.8% within top 10 predictions. For local peptide docking, HPEPDOCK achieved a high success rate of 72.6% on a benchmark of 62 unbound cases within top 10 predictions, compared to 45.2% for HADDOCK peptide protocol. Our HPEPDOCK server is computationally efficient and consumed an average of 29.8 mins for a global peptide docking job and 14.2 mins for a local peptide docking job. The HPEPDOCK web server is available at http://huanglab.phys.hust.edu.cn/hpepdock/.
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Algoritmos , Simulação de Acoplamento Molecular/métodos , Peptídeos/química , Proteínas/química , Software , Sequência de Aminoácidos , Benchmarking , Sítios de Ligação , Biologia Computacional/métodos , Bases de Dados de Proteínas , Humanos , Internet , Ligantes , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Mapeamento de Interação de Proteínas , Estrutura Secundária de Proteína , Homologia Estrutural de Proteína , Fatores de TempoRESUMO
BACKGROUND: Pediatric patients with genetic disorders have a higher incidence of pulmonary arterial hypertension (PAH) regardless of their heart defects. Filamin A (FLNA) mutation is recently recognized to be associated with pediatric pulmonary disorders, however, the clinical courses of PAH related to the mutation were reported in limited cases. Here, we presented a case and pooled data for better understanding of the correlation between FLNA mutation and pediatric PAH. CASE PRESENTATION: The patient was a 8-month-old female with repeated episodes of pneumonia. Physical examination revealed cleft lip, cleft palate and developmental retardation. Imaging examination showed a small atrial septal defect (ASD), central pulmonary artery enlargement, left upper lobe of lung atelectasis, and pulmonary infiltration. Genetic test showed she carried a de novo pathogenic variant of FLNA gene (c.5417-1G > A, p.-). Oral medications didn't slow the progression of PAH in the patient, and she died two years later. CONCLUSIONS: FLNA mutation causes rare but progressive PAH in addition to a wide spectrum of congenital heart disease and other comorbidities in pediatric patients. We highly recommend genetic testing for pediatric patients when suspected with PAH. Given the high mortality in this group, lung transplantation may offer a better outcome.
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Cardiopatias Congênitas , Hipertensão Pulmonar , Pneumopatias , Hipertensão Arterial Pulmonar , Criança , Feminino , Filaminas/genética , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/genética , LactenteRESUMO
In this paper, a signal-on electrochemiluminescence (ECL) cytosensing platform was developed based on nitrogen doped molybdenum oxynitride nanotube arrays (MoO xN y NTs) for the first time. The MoO xN y NTs exhibited excellent cathodic ECL behavior with 2-(dibutylamino)-ethanol (DBAE) as a coreactant. Owing to the surface plasmon resonance (SPR) of Au triggered by the ECL emission, the generation of "hot electrons" on AuNPs hampered DBAE to give off electrons and leads to the ECL quenching. This process could be hindered via adding "barriers" on the surface of AuNPs, such as antibody molecules and cells, to achieve the signal recovery. Based on the quenching-recovering mechanism, a facile label-free ECL cytosensor was constructed. The linear response of HepG2 cells was in the range of 50-13800 cells mL-1 with a low detection limit of 47 cells mL-1 (S/N = 3). Moreover, the proposed ECL cytosensor exhibits a satisfying performance in the practical application. Due to the anodic formation from a Mo metal substrate, the valuable feature is that the MoO xN y NTs-based ECL cytosensor can be used directly, thereby providing a stable and simplified ECL cytosensing platform for future clinical applications.
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Given the importance of peptide-mediated protein interactions in cellular processes, protein-peptide docking has received increasing attention. Here, we have developed a Hierarchical flexible Peptide Docking approach through fast generation and ensemble docking of peptide conformations, which is referred to as HPepDock. Tested on the LEADS-PEP benchmark data set of 53 diverse complexes with peptides of 3-12 residues, HPepDock performed significantly better than the 11 docking protocols of five small-molecule docking programs (DOCK, AutoDock, AutoDock Vina, Surflex, and GOLD) in predicting near-native binding conformations. HPepDock was also evaluated on the 19 bound/unbound and 10 unbound/unbound protein-peptide complexes of the Glide SP-PEP benchmark and showed an overall better performance than Glide SP-PEP+MM-GBSA and FlexPepDock in both bound and unbound docking. HPepDock is computationally efficient, and the average running time for docking a peptide is â¼15 min with the range from about 1 min for short peptides to around 40 min for long peptides.