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1.
J Phys Chem Lett ; 15(31): 7939-7944, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39074357

RESUMO

We report chemical vapor deposition (CVD) synthesis of two quasi-one-dimensional (quasi-1D) polymorphs of BiSCl, denoted by y-BiSCl and r-BiSCl. The length of the CVD samples can reach about 0.4 mm. Such quasi-1D samples of the two polymorphs can be readily separated into individual pieces for either characterization or application. The two polymorphs can be clearly differentiated by Raman spectroscopy. First-principles calculations and group analysis are used to assign each Raman peak to the corresponding vibrational mode. Ultraviolet-visible measurements on solution grown thin-film samples reveal that the two polymorphs exhibit significantly different band gaps of 2.08 eV (y-BiSCl) and 1.81 eV (r-BiSCl). First-principles calculation further shows that the interatomic chain binding energy is 18.1 meV/Å2, confirming that the van der Waals stacking determines the difference in their band gaps. Our findings highlight the possibility of realizing the desired functionalities in quasi-1D materials by controlling stacking orientation.

2.
Front Neurol ; 15: 1344324, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872826

RESUMO

Objective: To construct radiomics models based on MRI at different time points for the early prediction of cystic brain radionecrosis (CBRN) for nasopharyngeal carcinoma (NPC). Methods: A total of 202 injured temporal lobes from 155 NPC patients with radiotherapy-induced temporal lobe injury (RTLI) after intensity modulated radiotherapy (IMRT) were included in the study. All the injured lobes were randomly divided into the training (n = 143) and validation (n = 59) sets. Radiomics models were constructed by using features extracted from T2WI at two different time points: at the end of IMRT (post-IMRT) and the first-detected RTLI (first-RTLI). A delta-radiomics feature was defined as the percentage change in a radiomics feature from post-IMRT to first-RTLI. The radiomics nomogram was constructed by combining clinical risk factors and radiomics signatures using multivariate logistic regression analysis. Predictive performance was evaluated using area under the curve (AUC) from receiver operating characteristic analysis and decision curve analysis (DCA). Results: The post-IMRT, first-RTLI, and delta-radiomics models yielded AUC values of 0.84 (95% CI: 0.76-0.92), 0.86 (95% CI: 0.78-0.94), and 0.77 (95% CI: 0.67-0.87), respectively. The nomogram exhibited the highest AUC of 0.91 (95% CI: 0.85-0.97) and sensitivity of 0.82 compared to any single radiomics model. From the DCA, the nomogram model provided more clinical benefit than the radiomics models or clinical model. Conclusion: The radiomics nomogram model combining clinical factors and radiomics signatures based on MRI at different time points after radiotherapy showed excellent prediction potential for CBRN in patients with NPC.

3.
Science ; 384(6698): eadh4265, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38781378

RESUMO

Nucleotide variants in cell type-specific gene regulatory elements in the human brain are risk factors for human disease. We measured chromatin accessibility in 1932 aliquots of sorted neurons and non-neurons from 616 human postmortem brains and identified 34,539 open chromatin regions with chromatin accessibility quantitative trait loci (caQTLs). Only 10.4% of caQTLs are shared between neurons and non-neurons, which supports cell type-specific genetic regulation of the brain regulome. Incorporating allele-specific chromatin accessibility improves statistical fine-mapping and refines molecular mechanisms that underlie disease risk. Using massively parallel reporter assays in induced excitatory neurons, we screened 19,893 brain QTLs and identified the functional impact of 476 regulatory variants. Combined, this comprehensive resource captures variation in the human brain regulome and provides insights into disease etiology.


Assuntos
Encefalopatias , Encéfalo , Cromatina , Regulação da Expressão Gênica , Elementos Reguladores de Transcrição , Humanos , Alelos , Encéfalo/metabolismo , Encefalopatias/genética , Cromatina/metabolismo , Neurônios/metabolismo , Locos de Características Quantitativas , Masculino , Feminino
4.
Virol J ; 21(1): 122, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816865

RESUMO

Hand, Foot and Mouth Disease (HFMD) is a highly contagious viral illness primarily affecting children globally. A significant epidemiological transition has been noted in mainland China, characterized by a substantial increase in HFMD cases caused by non-Enterovirus A71 (EV-A71) and non-Coxsackievirus A16 (CVA16) enteroviruses (EVs). Our study conducts a retrospective examination of 36,461 EV-positive specimens collected from Guangdong, China, from 2013 to 2021. Epidemiological trends suggest that, following 2013, Coxsackievirus A6 (CVA6) and Coxsackievirus A10 (CVA10) have emerged as the primary etiological agents for HFMD. In stark contrast, the incidence of EV-A71 has sharply declined, nearing extinction after 2018. Notably, cases of CVA10 infection were considerably younger, with a median age of 1.8 years, compared to 2.3 years for those with EV-A71 infections, possibly indicating accumulated EV-A71-specific herd immunity among young children. Through extensive genomic sequencing and analysis, we identified the N136D mutation in the 2 A protein, contributing to a predominant subcluster within genogroup C of CVA10 circulating in Guangdong since 2017. Additionally, a high frequency of recombination events was observed in genogroup F of CVA10, suggesting that the prevalence of this lineage might be underrecognized. The dynamic landscape of EV genotypes, along with their potential to cause outbreaks, underscores the need to broaden surveillance efforts to include a more diverse spectrum of EV genotypes. Moreover, given the shifting dominance of EV genotypes, it may be prudent to re-evaluate and optimize existing vaccination strategies, which are currently focused primarily target EV-A71.


Assuntos
Genoma Viral , Genótipo , Doença de Mão, Pé e Boca , Filogenia , China/epidemiologia , Humanos , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/virologia , Pré-Escolar , Lactente , Estudos Retrospectivos , Feminino , Masculino , Criança , Epidemiologia Molecular , Enterovirus/genética , Enterovirus/classificação , Enterovirus/isolamento & purificação , Enterovirus Humano A/genética , Enterovirus Humano A/isolamento & purificação , Genômica , Incidência , Adolescente , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/virologia
6.
Angew Chem Int Ed Engl ; 63(15): e202400582, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38308672

RESUMO

Large-scale deployment of proton exchange membranes water electrolysis (PEM-WE) requires a substantial reduction in usage of platinum group metals (PGMs) as indispensable electrocatalyst for cathodic hydrogen evolution reaction (HER). Ultra-fine PGMs nanocatalysts possess abundant catalytic sites at lower loading, but usually exhibit reduced stability in long-term operations under corrosive acidic environments. Here we report grafting the ultra-fine PtRu crystalline nanoalloys with PtxRuySez "amorphous skin" (c-PtRu@a-PtxRuySez) by in situ atomic layer selenation to simultaneously improve catalytic activity and stability. We found that the c-PtRu@a-PtxRuySez-1 with ~0.6 nm thickness amorphous skin achieved an ultra-high mass activity of 26.7 A mg-1 Pt+Ru at -0.07 V as well as a state-of-the-art durability maintained for at least 1000 h at -10 mA cm-2 and 550 h at -100 mA⋅cm-2 for acid HER. Experimental and theoretical investigations suggested that the amorphous skin not only improved the electrochemical accessibility of the catalyst surface and increasing the intrinsic activity of the catalytic sites, but also mitigated the dissolution/diffusion of the active species, thus resulting in improved catalytic activity and stability under acidic electrolyte. This work demonstrates a direction of designing ultra-fine PGMs electrocatalysts both with high utilization and robust durability, offers an in situ "amorphous skin" engineering strategy.

7.
Radiat Oncol ; 19(1): 9, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243277

RESUMO

BACKGROUND: Previous studies have demonstrated conflicting findings regarding the initial MRI patterns of radiotherapy-induced temporal lobe injury (RTLI) and the evolution of different RTLI patterns. The aim of this study was to evaluate the initial MRI pattern and evolution of RTLI in patients with nasopharyngeal carcinoma (NPC) by means of a large cohort study. METHODS: Data of patients with RTLI were retrospectively collected from two hospitals between January 2011 and December 2021. The injured lobes were categorized into three patterns based on initial MRI patterns: isolated white matter lesions (WMLs), isolated contrast-enhanced lesions (CELs), and combined WMLs and CELs. The latency period, MRI appearances, and temporal changes in WMLs and CELs were evaluated. RESULTS: A total of 913 RTLI patients with 1092 injured lobes were included in this study. The numbers of isolated WMLs, isolated CELs, and combined WMLs and CELs identified at the first MRI detection were 7 (0.6%), 172 (15.8%), and 913 (83.6%), respectively. The evolution of bilateral RTLI was different in the same patient, and that of unilateral RTLI combined with WMLs and CELs also may occur asynchronously. The time intervals from the initial MRI detection of isolated WMLs, isolated CELs, combined WMLs and CELs to the last negative MRI scan were 8.6, 8.9 and 11.0 months, respectively. A significant difference was observed in the time intervals between the three patterns (H = 14.287, P = 0.001). And the time interval was identified as an independent factor influencing the initial MRI pattern of RTLI after Poisson regression (P = 0.002). CONCLUSION: Both WMLs and CELs could be the initial and only MRI abnormalities in patients with RTLI. This study is of great significance in accurately diagnosing RTLI early and providing timely treatment options. Additionally, it provides clinical evidence for guidelines on NPC, emphasizing the importance of regular follow-up of NPC patients.


Assuntos
Neoplasias Nasofaríngeas , Lesões por Radiação , Humanos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/patologia , Estudos Retrospectivos , Estudos de Coortes , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/patologia , Lobo Temporal/patologia , Imageamento por Ressonância Magnética , Lesões por Radiação/patologia
8.
medRxiv ; 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38076956

RESUMO

Microglia, the innate immune cells of the central nervous system, have been genetically implicated in multiple neurodegenerative diseases. We previously mapped the genetic regulation of gene expression and mRNA splicing in human microglia, identifying several loci where common genetic variants in microglia-specific regulatory elements explain disease risk loci identified by GWAS. However, identifying genetic effects on splicing has been challenging due to the use of short sequencing reads to identify causal isoforms. Here we present the isoform-centric microglia genomic atlas (isoMiGA) which leverages the power of long-read RNA-seq to identify 35,879 novel microglia isoforms. We show that the novel microglia isoforms are involved in stimulation response and brain region specificity. We then quantified the expression of both known and novel isoforms in a multi-ethnic meta-analysis of 555 human microglia short-read RNA-seq samples from 391 donors, the largest to date, and found associations with genetic risk loci in Alzheimer's disease and Parkinson's disease. We nominate several loci that may act through complex changes in isoform and splice site usage.

9.
Front Immunol ; 14: 1257360, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37915583

RESUMO

The effectiveness of COVID-19 vaccines wanes over time and the emergence of the SARS-CoV-2 Omicron variant led to the accelerated expansion of efforts for booster vaccination. However, the effect and contribution of booster vaccination with inactivated COVID-19 vaccines remain to be evaluated. We conducted a retrospective close contacts cohort study to analyze the epidemiological characteristics and Omicron infection risk, and to evaluate the effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 infection, symptomatic COVID-19, and COVID-19 pneumonia during the outbreaks of Omicron BA.2 infection from 1 February to 31 July 2022 in Guangdong, China. A total of 46,547 close contacts were identified while 6.3% contracted Omicron BA.2 infection, 1.8% were asymptomatic infection, 4.1% developed mild COVID-19, and 0.3% had COVID-19 pneumonia. We found that females and individuals aged 0-17 or ≥ 60 years old were more prone to SARS-CoV-2 infection. The vaccinated individuals showed lower infection risk when compared with the unvaccinated people. The effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 was 28.6% (95% CI: 11.6%, 35.0%) and 39.6% (95% CI: 30.0, 47.9) among adults aged ≥ 18 years old, respectively when compared with full vaccination. Booster vaccination provided a moderate level of protection against SARS-CoV-2 infection (VE: 49.9%, 95% CI: 22.3%-67.7%) and symptomatic COVID-19 (VE: 62.6%, 95% CI: 36.2%-78.0%) among adults aged ≥ 60 years old. Moreover, the effectiveness of booster vaccination was 52.2% (95% CI: 21.3%, 70.9%) and 83.8% (95% CI: 28.1%, 96.3%) against COVID-19 pneumonia in adults aged ≥ 18 and ≥ 60 years old, respectively. The reduction of absolute risk rate of COVID-19 pneumonia in the booster vaccination group was 0·96% (95% CI: 0.33%, 1.11%), and the number needed to vaccinate to prevent one case of COVID-19 pneumonia was 104 (95% CI: 91, 303) in adults aged ≥ 60 years old. In summary, booster vaccination with inactivated COVID-19 vaccines provides a low level of protection against infection and symptomatic in adults of 18-59 years old, and a moderate level of protection in older adults of more than 60 years old, but a high level of protection against COVID-19 pneumonia in older adults.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos de Coortes , Estudos Retrospectivos , SARS-CoV-2 , China/epidemiologia
10.
Front Oncol ; 13: 1168995, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954080

RESUMO

Purpose: This study aims to develop and validate a model predictive for the incidence of grade 4 radiation-induced lymphopenia (G4RIL), based on dosiomics features and radiomics features from the planning CT of nasopharyngeal carcinoma (NPC) treated by radiation therapy. Methods: The dataset of 125 NPC patients treated with radiotherapy from August 2018 to March 2019 was randomly divided into two sets-an 85-sample training set and a 40-sample test set. Dosiomics features and radiomics features of the CT image within the skull bone and cervical vertebrae were extracted. A feature selection process of multiple steps was employed to identify the features that most accurately forecast the data and eliminate superfluous or insignificant ones. A support vector machine learning classifier with correction for imbalanced data was trained on the patient dataset for prediction of RIL (positive classifier for G4RIL, negative otherwise). The model's predictive capability was gauged by gauging its sensitivity (the likelihood of a positive test being administered to patients with G4RIL) and specificity in the test set. The area beneath the ROC curve (AUC) was utilized to explore the association of characteristics with the occurrence of G4RIL. Results: Three clinical features, three dosiomics features, and three radiomics features exhibited significant correlations with G4RIL. Those features were then used for model construction. The combination model, based on nine robust features, yielded the most impressive results with an ACC value of 0.88 in the test set, while the dosiomics model, with three dosiomics features, had an ACC value of 0.82, the radiomics model, with three radiomics features, had an ACC value of 0.82, and the clinical model, with its initial features, had an ACC value of 0.6 for prediction performance. Conclusion: The findings show that radiomics and dosiomics features are correlated with the G4RIL of NPC patients. The model incorporating radiomics features and dosiomics features from planning CT can predict the incidence of G4RIL in NPC patients.

11.
Front Psychol ; 14: 1167902, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711334

RESUMO

Introduction: Speech breathing is a term usually used to refer to the manner in which expired air and lung mechanics are utilized for the production of the airflow necessary for phonation. Neurologically, speech breathing overrides the normal rhythms of alveolar ventilation. Speech breathing is generated using the diaphragm, glottis, and tongue. The glottis is the opening between the vocal folds in the larynx; it is the primary valve between the lungs and the mouth, and by varying its degree of opening, the sound can be varied. The use of voice as an indicator of health has been widely reported. Chronic obstructive pulmonary disease (COPD) is the most common long-term respiratory disease. The main symptoms of COPD are increasing breathlessness, a persistent chesty cough with phlegm, frequent chest infections, and persistent wheezing. There is no cure for COPD, and it is one of the leading causes of death worldwide. The principal cause of COPD is tobacco smoking, and estimates indicate that COPD will become the third leading cause of death worldwide by 2030. The long-term aim of this research program is to understand how speech generation, breathing, and lung function are linked in people with chronic respiratory diseases such as COPD. Methods: This pilot study was designed to test an articulatory speech task that uses a single word ("helicopter"), repeated multiple times, to challenge speech-generated breathing and breathlessness. Specifically, a single-word articulation task was used to challenge respiratory system endurance in people with healthy lungs by asking participants to rapidly repeat the word "helicopter" for three 20-s runs interspersed with two 20-s rest periods of silent relaxed breathing. Acoustic and prosodic features were then extracted from the audio recordings of each adult participant. Results and discussion: The pause ratio increased from the first run to the third, representing an increasing demand for breath. These data show that the repeated articulation task challenges speech articulation in a quantifiable manner, which may prove useful in defining respiratory ill-health.

12.
Nat Genet ; 55(9): 1462-1470, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37550530

RESUMO

Binge eating disorder (BED) is the most common eating disorder, yet its genetic architecture remains largely unknown. Studying BED is challenging because it is often comorbid with obesity, a common and highly polygenic trait, and it is underdiagnosed in biobank data sets. To address this limitation, we apply a supervised machine-learning approach (using 822 cases of individuals diagnosed with BED) to estimate the probability of each individual having BED based on electronic medical records from the Million Veteran Program. We perform a genome-wide association study of individuals of African (n = 77,574) and European (n = 285,138) ancestry while controlling for body mass index to identify three independent loci near the HFE, MCHR2 and LRP11 genes and suggest APOE as a risk gene for BED. We identify shared heritability between BED and several neuropsychiatric traits, and implicate iron metabolism in the pathophysiology of BED. Overall, our findings provide insights into the genetics underlying BED and suggest directions for future translational research.


Assuntos
Transtorno da Compulsão Alimentar , Humanos , Transtorno da Compulsão Alimentar/genética , Transtorno da Compulsão Alimentar/psicologia , Estudo de Associação Genômica Ampla , Obesidade/genética , Fenótipo , Ferro
13.
J Colloid Interface Sci ; 651: 659-668, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37562307

RESUMO

In the context of industrialization and severe wastewater pollution, mercury ions pose a major threat due to their high toxicity. However, traditional adsorbents and common metal-organic framework (MOF) materials have limited effectiveness. This study focuses on combining magnetic materials with functionalized titanium-based MOF composite (SNN-MIL-125(Ti)@Fe3O4) to improve mercury ion adsorption. Through comprehensive characterization and analysis, the adsorption performance and mechanism of the material were studied. The optimal adsorption of the material was achieved at pH 5, exhibiting a pseudo-second-order adsorption model and the Hill theoretical capacity of 668.98 mg/g. Hill and Tempkin models confirmed the presence of chemical and physical adsorption sites on the material surface. Thermodynamic experiments showed a spontaneous endothermic process. Despite the presence of interfering ions, the material exhibited high selectivity for mercury ions. After four cycles, adsorption performance decreased by only 8%, indicating excellent reusability. Nitrogen- and sulfur-containing functional groups played a key role in mercury ion adsorption. In conclusion, SNN-MIL-125(Ti)@Fe3O4, as a magnetic MOF adsorption material, showed potential for effective remediation of mercury-contaminated wastewater. This study contributes to the development of efficient adsorption materials and enhances the understanding of their mechanism.

14.
Nat Med ; 29(7): 1832-1844, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37464041

RESUMO

Depression is a common psychiatric disorder and a leading cause of disability worldwide. Here we conducted a genome-wide association study meta-analysis of six datasets, including >1.3 million individuals (371,184 with depression) and identified 243 risk loci. Overall, 64 loci were new, including genes encoding glutamate and GABA receptors, which are targets for antidepressant drugs. Intersection with functional genomics data prioritized likely causal genes and revealed new enrichment of prenatal GABAergic neurons, astrocytes and oligodendrocyte lineages. We found depression to be highly polygenic, with ~11,700 variants explaining 90% of the single-nucleotide polymorphism heritability, estimating that >95% of risk variants for other psychiatric disorders (anxiety, schizophrenia, bipolar disorder and attention deficit hyperactivity disorder) were influencing depression risk when both concordant and discordant variants were considered, and nearly all depression risk variants influenced educational attainment. Additionally, depression genetic risk was associated with impaired complex cognition domains. We dissected the genetic and clinical heterogeneity, revealing distinct polygenic architectures across subgroups of depression and demonstrating significantly increased absolute risks for recurrence and psychiatric comorbidity among cases of depression with the highest polygenic burden, with considerable sex differences. The risks were up to 5- and 32-fold higher than cases with the lowest polygenic burden and the background population, respectively. These results deepen the understanding of the biology underlying depression, its disease progression and inform precision medicine approaches to treatment.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno Bipolar , Esquizofrenia , Masculino , Feminino , Humanos , Estudo de Associação Genômica Ampla , Depressão , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/genética , Esquizofrenia/epidemiologia , Esquizofrenia/genética , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Polimorfismo de Nucleotídeo Único/genética , Predisposição Genética para Doença
15.
Chem Soc Rev ; 52(17): 5968-6002, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37498342

RESUMO

Biomolecular electronics is a rapidly growing multidisciplinary field that combines biology, nanoscience, and engineering to bridge the two important fields of life sciences and molecular electronics. Proteins are remarkable for their ability to recognize molecules and transport electrons, making the integration of proteins into electronic devices a long sought-after goal and leading to the emergence of the field of protein-based bioelectronics, also known as proteotronics. This field seeks to design and create new biomolecular electronic platforms that allow for the understanding and manipulation of protein-mediated electronic charge transport and related functional applications. In recent decades, there have been numerous reports on protein-based bioelectronics using a variety of nano-gapped electrical devices and techniques at the single molecular level, which are not achievable with conventional ensemble approaches. This review focuses on recent advances in physical electron transport mechanisms, device fabrication methodologies, and various applications in protein-based bioelectronics. We discuss the most recent progress of the single or few protein-bridged electrical junction fabrication strategies, summarise the work on fundamental and functional applications of protein bioelectronics that enable high and dynamic electron transport, and highlight future perspectives and challenges that still need to be addressed. We believe that this specific review will stimulate the interdisciplinary research of topics related to protein-related bioelectronics, and open up new possibilities for single-molecule biophysics and biomedicine.


Assuntos
Eletrônica , Dispositivos Eletrônicos Vestíveis , Transporte de Elétrons , Nanotecnologia
16.
Small ; 19(35): e2300876, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37127875

RESUMO

The rational design of efficient and cost-effective electrocatalysts for oxygen evolution reaction (OER) with sluggish kinetics, is imperative to diverse clean energy technologies. The performance of electrocatalyst is usually governed by the number of active sites on the surface. Crystalline/amorphous heterostructure has exhibited unique properties and opens new paradigms toward designing electrocatalysts with abundant active sites for improved performance. Hence, Fe doped Ni-Co phosphite (Fe-NiCoHPi) electrocatalyst with cauliflower-like structure, comprising crystalline@amorphous core-shell nanorod, is reported. The experiments uncover that Fe is enriched in the amorphous shell due to the flexibility of the amorphous component. Further density functional theory calculations indicate that the strong electronic interaction between the enriched Fe in the amorphous shell and crystalline core host at the core-shell interface, leads to balanced binding energies of OER intermediates, which is the origin of the catalyst-activity. Eventually, the Fe-NiCoHPi exhibits remarkable activity, with low overpotentials of only 206 and 257 mV at current density of 15 and 100 mA cm-2 . Unceasing durability over 90 h is achieved, which is superior to the effective phosphate electrocatalysts. Although the applications at high current remain challenges , this work provides an approach for designing advanced OER electrocatalysts for sustainable energy devices.

17.
bioRxiv ; 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-37090548

RESUMO

Nucleotide variants in cell type-specific gene regulatory elements in the human brain are major risk factors of human disease. We measured chromatin accessibility in sorted neurons and glia from 1,932 samples of human postmortem brain and identified 34,539 open chromatin regions with chromatin accessibility quantitative trait loci (caQTL). Only 10.4% of caQTL are shared between neurons and glia, supporting the cell type specificity of genetic regulation of the brain regulome. Incorporating allele specific chromatin accessibility improves statistical fine-mapping and refines molecular mechanisms underlying disease risk. Using massively parallel reporter assays in induced excitatory neurons, we screened 19,893 brain QTLs, identifying the functional impact of 476 regulatory variants. Combined, this comprehensive resource captures variation in the human brain regulome and provides novel insights into brain disease etiology.

18.
Genetics ; 223(1)2023 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-36321965

RESUMO

Expression quantitative trait locus detection has become increasingly important for understanding how noncoding variants contribute to disease susceptibility and complex traits. The major challenges in expression quantitative trait locus fine-mapping and causal variant discovery relate to the impact of linkage disequilibrium on signals due to one or multiple functional variants that lie within a credible set. We perform expression quantitative trait locus fine-mapping using the all-but-one approach, conditioning each signal on all others detected in an interval, on the Consortium for the Architecture of Gene Expression cohorts of microarray-based peripheral blood gene expression in 2,138 European-ancestry human adults. We contrast these results with traditional forward stepwise conditional analysis and a Bayesian localization method. All-but-one conditioning significantly modifies effect-size estimates for 51% of 2,351 expression quantitative trait locus peaks, but only modestly affects credible set size and location. On the other hand, both conditioning approaches result in unexpectedly low overlap with Bayesian credible sets, with just 57% peak concordance and between 50% and 70% SNP sharing, leading us to caution against the assumption that any one localization method is superior to another. We also cross reference our results with ATAC-seq data, cell-type-specific expression quantitative trait locus, and activity-by-contact-enhancers, leading to the proposal of a 5-tier approach to further reduce credible set sizes and prioritize likely causal variants for all known inflammatory bowel disease risk loci active in immune cells.


Assuntos
Doenças Inflamatórias Intestinais , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Humanos , Teorema de Bayes , Mapeamento Cromossômico/métodos , Estudo de Associação Genômica Ampla/métodos , Desequilíbrio de Ligação , Doenças Inflamatórias Intestinais/genética
19.
J Eye Mov Res ; 16(4)2023.
Artigo em Inglês | MEDLINE | ID: mdl-38585238

RESUMO

The visual cues of lexical tones are more implicit and much less investigated than consonants and vowels, and it is still unclear what facial areas contribute to facial tones identification. This study investigated Chinese and English speakers' eye movements when they were asked to identify audiovisual Mandarin lexical tones. The Chinese and English speakers were presented with an audiovisual clip of Mandarin monosyllables (for instance, /a/, /à/, /i/, /ì/) and were asked to identify whether the syllables were a dipping tone (/a/, / i/) or a falling tone (/ à/, /ì/). These audiovisual syllables were presented in clear, noisy and silent (absence of audio signal) conditions. An eye-tracker recorded the participants' eye movements. Results showed that the participants gazed more at the mouth than the eyes. In addition, when acoustic conditions became adverse, both the Chinese and English speakers increased their gaze duration at the mouth rather than at the eyes. The findings suggested that the mouth is the primary area that listeners utilise in their perception of audiovisual lexical tones. The similar eye movements between the Chinese and English speakers imply that the mouth acts as a perceptual cue that provides articulatory information, as opposed to social and pragmatic information.

20.
Front Public Health ; 11: 1307321, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38348379

RESUMO

Background: The non-pharmaceutical interventions (NPIs) against COVID-19 may have affected the transmission of hand, foot and mouth disease (HFMD). We aimed to assess the impact of the NPIs on HFMD in the high epidemic area of HFMD, Guangdong Province. Methods: The data of HFMD cases, etiological information, and meteorological factors in Guangdong from January 1, 2012, to December 31, 2021, were collected. Using a Bayesian structural time series (BSTS) model integrated counterfactual framework, we assessed the effect of NPIs on HFMD by different intervention periods, populations (gender, age, occupation), and cities. We further explored the correlation between the reduction of HFMD and socioeconomic factors in 21 cities. Results: A total of 351,217 HFMD cases were reported and 455,327 cases were averted in Guangdong Province during 2020-2021 with a reduction of 84.94% (95%CI: 81.63-87.22%) in 2020 and 29.49% (95%CI: 15.26-39.54%) in 2021. The impact of NPIs on HFMD differed by age and gender. The effects of NPIs were more remarkable for children aged 0-2 years and scattered children. We found that the relative reductions in 21 cities were related to the composition ratio of children and COVID-19 incidence. Conclusion: The reduction of HFMD incidence was significantly associated with COVID-19 NPIs, and school closure was an effective intervention to prevent HFMD outbreaks. Our findings will contribute to the development of HFMD prevention and control measures.


Assuntos
COVID-19 , Doença de Mão, Pé e Boca , Criança , Humanos , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/prevenção & controle , Teorema de Bayes , COVID-19/epidemiologia , COVID-19/prevenção & controle , Incidência , China/epidemiologia
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