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1.
Proc Natl Acad Sci U S A ; 121(18): e2310283121, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38669183

RESUMO

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.


Assuntos
Proteínas de Transporte , Polaridade Celular , Proteínas de Membrana , Coluna Vertebral , Peixe-Zebra , Animais , Peixe-Zebra/genética , Peixe-Zebra/embriologia , Humanos , Camundongos , Polaridade Celular/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Coluna Vertebral/anormalidades , Coluna Vertebral/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Escoliose/genética , Escoliose/congênito , Escoliose/metabolismo , Via de Sinalização Wnt/genética , Predisposição Genética para Doença , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Feminino
2.
Brief Bioinform ; 25(4)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38980375

RESUMO

Structural variation (SV) is an important form of genomic variation that influences gene function and expression by altering the structure of the genome. Although long-read data have been proven to better characterize SVs, SVs detected from noisy long-read data still include a considerable portion of false-positive calls. To accurately detect SVs in long-read data, we present SVDF, a method that employs a learning-based noise filtering strategy and an SV signature-adaptive clustering algorithm, for effectively reducing the likelihood of false-positive events. Benchmarking results from multiple orthogonal experiments demonstrate that, across different sequencing platforms and depths, SVDF achieves higher calling accuracy for each sample compared to several existing general SV calling tools. We believe that, with its meticulous and sensitive SV detection capability, SVDF can bring new opportunities and advancements to cutting-edge genomic research.


Assuntos
Algoritmos , Humanos , Análise de Sequência de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Genômica/métodos , Variação Estrutural do Genoma , Software
3.
Proc Natl Acad Sci U S A ; 120(2): e2217493120, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36598938

RESUMO

In response to DNA damage, bacterial RecA protein forms filaments with the assistance of DinI protein. The RecA filaments stimulate the autocleavage of LexA, the repressor of more than 50 SOS genes, and activate the SOS response. During the late phase of SOS response, the RecA filaments stimulate the autocleavage of UmuD and λ repressor CI, leading to mutagenic repair and lytic cycle, respectively. Here, we determined the cryo-electron microscopy structures of Escherichia coli RecA filaments in complex with DinI, LexA, UmuD, and λCI by helical reconstruction. The structures reveal that LexA and UmuD dimers bind in the filament groove and cleave in an intramolecular and an intermolecular manner, respectively, while λCI binds deeply in the filament groove as a monomer. Despite their distinct folds and oligomeric states, all RecA filament binders recognize the same conserved protein features in the filament groove. The SOS response in bacteria can lead to mutagenesis and antimicrobial resistance, and our study paves the way for rational drug design targeting the bacterial SOS response.


Assuntos
Proteínas de Escherichia coli , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Resposta SOS em Genética , Microscopia Crioeletrônica , DNA Polimerase Dirigida por DNA/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Recombinases Rec A/metabolismo
4.
Cereb Cortex ; 34(5)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38741268

RESUMO

Anhedonia is a transdiagnostic symptom and associated with a spectrum of reward deficits among which the motivational dysfunction is poorly understood. Previous studies have established the abnormal cost-benefit trade-off as a contributor to motivational deficits in anhedonia and its relevant psychiatric diseases. However, it remains elusive how the anhedonic neural dynamics underlying reward processing are modulated by effort expenditure. Using an effort-based monetary incentive delay task, the current event-related potential study examined the neural dynamics underlying the effort-reward interplay in anhedonia using a nonclinical sample who scored high or low on an anhedonia questionnaire. We found that effort prospectively decreased reward effect on the contingent variation negativity and the target-P3 but retrospectively enhanced outcome effect on the feedback-P3 following effort expenditure. Compared to the low-anhedonia group, the high-anhedonia group displayed a diminished effort effect on the target-P3 during effort expenditure and an increased effort-enhancement effect for neutral trials during the feedback-P3 period following effort expenditure. Our findings suggest that anhedonia is associated with an inefficient control and motivation allocation along the efforted-based reward dynamics from effort preparation to effort production.


Assuntos
Anedonia , Motivação , Recompensa , Anedonia/fisiologia , Humanos , Masculino , Feminino , Adulto Jovem , Motivação/fisiologia , Eletroencefalografia , Adulto , Potenciais Evocados/fisiologia , Encéfalo/fisiologia , Adolescente
5.
Nucleic Acids Res ; 51(4): 1843-1858, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36688327

RESUMO

The discovery of new, active DNA transposons can expand the range of genetic tools and provide more options for genomic manipulation. In this study, a bioinformatics analysis suggested that Passer (PS) transposons, which are members of the pogo superfamily, show signs of recent and current activity in animals and may be active in some species. Cell-based transposition assays revealed that the native PS transposases from Gasterosteus aculeatus and Danio rerio displayed very high activity in human cells relative to the Sleeping Beauty transposon. A typical overproduction inhibition phenomenon was observed for PS, and transposition capacity was decreased by ∼12% with each kilobase increase in the insertion size. Furthermore, PS exhibited a pronounced integration preference for genes and their transcriptional regulatory regions. We further show that two domesticated human proteins derived from PS transposases have lost their transposition activity. Overall, PS may represent an alternative with a potentially efficient genetic manipulation tool for transgenesis and mutagenesis applications.


Assuntos
Elementos de DNA Transponíveis , Peixes , Técnicas Genéticas , Animais , Humanos , Peixes/genética , Técnicas de Transferência de Genes , Transposases/genética
6.
Proc Natl Acad Sci U S A ; 119(3)2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35012976

RESUMO

COVID-19 remains a stark health threat worldwide, in part because of minimal levels of targeted vaccination outside high-income countries and highly transmissible variants causing infection in vaccinated individuals. Decades of theoretical and experimental data suggest that nonspecific effects of non-COVID-19 vaccines may help bolster population immunological resilience to new pathogens. These routine vaccinations can stimulate heterologous cross-protective effects, which modulate nontargeted infections. For example, immunization with Bacillus Calmette-Guérin, inactivated influenza vaccine, oral polio vaccine, and other vaccines have been associated with some protection from SARS-CoV-2 infection and amelioration of COVID-19 disease. If heterologous vaccine interventions (HVIs) are to be seriously considered by policy makers as bridging or boosting interventions in pandemic settings to augment nonpharmaceutical interventions and specific vaccination efforts, evidence is needed to determine their optimal implementation. Using the COVID-19 International Modeling Consortium mathematical model, we show that logistically realistic HVIs with low (5 to 15%) effectiveness could have reduced COVID-19 cases, hospitalization, and mortality in the United States fall/winter 2020 wave. Similar to other mass drug administration campaigns (e.g., for malaria), HVI impact is highly dependent on both age targeting and intervention timing in relation to incidence, with maximal benefit accruing from implementation across the widest age cohort when the pandemic reproduction number is >1.0. Optimal HVI logistics therefore differ from optimal rollout parameters for specific COVID-19 immunizations. These results may be generalizable beyond COVID-19 and the US to indicate how even minimally effective heterologous immunization campaigns could reduce the burden of future viral pandemics.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Modelos Teóricos , SARS-CoV-2/imunologia , Estações do Ano , Vacinação/métodos , Algoritmos , Vacina BCG/administração & dosagem , Vacina BCG/imunologia , COVID-19/epidemiologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Pandemias/prevenção & controle , Admissão do Paciente/estatística & dados numéricos , SARS-CoV-2/fisiologia , Taxa de Sobrevida , Estados Unidos/epidemiologia , Vacinação/estatística & dados numéricos
7.
J Allergy Clin Immunol ; 153(4): 1125-1139, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38072195

RESUMO

BACKGROUND: Inborn errors of immunity (IEI) often lack specific disease models and personalized management. Signal transducer and activator of transcription (STAT)-1 gain of function (GoF) is such example of an IEI with diverse clinical phenotype with unclear pathomechanisms and unpredictable response to therapy. Limitations in obtaining fresh samples for functional testing and research further highlights the need for patient-specific ex vivo platforms. OBJECTIVE: Using STAT1-GoF as an example IEI, we investigated the potential of patient-derived expanded potential stem cells (EPSC) as an ex vivo platform for disease modeling and personalized treatment. METHODS: We generated EPSC derived from individual STAT1-GoF patients. STAT1 mutations were confirmed with Sanger sequencing. Functional testing including STAT1 phosphorylation/dephosphorylation and gene expression with or without Janus activating kinase inhibitors were performed. Functional tests were repeated on EPSC lines with GoF mutations repaired by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) editing. RESULTS: EPSC were successfully reprogrammed from STAT1-GoF patients and expressed the same pluripotent makers as controls, with distinct morphologic differences. Patient-derived EPSC recapitulated the functional abnormalities of index STAT1-GoF patients with STAT1 hyperphosphorylation and increased expression of STAT1 and its downstream genes (IRF1, APOL6, and OAS1) after IFN-γ stimulation. Addition of ruxolitinib and baricitinib inhibited STAT1 hyperactivation in STAT1-GoF EPSC in a dose-dependent manner, which was not observed with tofacitinib. Corrected STAT1 phosphorylation and downstream gene expression were observed among repaired STAT1-GoF EPSC cell lines. CONCLUSION: This proof-of-concept study demonstrates the potential of our patient-derived EPSC platform to model STAT1-GoF. We propose this platform when researching, recapitulating, and repairing other IEI in the future.


Assuntos
Mutação com Ganho de Função , Fator de Transcrição STAT1 , Células-Tronco , Humanos , Mutação , Fosforilação , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Células-Tronco/imunologia , Células-Tronco/metabolismo
8.
J Am Chem Soc ; 146(19): 13588-13597, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38695646

RESUMO

Membrane channel proteins (MCPs) play key roles in matter transport through cell membranes and act as major targets for vaccines and drugs. For emerging ionic liquid (IL) drugs, a rational understanding of how ILs affect the structure and transport function of MCP is crucial to their design. In this work, GPU-accelerated microsecond-long molecular dynamics simulations were employed to investigate the modulating mechanism of ILs on MCP. Interestingly, ILs prefer to insert into the lipid bilayer and channel of aquaporin-2 (AQP2) but adsorb on the entrance of voltage-gated sodium channels (Nav). Molecular trajectory and free energy analysis reflect that ILs have a minimal impact on the structure of MCPs but significantly influence MCP functions. It demonstrates that ILs can decrease the overall energy barrier for water through AQP2 by 1.88 kcal/mol, whereas that for Na+ through Nav is increased by 1.70 kcal/mol. Consequently, the permeation rates of water and Na+ can be enhanced and reduced by at least 1 order of magnitude, respectively. Furthermore, an abnormal IL gating mechanism was proposed by combining the hydrophobic nature of MCP and confined water/ion coordination effects. More importantly, we performed experiments to confirm the influence of ILs on AQP2 in human cells and found that treatment with ILs significantly accelerated the changes in cell volume in response to altered external osmotic pressure. Overall, these quantitative results will not only deepen the understanding of IL-cell interactions but may also shed light on the rational design of drugs and disease diagnosis.


Assuntos
Permeabilidade da Membrana Celular , Ativação do Canal Iônico , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Líquidos Iônicos/química , Líquidos Iônicos/metabolismo , Modelos Moleculares , Estrutura Terciária de Proteína , Água/química , Linhagem Celular
9.
J Am Chem Soc ; 146(1): 410-418, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38154093

RESUMO

Under the control of chiral ligand glutathione and in the presence of hexadecyltrimethylammonium bromide, Au deposition on Au seeds is known to give chiral nanostructures. We have previously shown that the protruding chiral patterns, as opposed to flat facets, are likely caused by active surface growth, where nonuniform ligand coverage could be responsible for the focused growth at a few active sites. By pushing the limit of such a growth mode, here, we use decahedral seeds to prepare homochiral nanopropellers with intricate patterns of deep valleys and protruding ridges. Control experiments show that the focused growth depends on the rates of Au deposition by changing either the seed concentration or the reductant concentration, consistent with the proposed mechanism. The dynamic growth competition between the ligand-deficient active sites and the ligand-rich surfaces gradually focuses the growth onto a few active sites, causing the expansion of grooves, squeezing of steep ridges, and a surprising 36° rotation of the pentagonal outline. The imbalanced deposition on the prochiral slopes is responsible for the tilted grooves, the twisted walls, and thus the well-separated and distorted blades, which become the origin of the chiroptical responses.

10.
J Gene Med ; 26(2): e3669, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38380717

RESUMO

BACKGROUND: This study investigated the role of the ferroptosis-related gene FTH1 in oral squamous cell carcinoma (OSCC) and evaluated the therapeutic potential of baicalin in OSCC cell treatment. METHODS: A prognostic model was established by bioinformatic analysis, consisting of 12 ferroptosis related genes (FRGs), and FTH1 was selected as the most significantly up-regulated FRGs. The clinical correlation of FTH1 in OSCC samples was evaluated by both immunohistochemical and bioinformatic characterizations. The effects of FTH1 on migration, invasion, epithelial-mesenchymal transition (EMT) and proliferation were determined by wound healing assays, transwell assays, western blotting and 5'-ethynl 2'-deoxyuridine proliferation assays, respectively. The effects of FTH1 on ferroptosis were tested via ferroptosis markers and Mito Tracker staining. In addition, the therapeutic effects of baicalin on OSCC cells were confirmed using EMT, migration, invasion, proliferation and ferroptosis assays. RESULTS: The 12 FRGs were predictive of the prognosis for OSCC patients, and FTH1 expression was identified as significantly up-regulated in OSCC samples, which was highly associated with survival, immune cell infiltration and drug sensitivity. Moreover, knocking down FTH1 inhibited cell proliferation, EMT and invasive phenotypes, but induced ferroptosis in OSCC cells (Cal27 and SCC25). Furthermore, baicalin directly suppressed expression of FTH1 in OSCC cells, and effectively promoted ferroptosis and inhibited the proliferation as well as EMT by directly targeting FTH1. CONCLUSIONS: This study has demonstrated that FTH1 is a therapeutic target for OSCC treatment, and has provided evidence that baicalin offers a promising alternative for OSCC treatment.


Assuntos
Carcinoma de Células Escamosas , Ferroptose , Flavonoides , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Ferroptose/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Movimento Celular , Ferritinas , Oxirredutases
11.
Small ; 20(13): e2308427, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37967321

RESUMO

Self-trapped excitons (STEs) typically give broadband photoluminescence emission with a large Stokes shift, which is important for the enhancement of the optical properties of materials. Here, low-dimensional La-doped BaTiO3 nanocrystals with defects are prepared using supercritical CO2 (SC CO2). The generation of the STEs is facilitated by doping La3+ ions and introducing CO2 pressure, which effectively enhance the luminescence intensity of BaTiO3. This discovery shows that the La ion doping concentration can modulate the photoluminescence of BaTiO3 nanocrystals under pressure. This work deepens the understanding of the influence of rare-earth-doped luminescent materials under pressure and provides insight to improve the capabilities of optical devices.

12.
Small ; 20(10): e2305641, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37914667

RESUMO

As a remarkable structure, 2D magnetic heterojunctions have attracted researchers' attention owing to their controlled manipulation in the electronic device. However, successful fabrication as well as modulation of their structure and compound remain challenging. Herein, a novel method is designed to obtain a CoCl2 /Co3 O4 heterojunction on Si/SiO2 substrate with the assistance of supercritical CO2 (SC CO2 ), and the as-fabricated sample has significantly increased coercivity and saturation magnetization, which is 11 times higher than pure Co3 O4 . Further, it can be found that the CO2 pressure has the decisive effect on the saturation magnetization of the sample. Therefore, it suggests that the tunable electronic-magnetic device can be anticipated to be obtained in the future.

13.
Small ; 20(16): e2308187, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38016073

RESUMO

Spintronic devices work by manipulating the spin of electrons other than charge transfer, which is of revolutionary significance and can largely reduce energy consumption in the future. Herein, ultrathin two-dimensional (2D) non-van der Waals (non-vdW) γ-Ga2O3 with room temperature ferromagnetism is successfully obtained by using supercritical CO2 (SC CO2). The stress effect of SC CO2 under different pressures selectively modulates the orientation and strength of covalent bonds, leading to the change of atomic structure including lattice expansion, introduction of O vacancy, and transition of Ga-O coordination (GaO4 and GaO6). Magnetic measurements show that pristine γ-Ga2O3 is nonferromagnetic, whereas the SC CO2 treated γ-Ga2O3 exhibits obvious ferromagnetic behavior with an optimal magnetization of 0.025 emu g-1 and a Curie temperature of 300 K.

14.
J Med Virol ; 96(1): e29380, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38235849

RESUMO

Hepatic venous pressure gradient (HVPG) is the gold standard for evaluating clinically significant portal hypertension (CSPH). However, reliable noninvasive methods are limited. Our study aims to investigate the diagnostic value of serum Golgi protein 73 (GP73) for CSPH in patients with compensated cirrhosis. The study enrolled 262 consecutive patients with compensated cirrhosis from three centers in China from February 2021 to September 2023, who underwent both serum GP73 tests and HVPG measurements. CSPH was defined as HVPG ≥ 10 mmHg. Diagnostic accuracy was evaluated using the areas under the receiver operating characteristic curve (AUC). The prevalence of CSPH was 56.9% (n = 149). There were significant differences between the CSPH and non-CSPH groups in the median serum GP73 level (126.8 vs. 73.1 ng/mL, p < 0.001). GP73 level showed a significant positive linear correlation with HVPG (r = 0.459, p < 0.001). The AUC for the diagnosis of CSPH using serum GP73 alone was 0.75 (95% confidence interval [CI] 0.68-0.81). Multivariate logistic regression analysis determined that the levels of GP73, platelets and international normalized ratio were independently associated with CSPH. The combination of these three markers was termed "IP73" score with an AUC value of 0.85 (95% CI 0.80-0.89) for CSPH. Using 0 as a cut-off value, the specificity and sensitivity of IP73 score were 77.9% and 81.9%, respectively. The IP73 score offers a novel, simple and noninvasive method of assessing CSPH in patients with compensated cirrhosis. A cut-off value of the IP73 score at 0 can distinguish patients with or without CSPH.


Assuntos
Técnicas de Imagem por Elasticidade , Hipertensão Portal , Humanos , Biomarcadores , Hipertensão Portal/complicações , Hipertensão Portal/diagnóstico , Fígado , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Curva ROC , Fatores de Tempo
15.
Opt Express ; 32(10): 16777-16789, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858875

RESUMO

Applications of the type-I fiber Bragg gratings (FBGs) written through the coating (TTC) in strain sensing and tunable distributed Bragg reflector (DBR) fiber lasers were demonstrated. We reported the principle of selecting the distance between the fiber and the phase mask when writing type-I TTC FBGs. Type-I TTC FBGs written in commercially available acrylate-coated fibers with various geometries and their strain responses were demonstrated. Results showed that the strain sensitivity of FBGs increases as the core-diameter decreases, probably due to the waveguide effect. In addition, a continuously tunable DBR fiber laser based on TTC FBGs was achieved with a wavelength tuning range of 19.934 nm around 1080 nm, by applying a strain of 0-21265.8 µÉ› to the laser resonant cavity. The wavelength tuning range was limited by the splice point between the gain fiber and the passive fiber for transmitting pump and signal lasers. When the pump power was 100 mW, the relative intensity noises were -97.334 dB/Hz at the relaxation oscillation peak of 880 kHz and -128 dB/Hz at frequencies greater than 3 MHz. The results open a potential scheme to design and implement continuously tunable fiber lasers and fiber laser sensors for strain sensing with a higher resolution.

16.
Mol Psychiatry ; 28(11): 4853-4866, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37737484

RESUMO

Exposure to preadult environmental exposures may have long-lasting effects on mental health by affecting the maturation of the brain and personality, two traits that interact throughout the developmental process. However, environment-brain-personality covariation patterns and their mediation relationships remain unclear. In 4297 healthy participants (aged 18-30 years), we combined sparse multiple canonical correlation analysis with independent component analysis to identify the three-way covariation patterns of 59 preadult environmental exposures, 760 adult brain imaging phenotypes, and five personality traits, and found two robust environment-brain-personality covariation models with sex specificity. One model linked greater stress and less support to weaker functional connectivity and activity in the default mode network, stronger activity in subcortical nuclei, greater thickness and volume in the occipital, parietal and temporal cortices, and lower agreeableness, consciousness and extraversion as well as higher neuroticism. The other model linked higher urbanicity and better socioeconomic status to stronger functional connectivity and activity in the sensorimotor network, smaller volume and surface area and weaker functional connectivity and activity in the medial prefrontal cortex, lower white matter integrity, and higher openness to experience. We also conducted mediation analyses to explore the potential bidirectional mediation relationships between adult brain imaging phenotypes and personality traits with the influence of preadult environmental exposures and found both environment-brain-personality and environment-personality-brain pathways. We finally performed moderated mediation analyses to test the potential interactions between macro- and microenvironmental exposures and found that one category of exposure moderated the mediation pathways of another category of exposure. These results improve our understanding of the effects of preadult environmental exposures on the adult brain and personality traits and may facilitate the design of targeted interventions to improve mental health by reducing the impact of adverse environmental exposures.


Assuntos
Encéfalo , Personalidade , Adulto , Humanos , Neuroticismo , Mapeamento Encefálico , Exposição Ambiental
17.
Langmuir ; 40(24): 12553-12564, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38829289

RESUMO

In this study, dopamine-modified graphene aerogel (DGA) is synthesized through a one-step hydrothermal method using graphene oxide as the precursor and dopamine as the reducing agent. Subsequently, in situ immersion synthesis is conducted to obtain ZIF-8 loaded on a dopamine-modified graphene aerogel skeleton (ZDGA), featuring a regular honeycomb interconnected mesoporosity and a high specific surface area of 532.8 m2/g. The synthesized ZDGA exhibited exceptional adsorption performance for the cationic dye malachite green. At room temperature, ZDGA achieved an impressive equilibrium adsorption capacity of 6578.34 mg/g. The adsorption process followed pseudo-secondary kinetics and adhered to the Langmuir model, indicating chemically dominated adsorption on a monomolecular layer. Intraparticle diffusion was the primary rate determinant, with π-π stacking, electrostatic adsorption, hydrogen bonding, and Lewis acid-base interactions serving as the key driving forces. It has an ideal specific surface area and good cycling performance, which highlights its potential application in dye wastewater treatment.

18.
PLoS Comput Biol ; 19(3): e1011021, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37000844

RESUMO

Although some methods for estimating the instantaneous reproductive number during epidemics have been developed, the existing frameworks usually require information on the distribution of the serial interval and/or additional contact tracing data. However, in the case of outbreaks of emerging infectious diseases with an unknown natural history or undetermined characteristics, the serial interval and/or contact tracing data are often not available, resulting in inaccurate estimates for this quantity. In the present study, a new framework was specifically designed for joint estimates of the instantaneous reproductive number and serial interval. Concretely, a likelihood function for the two quantities was first introduced. Then, the instantaneous reproductive number and the serial interval were modeled parametrically as a function of time using the interpolation method and a known traditional distribution, respectively. Using the Bayesian information criterion and the Markov Chain Monte Carlo method, we ultimately obtained their estimates and distribution. The simulation study revealed that our estimates of the two quantities were consistent with the ground truth. Seven data sets of historical epidemics were considered and further verified the robust performance of our method. Therefore, to some extent, even if we know only the daily incidence, our method can accurately estimate the instantaneous reproductive number and serial interval to provide crucial information for policymakers to design appropriate prevention and control interventions during epidemics.


Assuntos
Epidemias , Teorema de Bayes , Surtos de Doenças , Simulação por Computador , Funções Verossimilhança
19.
Eur Radiol ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38491129

RESUMO

OBJECTIVES: To explore the value of the synthetic MRI (SyMRI), combined with amide proton transfer-weighted (APTw) MRI for quantitative and morphologic assessment of sinonasal lesions, which could provide relative scale for the quantitative assessment of tissue properties. METHODS: A total of 80 patients (31 malignant and 49 benign) with sinonasal lesions, who underwent the SyMRI and APTw examination, were retrospectively analyzed. Quantitative parameters (T1, T2, proton density (PD)) and APT % were obtained through outlining the region of interest (ROI) and comparing the two groups utilizing independent Student t test or a Wilcoxon test. Receiver operating characteristic curve (ROC), Delong test, and logistic regression analysis were performed to assess the diagnostic efficiency of one-parameter and multiparametric models. RESULTS: SyMRI-derived mean T1, T2, and PD were significantly higher and APT % was relatively lower in benign compared to malignant sinonasal lesions (p < 0.05). The ROC analysis showed that the AUCs of the SyMRI-derived quantitative (T1, T2, PD) values and APT % ranged from 0.677 to 0.781 for differential diagnosis between benign and malignant sinonasal lesions. The T2 values showed the best diagnostic performance among all single parameters for differentiating these two masses. The AUCs of combined SyMRI-derived multiple parameters with APT % (AUC = 0.866) were the highest than that of any single parameter, which was significantly improved (p < 0.05). CONCLUSION: The combination of SyMRI and APTw imaging has the potential to reflect intrinsic tissue characteristics useful for differentiating benign from malignant sinonasal lesions. CLINICAL RELEVANCE STATEMENT: Combining synthetic MRI with amide proton transfer-weighted imaging could function as a quantitative and contrast-free approach, significantly enhancing the differentiation of benign and malignant sinonasal lesions and overcoming the limitations associated with the superficial nature of endoscopic nasal sampling. KEY POINTS: • Synthetic MRI and amide proton transfer-weighted MRI could differentiate benign from malignant sinonasal lesions based on quantitative parameters. • The diagnostic efficiency could be significantly improved through synthetic MRI + amide proton transfer-weighted imaging. • The combination of synthetic MRI and amide proton transfer-weighted MRI is a noninvasive method to evaluate sinonasal lesions.

20.
Inorg Chem ; 63(19): 8750-8763, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38693869

RESUMO

Using a quinoline substituted Qsal ligand, Hqsal-5-Brq (Hqsal-5-Brq = N-(5-bromo-8-quinolyl)salicylaldimine), four FeIII complexes, [Fe(qsal-5-Brq)2]A·CH3OH (Y = NO3- (1NO3), BF4- (2BF4), PF6- (3PF6), OTf- (4OTf), were prepared and characterized. Structure analysis revealed that complex 2BF4 contained two species (2BF4(P1̅) and 2BF4(C2/c)). In these compounds except 3PF6, the [Fe(qsal-5-Brq)2]+ cations form 1D chains through π-π interactions and other weak interactions. Adjacent chains are connected to form the 2D "Chain Layer" structures and 3D structures through various supramolecular interactions. For 3PF6, a "Dimer Chain" structure is formed from the loosely connected dimers. Magnetic studies revealed that compounds 1NO3 and 2BF4(P1̅) displayed abrupt hysteretic SCO with the transition temperature T1/2↓ = 235 K, T1/2↑ = 240 K for 1NO3 and T1/2↓ = 230 K, T1/2↑ = 235 K for 2BF4(P1̅), while compounds 3PF6 and 4OTf are in the HS state. Desolvation of the complexes significantly modifies their SCO properties: the desolvated 1NO3 and 2BF4 show a gradual SCO, desolvated 3PF6 undergoes a two-step SCO, and desolvated 4OTf exhibits a hysteretic transition. Overall, this work reported the FeIII-SCO complexes of the quinoline-substituted Hqsal ligand and highlighted the potential of these ligands for the development of interesting FeIII-SCO materials.

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