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Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which current treatments are limited and drug development costs are prohibitive. Identifying drug targets for ASD is crucial for the development of targeted therapies. Summary-level data of expression quantitative trait loci obtained from GTEx, protein quantitative trait loci data from the ROSMAP project, and two ASD genome-wide association studies datasets were utilized for discovery and replication. We conducted a combined analysis using Mendelian randomization (MR), transcriptome-wide association studies, Bayesian colocalization, and summary-data-based MR to identify potential therapeutic targets associated with ASD and examine whether there are shared causal variants among them. Furthermore, pathway and drug enrichment analyses were performed to further explore the underlying mechanisms and summarize the current status of pharmacological targets for developing drugs to treat ASD. The protein-protein interaction (PPI) network and mouse knockout models were performed to estimate the effect of therapeutic targets. A total of 17 genes revealed causal associations with ASD and were identified as potential targets for ASD patients. Cathepsin B (CTSB) [odd ratio (OR) = 2.66 95, confidence interval (CI): 1.28-5.52, P = 8.84 × 10-3], gamma-aminobutyric acid type B receptor subunit 1 (GABBR1) (OR = 1.99, 95CI: 1.06-3.75, P = 3.24 × 10-2), and formin like 1 (FMNL1) (OR = 0.15, 95CI: 0.04-0.58, P = 5.59 × 10-3) were replicated in the proteome-wide MR analyses. In Drugbank, two potential therapeutic drugs, Acamprosate (GABBR1 inhibitor) and Bryostatin 1 (CASP8 inhibitor), were inferred as potential influencers of autism. Knockout mouse models suggested the involvement of the CASP8, GABBR1, and PLEKHM1 genes in neurological processes. Our findings suggest 17 candidate therapeutic targets for ASD and provide novel drug targets for therapy development and critical drug repurposing opportunities.
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Transtorno do Espectro Autista , Estudo de Associação Genômica Ampla , Proteômica , Humanos , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Animais , Camundongos , Transcriptoma , Locos de Características Quantitativas , Mapas de Interação de Proteínas/efeitos dos fármacos , Camundongos Knockout , Terapia de Alvo MolecularRESUMO
We report the first observation of the quantum Joule-Thomson (JT) effect in ideal and unitary Fermi gases. We study the temperature dynamics of these systems while they undergo an energy-per-particle conserving rarefaction. For scale-invariant systems, whose equations of state satisfy the relation UâPV, this rarefaction conserves the specific enthalpy, which makes it thermodynamically equivalent to a JT throttling process. We observe JT heating in an ideal Fermi gas, a direct consequence of Pauli blocking. In a unitary Fermi gas, we observe that the JT heating is marginal in the temperature range 0.2â²T/T_{F}â²0.8 as the repulsive quantum-statistical effect is lessened by the attractive interparticle interactions.
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Constructing uniform covalent organic framework (COF) film on substrates for electronic devices is highly desirable. Here, a simple and mild strategy is developed to prepare them by polymerization on a solid-liquid interface. The universality of the method is confirmed by the successful preparation of five COF films with different microstructures. These films have large lateral size, controllable thickness, and high crystalline quality. And COF patterns can also be directly achieved on substrates via hydrophilic and hydrophobic interface engineering, which is in favor of preparing device array. For application studies, the PyTTA-TPA (PyTTA: 4,4',4'',4'''-(1,3,6,8-Tetrakis(4-aminophenyl)pyrene and TPA: terephthalaldehyde) COF film has a high photoresponsivity of 59.79â µA W-1 at 420â nm for photoelectrochemical (PEC) detection. When employed as an active material for optoelectronic synaptic devices for the first attempt, it shows excellent light-stimulated synaptic plasticity properties such as short-term plasticity (STP), long-term plasticity (LTP), and the conversion of STP to LTP, which can be used to simulate biological synaptic functions.
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The manipulation of topological architectures in two-dimensional (2D) covalent organic framework (COF) materials for different applications is promising but remains a great challenge. Here, we first report the topology-selective synthesis of two distinct varieties of 2DCOFs, imine-based HT-COFs and benzimidazole-fused BI-HT-COFs, by simply altering acid catalysts. To HT-COFs, a superlattice of 1D channel with a persistent triangular shape is formed via Schiff base reaction, while to BI-HT-COFs, a hexagonal lattice structure with a highly conjugated structure and imidazole linkages is constructed due to an imine-based cyclization reaction. The two COFs exhibited marked differences in their bandgap, chemical stability, molecular adsorption, and catalytic activity, which make them have different fields of application. This work not only diversifies the hexaaminotriphenylene-based 2DCOF topologies but also provides vivid examples of structure-property relationships, which would facilitate fundamental research and potential applications of 2DCOFs.
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The offset linear canonical transform (OLCT) is an important research topic in many fields, and it has a more universal and elastic performance due to its extra parameters. However, although much work has been done concerning the OLCT, its fast algorithms are rarely addressed. In this paper, an O(N logâ¡N) fast OLCT (FOLCT) algorithm that can significantly reduce the amount of calculation and improve accuracy is proposed. First, the discrete form of the OLCT is provided, and several important properties of its kernel are advanced. Next, the FOLCT based on the fast Fourier transform (FT) is derived for its numerical implementation. Then, the numerical results indicate that the FOLCT is a serviceable tool for signal analysis; additionally, the FOLCT algorithm can be used for the FT, fractional FT, linear canonical transform, and other transforms. Finally, its application to the detection of linear frequency modulated signals and optical image encryption, which is a basic case in signal processing, is discussed. The FOLCT can be effectively applied for the fast numerical calculation of the OLCT with valid and accurate results.
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The composition of microbial communities varies in water and sediments, and changes in environmental factors have major effects on microbiomes. Here, we characterized variations in microbial communities and physicochemical factors at two sites in a large subtropical drinking water reservoir in southern China. The microbiomes of all sites, including the diversity and abundance of microbial species, were determined via metagenomics, and the relationships between microbiomes and physicochemical factors were determined via redundancy analysis. The dominant species in sediment and water samples differed; Dinobryon sp. LO226KS and Dinobryon divergens were dominant in sediment samples, whereas Candidatus Fonsibacter ubiquis and Microcystis elabens were dominant in water. The diversity was also significantly different in microbial alpha diversity between water and sediment habitats (p < 0.01). The trophic level index (TLI) was the major factor affecting the microbial community in water samples; Mycolicibacterium litorale and Mycolicibacterium phlei were significantly positively related to TLI. Furthermore, we also studied the distribution of algal toxin-encoding genes and antibiotic-resistant genes (ARGs) in the reservoir. It found that water samples contained more phycotoxin genes, with the cylindrospermopsin gene cluster most abundant. We found three genera highly related to cylindrospermopsin and explored a new cyanobacteria Aphanocapsa montana that may produce cylindrospermopsin based on the correlation through network analysis. The multidrug resistance gene was the most abundant ARG, while the relationship between ARGs and bacteria in sediment samples was more complicated than in water. The results of this study enhance our understanding of the effects of environmental factors on microbiomes. In conclusion, research on the properties, including profiles of algal toxin-encoding genes and ARGs, and microbial communities can aid water quality monitoring and conservation.
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Two-dimensional (2D) conjugated metal-organic framework (c-MOF) films bring a completely new opportunity in the fields of catalysis, energy, and sensors, but preparing large-area continuous 2D c-MOF films remains a tremendous challenge. Here, we report a universal recrystallization strategy to synthesize large-area continuous 2D c-MOF films, revealing that the recrystallization strategy can significantly improve the electrochemical sensor sensitivity. Applying the 2D Cu3(HHTP)2 (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) c-MOF film as the active layer, the electrochemical sensor for glucose detection shows a high sensitivity of 20600 µA mM-1 cm-2, which is the best compared with the active materials reported previously. Most importantly, the as-made Cu3(HHTP)2 c-MOF-based electrochemical sensor possesses excellent stability. Overall, this work brings a brand-new universal strategy to prepare large-area continuous 2D c-MOF films for electrochemical sensors.
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Organophosphorus flame retardants (OPFRs) are widely used in various industrial manufacturing processes; thus, their environmental impact in agglomerated industrial areas is of great concern. In this study, seventeen kinds of OPFRs and five kinds of organophosphate diesters (Di-OPs) in water and upper sediment samples from two urban rivers in the agglomerated industrial area of Shenzhen city, China, were investigated. The results showed that the total concentrations of detectable OPFRs ranged from 3438.83 to 12,838.87 ng/L with an average of 6494.94 ng/L in water samples and from 47.16 to 524.46 ng/g (dry weight, dw) with an average of 181.48 ng/g dw in sediment. The values were higher than those in other rivers worldwide. Tris(2-chloroethyl) phosphate (TCEP) is the predominant OPFRs in water and upper sediment, up to 10,664.23 ng/L in water and 414.12 ng/g dw in sediment. The total concentration of OPFRs of sediment samples in the Maozhou River was around twice as high as in the Guanlan River. The results indicated that the level of OPFRs was associated with the industrial activity intensity. Di-OPs exhibited lower concentrations than their parent compounds, and can be attributed to the degradation/metabolism of their parent compounds in the river. The sediment-water partition of OPFRs is significantly correlated with their log Kow values. Risk assessment revealed moderate ecological risks posed by OPFRs in water to aquatic organisms. The present study revealed the pollution status of OPFRs in rivers from agglomerated industrial and residential areas.
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Retardadores de Chama , Água , Compostos Organofosforados , Retardadores de Chama/análise , Rios , Organofosfatos , Monitoramento Ambiental/métodos , ChinaRESUMO
We report the creation and the study of the stability of a repulsive quasihomogeneous spin-1/2 Fermi gas with contact interactions. For the range of scattering lengths a explored, the dominant mechanism of decay is a universal three-body recombination toward a Feshbach bound state. We observe that the recombination coefficient K_{3}âε_{kin}a^{6}, where the first factor, the average kinetic energy per particle ε_{kin}, arises from a three-body threshold law, and the second one from the universality of recombination. Both scaling laws are consequences of Pauli blocking effects in three-body collisions involving two identical fermions. As a result of the interplay between Fermi statistics and the momentum dependence of the recombination process, the system exhibits nontrivial temperature dynamics during recombination, alternatively heating or cooling depending on its initial quantum degeneracy. The measurement of K_{3} provides an upper bound for the interaction strength achievable in equilibrium for a uniform repulsive Fermi gas.
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Conductive metal-organic frameworks (MOFs) have performed well in the fields of energy and catalysis, among which two-dimensional (2D) and three-dimensional (3D) MOFs are well-known. Here, we have synthesized a one-dimensional (1D) conductive metal-organic framework (MOF) in which hexacoordinated 1,5-Diamino-4,8-dihydroxy-9,10-anthraceneedione (DDA) ligands are connected by double Cu ions, resulting in nanoribbon layers with 1D π-d conjugated nanoribbon plane and out-of-plane π-π stacking, which facilitates charge transport along two dimensions. The DDA-Cu as a highly conductive n-type MOF has high crystalline quality with a conductivity of ~ 9.4 S·m-1, which is at least two orders of magnitude higher than that of conventional 1D MOFs. Its electrical band gap (Eg) and exciton binding energy (Eb) are approximately 0.49 eV and 0.3 eV, respectively. When utilized as electrode material in a supercapacitor, the DDA-Cu exhibits good charge storage capacity and cycle stability. Meanwhile, as thse active semiconductor layer, it successfully simulates the artificial visual perception system with excellent bending resistance and air stability as a MOF-based flexible optoelectronic synaptic case. The controllable preparation of high-quality 1D DDA-Cu MOF may enable new architectural designs and various applications in the future.
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Estruturas Metalorgânicas , Nanotubos de Carbono , Condutividade Elétrica , Catálise , EletrodosRESUMO
To investigate the molecular pathological mechanisms of irritable bowel syndrome with diarrhea (IBS-D) and elucidate the effects of acupuncture on IBS-D colonic mucosa protein abundance in rats, a label-free high-throughput liquid chromatography-tandem mass spectrometry (LC-MS)-based proteomics analysis was used to survey the global changes of colonic mucosa proteins between different groups. Sixteen Sprague-Dawley (SD) male rats were randomly divided into four groups: the control group (C); the IBS-D model group (M); the syndrome differentiation acupuncture group (SD) and the traditional acupuncture group (T). IBS-D model rats were obtained using the CAS (chronic acute combining stress model) method. Comparative bioinformatics analysis of the proteomic data was analyzed using MaxQuant software, Perseus software, online tools DAVID, VENNY and STRING. Functional enrichment and network analyses revealed a close relationship between IBS-D and several biological processes including energy metabolism, muscular excitation/contraction, and both traditional acupuncture and syndrome differentiation acupuncture can reverse the impairments of normal energy metabolism. Moreover, the syndrome differentiation acupuncture can regulate the protein cluster relating inflammation, wound repair and cell protection against oxidative stress which is associated with acupuncture analgesic effect. Differentially expressed proteins Atp5a1 and Bpnt1 were selected as representative proteins and subjected to western blotting. In conclusion, our study provides further insight into the pathological and molecular mechanisms of IBS-D and acupuncture treatments, and serves as an experimental basis for clinical applications.
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Terapia por Acupuntura , Síndrome do Intestino Irritável , Terapia por Acupuntura/métodos , Animais , Diarreia/complicações , Mucosa Intestinal/metabolismo , Síndrome do Intestino Irritável/complicações , Masculino , Proteínas/metabolismo , Proteômica , Ratos , Ratos Sprague-DawleyRESUMO
Allan-Herndon-Dudley syndrome (AHDS) is a very rare, X-linked psychomotor disability syndrome with delayed myelination, almost exclusively affecting boys. We present a case of a 4-year-old boy with AHDS who was found cyanotic, with intermittent vomiting and paroxysmal convulsions about 4 h after his parents went out, and was then taken to the hospital, where he eventually died the next day. The autopsy revealed foreign bodies in the tiny bronchi and alveoli of the deceased, congestion, and punctate hemorrhage in multiple organs, consistent with the diagnosis of asphyxia. Compared with a normally developing 4-year-old boy, the deceased showed cerebral atrophy and cerebral edema, and Luxol Fast Blue (LFB) stain indicated delayed cerebellar, hippocampal, and basal ganglia development and myelination. A novel frameshift mutation c.584delG in the SLC16A2 gene was detected. Family lineage investigation showed that the mutation was also detected in the deceased's 8-year-old brother and biological mother. The present work enriches the profile mutations in SLC16A2 related to AHDS and emphasizes the importance of autopsy and postmortem genetic analysis in such cases.
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Deficiência Intelectual Ligada ao Cromossomo X , Simportadores , Criança , Pré-Escolar , Mutação da Fase de Leitura , Humanos , Masculino , Deficiência Intelectual Ligada ao Cromossomo X/diagnóstico , Deficiência Intelectual Ligada ao Cromossomo X/genética , Transportadores de Ácidos Monocarboxílicos/genética , Hipotonia Muscular , Atrofia Muscular , Mutação , Simportadores/genéticaRESUMO
Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. Herein we report large-area -C=N- linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π-π stacking interactions with the aid of water and acetic acid. Wafer-scale 2D COF films with different structures have been successfully synthesized by adjusting their building blocks, suggesting its generic applicability. The carrier mobility of PyTTA-TPA COF films can reach 1.89 × 10-3 cm2 V-1 s-1. When employed as catalysts in hydrogen evolution reaction (HER), they show high electrocatalytic activity compared with metal-free COFs or even some metallic catalysts. Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π-conjugated systems.
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Human exposure to organophosphate esters (OPEs) is more pervasive in industrial areas manufacturing OPE-related products. OPE exposure is of great concern due to its associations with adverse health effects, while studies on OPE exposure in industrial districts are scarce. This study aimed to assess human exposure to OPEs in a typical industrial area producing large amounts of OPE-related products in Shenzhen, China. Tris (2-chloroethyl)-phosphate (TCEP), tris (2-chloroisopropyl) phosphate (TCPP) and other common OPEs were analyzed in urine (n = 30) and plasma (n = 21) samples. Moreover, we measured five OPE metabolites (mOPEs) in plasma samples (n = 21). The results show that TCPP and TCEP are dominant compounds, with moderate to high levels compared with those reported in urine and plasma samples from other regions. In addition, di-n-butyl phosphate (DnBP) and diethyl phosphite (DEP) were frequently detected in plasma samples and could be considered as biomarkers. Risk assessment revealed a moderate to high potential health risk from TCEP exposure. Our results provide basic data for human exposure to OPEs in industrial areas and call for the prevention and mitigation of industrial chlorinated OPE pollution.
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Retardadores de Chama , China , Ésteres , Humanos , Organofosfatos/urina , Fosfatos , PlastificantesRESUMO
Covalent organic frameworks (COFs) with well-defined supramolecular structures and high surface-area-to-volume ratio have received extensive attention on their adsorption of contaminants from micro- to nano-size. Here, we studied the adsorption mechanisms of three typical nanoplastics (NP), including polyethylene (PE), nylon-6 (PA 6), and polyethylene terephthalate (PET) on chemically stable COFs (TpPa-X, X = H, CH3, OH, NO2 and F) by molecular dynamics simulations. Depending on molecular structure and surface composition, two distinct interactions-electrostatic interaction and van der Waals (vdW) interaction-are identified to be responsible for the adsorption of different NP pollutants on TpPa-X. The vdW interaction is dominant during the adsorption process, while polar groups in polymers and COFs can enhance the adsorption because of the electrostatic interaction. Compared with other functional COFs, we found that TpPa-OH shows the strongest adsorption with the NP pollutants employed in this study. This work reveals the COF-polymer adsorption behavior and properties at atomic scale, which is crucial to the development of promising COF materials to deal with NP pollution.
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Facile synthesis and post-processing of covalent organic frameworks (COFs) under mild synthetic conditions are highly sought after and important for widespread utilizations in catalysis and energy storage. Here we report the synthesis of the chemically stable aza-fused COFs BPT-COF and PT-COF by a liquid-phase method. The process involves the spontaneous polycondensation of vicinal diamines and vicinal diketones, and is driven by the near-equilibrium growth of COF domains at a very low monomer concentration. The method permits inâ situ assembly of COFs and COF-GO hybrid materials and leads to the formation of a uniform conducting film on arbitrary substrates on vacuum filtration. When used as electrocatalysts, the as-prepared membranes show a fast hydrogen evolution reaction (HER) with a low overpotential (45â mV at 10â mA cm-2 ) and a small Tafel slope (53â mV dec-1 ), which are the best among metal-free catalysts. Our results may open a new route towards the preparation of highly π-conjugated COFs for multifunctional applications.
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2D metal-organic framework (MOF) film as the active layer show promising application prospects in various fields including sensors, catalysis, and electronic devices. However, exploring the application of 2D MOF film in the field of artificial synapses has not been implemented yet. In this work, we fabricated a novel 2D MOF film (Cu-THPP, THPP=5,10,15,20-Tetrakis(4-hydroxyphenyl)-21H,23H-porphine), and further used it as an active layer to explore the application in the simulation of human brain synapses. It shows excellent light-stimulated synaptic plasticity properties, and exhibits the foundation function of synapses such as long-term plasticity (LTP), short-term plasticity (STP), and the conversion of STP to LTP. Most critically, the MOF based artificial synaptic device exhibits an excellent stability in atmosphere. This work opens the door for the application of 2D MOF film in the simulation of human brain synapses.
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Materiais Biomiméticos/química , Membranas Artificiais , Estruturas Metalorgânicas/química , Materiais Biomiméticos/efeitos da radiação , Biomimética/métodos , Cobre/química , Cobre/efeitos da radiação , Luz , Estruturas Metalorgânicas/efeitos da radiação , Plasticidade Neuronal , Porfirinas/química , Porfirinas/efeitos da radiação , Sinapses/químicaRESUMO
The sensitive detection and identification of toxicants in oily matrices have suffered from difficulty in poisoning incidents, therefore it is necessary to develop the rapid and efficient analytical method to realize the on-site screening and analyzing. In this report, the surface-enhanced Raman spectroscopy (SERS) method was used to detect paraquat and diquat poisons in various oily matrix coupled with solvent extraction. The solvent extraction not only remove interfering impurities of oily substrates, but also can enrich and separate the poisons from oily matrix. It was demonstrated that the ethanol as the extractant was suitable for the rapid separation of poisons such as paraquat (PQ) and diquat (DQ) in oily matrix (soy sauce, pasta sauce, sesame oil, chili oil). Moreover, combined with a handheld Raman spectrometer, the entire detection process was completed within 8 min with the level of 10 ppb PQ and 100 ppb DQ. Furthermore, double-blind experiments verify the reliability of this method. The results demonstrate that this rapid and convenient method could be used for the effective enrichment and sensitive detection of poisons in several oily matrix and has the grate potential application in emergency response and public safety.
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Venenos , Análise Espectral Raman , Diquat , Etanol , Paraquat , Venenos/análise , Reprodutibilidade dos TestesRESUMO
The preparation of large-area 2D conductive metal-organic framework (MOF) films remains highly desirable but challenging. Here, inspired by the capillary phenomenon, a face-to-face confinement growth method to grow conductive 2D Cu2 (TCPP) (TCPP = meso-tetra(4-carboxyphenyl)porphine) MOF films on dielectric substrates is developed. Trace amounts of solutions containing low-concentration Cu2+ and TCPP are pumped cyclically into a micropore interface to produce this growth. The crystal structures are confirmed with various characterization techniques, which include high-resolution atomic force microscopy and cryogenic transmission electron microscopy (Cryo-TEM). The Cu2 (TCPP) MOF film exhibit an electrical conductivity of ≈0.007 S cm-1 , which is approximately four orders of magnitude higher than other carboxylic-acid-based MOF materials (10-6 S cm-1 ). Other wafer-scale conductive MOF films such as M3 (HHTP)2 (M = Cu, Co, and Ni; HHTP = 2,3,6,7,10,11-triphenylenehexol) can be produced utilizing this strategy and suggests this method has widescale applicability potential.