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1.
Cell ; 183(2): 490-502.e18, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33002410

RESUMO

The non-receptor protein tyrosine phosphatase (PTP) SHP2, encoded by PTPN11, plays an essential role in RAS-mitogen-activated protein kinase (MAPK) signaling during normal development. It has been perplexing as to why both enzymatically activating and inactivating mutations in PTPN11 result in human developmental disorders with overlapping clinical manifestations. Here, we uncover a common liquid-liquid phase separation (LLPS) behavior shared by these disease-associated SHP2 mutants. SHP2 LLPS is mediated by the conserved well-folded PTP domain through multivalent electrostatic interactions and regulated by an intrinsic autoinhibitory mechanism through conformational changes. SHP2 allosteric inhibitors can attenuate LLPS of SHP2 mutants, which boosts SHP2 PTP activity. Moreover, disease-associated SHP2 mutants can recruit and activate wild-type (WT) SHP2 in LLPS to promote MAPK activation. These results not only suggest that LLPS serves as a gain-of-function mechanism involved in the pathogenesis of SHP2-associated human diseases but also provide evidence that PTP may be regulated by LLPS that can be therapeutically targeted.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33048737

RESUMO

Most visual analytics systems assume that all foraging for data happens before the analytics process; once analysis begins, the set of data attributes considered is fixed. Such separation of data construction from analysis precludes iteration that can enable foraging informed by the needs that arise in-situ during the analysis. The separation of the foraging loop from the data analysis tasks can limit the pace and scope of analysis. In this paper, we present CAVA, a system that integrates data curation and data augmentation with the traditional data exploration and analysis tasks, enabling information foraging in-situ during analysis. Identifying attributes to add to the dataset is difficult because it requires human knowledge to determine which available attributes will be helpful for the ensuing analytical tasks. CAVA crawls knowledge graphs to provide users with a a broad set of attributes drawn from external data to choose from. Users can then specify complex operations on knowledge graphs to construct additional attributes. CAVA shows how visual analytics can help users forage for attributes by letting users visually explore the set of available data, and by serving as an interface for query construction. It also provides visualizations of the knowledge graph itself to help users understand complex joins such as multi-hop aggregations. We assess the ability of our system to enable users to perform complex data combinations without programming in a user study over two datasets. We then demonstrate the generalizability of CAVA through two additional usage scenarios. The results of the evaluation confirm that CAVA is effective in helping the user perform data foraging that leads to improved analysis outcomes, and offer evidence in support of integrating data augmentation as a part of the visual analytics pipeline.

3.
Int J Biol Macromol ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33045296

RESUMO

The widespread use of nanomaterials poses a great threat to human living environments. Among them, biomass-derived cellulose nanoparticle (CN) is one of the widely used nanomaterials. To date, the toxicity of CNs during embryonic development remains undetermined. In this study, we exposed zebrafish embryos to cellulose nanofibrils (CNFs) and cellulose nanocrystals (CNCs) to evaluate the toxicity of these CNs. Exposure to CNFs or CNCs below 30 mg/ml exhibited no dose-dependent increases in malformation and mortality in zebrafish embryos. Then we demonstrated that CNs were highly enriched in zebrafish embryo via imaging analyses of embryos treated with FITC-coupled CNCs. In addition, we found that CNF or CNC exposure resulted in compromised motor ability of zebrafish larva. Furthermore, it was revealed that the differentiation and the morphogenesis of motor neurons were significantly interrupted. While, blood vessels were normally patterned, suggesting the specific neurotoxicity of these nanomaterials. Transcriptome sequencing assay showed that the neurotoxicity of CNs in the motor neurons might be attributed to the expression alteration of neural genes. In summary, we discovered the neurotoxicity of CNs for the first time.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33017504

RESUMO

Lithium oxygen (Li-O 2 ) batteries have attracted extensive research interest due to their high energy density. Other than Li 2 O 2 (a typical discharge product in Li-O 2 batteries), LiOH is proved to be electrochemically active as an alternative product. Here we report a simple strategy to achieve a reversible LiOH based Li-O 2 battery with the use of a cation additive, sodium ions, to the lithium electrolyte. Without redox mediators in the cell, LiOH is detected as the sole discharge product and it charges at a low charge potential of 3.4 V. A solution-based reaction route is proposed, showing that the competing solvation environment of the catalyst and Li + leads to LiOH precipitation at the cathode. It is critical to tune the cell chemistry of Li-O 2 batteries by designing a simple system to promote LiOH formation/decomposition.

5.
Adv Mater ; : e2005531, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002239

RESUMO

Smart and wearable electronics have aroused substantial demand for flexible portable power sources, but it remains a large challenge to realize scalable production of wearable batteries/supercapacitors with high electrochemical performance and remarkable flexibility simultaneously. Here, a scalable approach is developed to prepare wearable solid-state lithium-ion capacitors (LICs) with superior performance enabled by synergetic engineering from materials to device architecture. Nitrogen-doped hierarchical carbon (HC) composed of 1D carbon nanofibers welded with 2D carbon nanosheets is synthesized via a unique self-propagating high-temperature synthesis (SHS) technique, which exhibits superior electrochemical performance. Subsequently, inspired by origami, here, wave-shaped LIC punch-cells based on the above materials are designed by employing a compatible and scalable post-imprint technology. Finite elemental analysis (FEA) confirms that the bending stress of the punch-cell can be offset effectively, benefiting from the wave architecture. The wearable solid-state LIC punch-cell exhibits large energy density, long cyclic stability, and superior flexibility. This study demonstrates great promise for scalable fabrication of wearable energy-storage systems.

6.
Appl Opt ; 59(24): 7448-7454, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32902513

RESUMO

In this paper, we experimentally demonstrate an approach that "hides" a low-intensity 50 Gbit/s quadrature-phase-keying (QPSK) free-space optical beam when it coaxially propagates on the same wavelength with an orthogonal high-intensity 50 Gbit/s QPSK optical beam. Our approach is to coaxially transmit the strong and weak beams carrying different orthogonal spatial modes within a modal basis set, e.g., orbital angular momentum (OAM) modes. Although the weak beam has much lower power than that of the strong beam, and the beams are in the same frequency band and on the same polarization, the two beams can still be effectively demultiplexed with little inherent crosstalk at the intended receiver due to their spatial orthogonality. However, an eavesdropper may not readily identify the weak beam when simply analyzing the spatial intensity profile. The correlation coefficient between the intensity profiles of the strong beam and the combined strong and weak beams is measured to characterize the potential for "hiding" a weak beam when measuring intensity profiles. Such a correlation coefficient is demonstrated to be higher than 0.997 when the power difference between the strong fundamental Gaussian beam and the weak OAM beam is ∼8,∼10, and ∼10dB for the weak OAM -1,-2, and -3 beams, respectively. Moreover, a 50 Gbit/s QPSK data link having its Q factor above the 7% forward error correction limit is realized when the power of the weak OAM -3 beam is 30 dB lower than that of the strong fundamental Gaussian beam.

7.
Langmuir ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32940475

RESUMO

The interfacial region between nanoparticles and polymer matrix plays a critical role in influencing the mechanical behavior of polymer nanocomposites. In this work, a set of model systems based on poly(methyl methacrylate) (PMMA) matrix containing poly(alkyl glycidyl ether) brushes grafted on 50 nm metal-organic-framework (MOF) nanoparticles were synthesized and investigated. By systematically increasing the polymer brush length and graft density on the MOF nanoparticles, the fracture behavior of PMMA/MOF nanocomposite changes from forming only a few large crazes to generating massive crazing and to undergoing shear banding, which results in significant improvement in fracture toughness. The implication of the present finding for the interfacial design of the nanoparticles for the development of high-performance, multifunctional polymer nanocomposites is discussed.

8.
J Chem Theory Comput ; 16(10): 6377-6382, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-32910647

RESUMO

Predicting the poses of small-molecule ligands in protein binding sites is often done by virtual screening algorithms such as DOCK. In principle, molecular dynamics (MD) using atomistic force fields could give better free-energy-based pose selection, but MD is computationally expensive. Here, we ask if modeling employing limited data (MELD)-accelerated MD (MELD × MD) can pick out the best DOCK poses taken as input. We study 30 different ligand-protein pairs. MELD × MD finds native poses, based on best free energies, in 23 out of the 30 cases, 20 of which were previously known DOCK failures. We conclude that MELD × MD can add value for predicting accurate poses of small molecules bound to proteins.

9.
Ecotoxicol Environ Saf ; 207: 111271, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32920314

RESUMO

Antimony has been listed as a critical pollutant in many countries because of its toxic effects on earth organisms. In this study, titanate nanosheets (TNS) were prepared with a high specific surface area by alkaline hydrothermal method. The adsorption mechanism and adsorption capacity of removing Sb(III) from aqueous solutions with TNS as an adsorbent were investigated for the first time. The FTIR and XPS analysis indicated that the interlayer sodium ions of TNS were responsible for Sb(III) adsorption. The batch experiments were conducted on solution pH, adsorbent dosage, initial concentration and reaction time. The results exhibited that when pH was 2, the removal rate was about 90% with the dosage of TNS was 0.1 g/L. The adsorption reaction was exceedingly rapid in the initial 5 min, and then the reaction was in equilibrium after about 30 min. The experimental data were better fitted with Langmuir isotherm model, and the maximum adsorption amount could attain 232.56 mg/g. The experiments showed that TNS had outstanding anti-interference performance to common cations. Therefore, TNS were considered to be an excellent material for removing Sb(III) from aqueous solutions.

10.
Water Res ; 186: 116388, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32916623

RESUMO

Understanding where nitrate is mobilized from and under what conditions is required to reduce nitrate loss and protect water quality. Low frequency sampling may inadequately capture hydrological and biogeochemical processes that will influence nitrate behavior. We used high-frequency isotope sampling and in-situ nitrate sensing to explore nitrate export and transformation in a karst critical zone. Nitrate was mobilised during light rainfall, and transferred from soil layers to the karst matrix, where some nitrate was retained and denitrified. Nitrate isotopic composition changed rapidly during the rising limb of events and slowly during the falling limb. The main nitrate source was synthetic fertiliser (up to 80% during event flow), transported by conduit flow following high rainfall events, and this contribution increased significantly as discharge increased. Soil organic nitrogen contribution remained constant indicating at baseflow this is the primary source. Isotope source appointment of nitrate export revealed that synthetic fertilizer accounted for more than half of the total nitrate export, which is double that of the secondary source (soil organic nitrogen), providing valuable information to inform catchment management to reduce nitrate losses and fluvial loading. Careful land management and fertilizer use are necessary to avoid nitrate pollution in the karst agroecosystem, for example by timing fertilizer applications to allow for plant uptake of nitrate before rainfall can flush it from the soils into the karst and ultimately into catchment drainage.

11.
JCI Insight ; 5(17)2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32879140

RESUMO

More than 90% of autoimmune-associated variants are located in noncoding regions, leading to challenges in deciphering the underlying causal roles of functional variants and genes and biological mechanisms. Therefore, to reduce the gap between traditional genetic findings and mechanistic understanding of disease etiologies and clinical drug development, it is important to translate systematically the regulatory mechanisms underlying noncoding variants. Here, we prioritized functional noncoding SNPs with regulatory gene targets associated with 19 autoimmune diseases by incorporating hundreds of immune cell-specific multiomics data. The prioritized SNPs are associated with transcription factor (TF) binding, histone modification, or chromatin accessibility, indicating their allele-specific regulatory roles. Their target genes are significantly enriched in immunologically related pathways and other known immunologically related functions. We found that 90.1% of target genes are regulated by distal SNPs involving several TFs (e.g., the DNA-binding protein CCCTC-binding factor [CTCF]), suggesting the importance of long-range chromatin interaction in autoimmune diseases. Moreover, we predicted potential drug targets for autoimmune diseases, including 2 genes (NFKB1 and SH2B3) with known drug indications on other diseases, highlighting their potential drug repurposing opportunities. Taken together, these findings may provide useful information for future experimental follow-up and drug applications on autoimmune diseases.

12.
Poult Sci ; 99(10): 5118-5126, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988550

RESUMO

Multidrug-resistant (MDR) Escherichia coli are responsible for difficult-to-treat infections. We sought to determine the prevalence and characteristics of MDR E. coli strains isolated from poultry and clinical patients in the same geographical region. Eighty-seven E. coli strains were isolated from poultry with perihepatitis lesions at different slaughterhouses, and 356 nonrepetitive E. coli strains were isolated from clinical patients. All samples were continuously collected from October to December 2017 in Tai'an, China. The presence of the mcr-1 gene in the strains was assessed by PCR. The genetic relationships of the polymyxin (POL)-resistant E. coli strains were analyzed by pulsed-field gel electrophoresis and multilocus sequence typing. The results indicate that the POL resistance rate for the E. coli isolates from poultry was 31.03% (27 of 87), whereas the human-origin E. coli isolates were 100% sensitive to POL. The mcr-1 gene and extended-spectrum ß-lactamase blaCTX-M-14 genes were identified in all 27 POL-resistant avian-origin E. coli isolates. Our pulsed-field gel electrophoresis analysis suggested that the 27 strains were represented by 14 pulsotypes, among which there were 3 strains each with A, E, I, and K pulsotypes, and 1 to 2 strains represented by the other 10 pulsotypes. Furthermore, multilocus sequence typing molecular typing identified 16 sequence types, including 4 ST156 strains, 3 ST533 strains, and 1 to 2 strains represented by the remaining 14 sequence types. In summary, the E. coli strains isolated in the Tai'an area all showed the MDR phenotype, the rate of which for poultry was higher than that for humans. No POL-resistant human-origin E. coli strains were identified in the clinical patients. Our study reveals that poultry-derived MDR mcr-1-positive E. coli strains may pose a potential risk to humans, and the surveillance findings presented herein will be conducive to our understanding of the prevalence and characteristics of mcr-1-positive E. coli strains in the Tai'an area.

13.
BMC Genet ; 21(1): 112, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32957918

RESUMO

BACKGROUND: In order to study the relations of hepatocellular functions, weight gain and metabolic imbalance caused by low-dose antibiotics (LDA) via epigenetic regulation of gene transcription, 32 weaned piglets were employed as animal models and randomly allocated into two groups with diets supplemented with 0 or LDA (chlorotetracycline and virginiamycin). RESULTS: During the 4 weeks of the experiment, LDA showed a clear growth-promoting effect, which was exemplified by the significantly elevated body weight and average daily gain. Promoter methylome profiling using liquid hybridization capture-based bisulfite sequencing (LHC-BS) indicated that most of the 745 differential methylation regions (DMRs) were hypermethylated in the LDA group. Several DMRs were significantly enriched in genes related with fatty acids metabolic pathways, such as FABP1 and PCK1. In addition, 71 differentially expressed genes (DEGs) were obtained by strand-specific transcriptome analysis of liver tissues, including ALOX15, CXCL10 and NNMT, which are three key DEGs that function in lipid metabolism and immunity and which had highly elevated expression in the LDA group. In accordance with these molecular changes, the lipidome analyses of serum by LC-MS identified 38 significantly differential lipids, most of which were downregulated in the LDA group. CONCLUSIONS: Our results indicate that LDA could induce epigenetic and transcriptional changes of key genes and lead to enhanced efficiency of lipid metabolism in the liver.

14.
Sci Adv ; 6(27)2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32937461

RESUMO

ß-Lactam-resistant (BLR) Gram-negative bacteria that are difficult or impossible to treat are causing a global health threat. However, the development of effective nanoantibiotics is limited by the poor understanding of changes in the physical nature of BLR Gram-negative bacteria. Here, we systematically explored the nanomechanical properties of a range of Gram-negative bacteria (Salmonella, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae) with different degrees of ß-lactam resistance. Our observations indicated that the BLR bacteria had cell stiffness values almost 10× lower than that of ß-lactam-susceptible bacteria, caused by reduced peptidoglycan biosynthesis. With the aid of numerical modeling and experimental measurements, we demonstrated that these stiffness findings can be used to develop programmable, stiffness-mediated antimicrobial nanowires that mechanically penetrate the BLR bacterial cell envelope. We anticipate that these stiffness-related findings will aid in the discovery and development of novel treatment strategies for BLR Gram-negative bacterial infections.

15.
Zhongguo Zhong Yao Za Zhi ; 45(16): 3844-3851, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893579

RESUMO

To optimize the formulation and preparation process of icaritin-coix seed oil microemulsion(IC-MEs) based on quality by design(QbD) concept. IC-MEs were prepared by water titration. Firstly, the risk factors that may affect the quality of IC-MEs were evaluated. Then Plackett-Burman design was used to screen out prescription factors and process parameters that had a significant effect on the indicators. Finally, Box-Behnken design was used to optimize the prescription ratio of IC-MEs. Through the risk assessment and Plackett-Burman design, three formulation factors [drug loading efficiency, the ratio of mixed-oil(coix seed oil-Glycerol tributyrate) to mixed-surfactant(HS15-RH40) and water addition] were determined as the key factors affecting IC-MEs. The regression model established by Box-Behnken design had a good predictability. The optimal formula was as following: the drug loading efficiency of 0.92%, the ratio of mixed-oil(coix seed oil-glycerol tributyrate) to mixed-surfactant(HS15-RH40) of 4∶6, and the water addition of 5.7 mL. According to this prescription, IC-MEs were prepared, and its encapsulation efficiency after 1 week was 92.45%±1.00%. Therefore, the stability of IC-MEs could be improved by optimizing prescription and process parameters of IC-MEs based on the QbD concept, which can provide certain reference value for the future development of IC-MEs.


Assuntos
Coix , Emulsões , Flavonoides , Óleos Vegetais
16.
Artigo em Inglês | MEDLINE | ID: mdl-32750980

RESUMO

The classification of six types of white blood cells (WBCs) is considered essential for leukemia diagnosis, while the classification is labor-intensive and strict with the clinical experience. To relieve the complicated process with an efficient and automatic method, we propose the Attention-aware Residual Network based Manifold Learning model (ARML) to classify WBCs. The proposed ARML model leverages the adaptive attention-aware residual learning to exploit the category-relevant image-level features and strengthen the first-order feature representation ability. To learn more discriminatory information than the first-order ones, the second-order features are characterized. Afterwards, ARML encodes both the first- and second-order features with Gaussian embedding into the Riemannian manifold to learn the underlying non-linear structure of the features for classification. ARML can be trained in an end-to-end fashion, and the learnable parameters are iteratively optimized. 10800 WBCs images (1800 images for each type) is collected, 9000 images and five-fold cross-validation are used for training and validation of the model, while additional 1800 images for testing. The results show that ARML achieving average classification accuracy of 0.953 outperforms other state-of-the-art methods with fewer trainable parameters. In the ablation study, ARML achieves improved accuracy against its three variants: without manifold learning (AR), without attention-aware learning (RML), and AR without attention-aware learning. The t-SNE results illustrate that ARML has learned more distinguishable features than the comparison methods, which benefits the WBCs classification. ARML provides a clinically feasible WBCs classification solution for leukemia diagnose with an efficient manner.

17.
Psychophysiology ; : e13653, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32749002

RESUMO

The influence of the language context on language control has been widely discussed in the bilingualism literature, and there is an increase in studies examining the effect of language context on domain-general executive control. However, it remains unclear how language contexts affect executive control performance. In the present study, we created single- and mixed-language comprehension contexts. Unbalanced Chinese-English bilinguals completed a modified flanker task that was interleaved with a single-language or mixed-language picture-word matching task. The effects of language comprehension context on language control were reflected by the N2 and LPC effects. Executive control processes also differed depending on the language comprehension context, with faster behavioral responses and larger N2 but smaller P3 electrophysiological components in the mixed-language context. Moreover, the LPC amplitude in the mixed-language context predicted the behavioral performance in the executive control task. These findings suggested that flexible language control during language comprehension altered executive control processes in unbalanced bilinguals.

18.
Clin Cancer Res ; 26(17): 4670-4681, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32732224

RESUMO

PURPOSE: Despite promising advances in breast cancer immunotherapy, augmenting T-cell infiltration has remained a significant challenge. Although neither individual vaccines nor immune checkpoint blockade (ICB) have had broad success as monotherapies, we hypothesized that targeted vaccination against an oncogenic driver in combination with ICB could direct and enable antitumor immunity in advanced cancers. EXPERIMENTAL DESIGN: Our models of HER2+ breast cancer exhibit molecular signatures that are reflective of advanced human HER2+ breast cancer, with a small numbers of neoepitopes and elevated immunosuppressive markers. Using these, we vaccinated against the oncogenic HER2Δ16 isoform, a nondriver tumor-associated gene (GFP), and specific neoepitopes. We further tested the effect of vaccination or anti-PD-1, alone and in combination. RESULTS: We found that only vaccination targeting HER2Δ16, a driver of oncogenicity and HER2-therapeutic resistance, could elicit significant antitumor responses, while vaccines targeting a nondriver tumor-specific antigen or tumor neoepitopes did not. Vaccine-induced HER2-specific CD8+ T cells were essential for responses, which were more effective early in tumor development. Long-term tumor control of advanced cancers occurred only when HER2Δ16 vaccination was combined with αPD-1. Single-cell RNA sequencing of tumor-infiltrating T cells revealed that while vaccination expanded CD8 T cells, only the combination of vaccine with αPD-1 induced functional gene expression signatures in those CD8 T cells. Furthermore, we show that expanded clones are HER2-reactive, conclusively demonstrating the efficacy of this vaccination strategy in targeting HER2. CONCLUSIONS: Combining oncogenic driver targeted vaccines with selective ICB offers a rational paradigm for precision immunotherapy, which we are clinically evaluating in a phase II trial (NCT03632941).

19.
Proc Natl Acad Sci U S A ; 117(33): 20305-20315, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32737160

RESUMO

Posttranslational modifications (PTMs) of α-synuclein (α-syn), e.g., phosphorylation, play an important role in modulating α-syn pathology in Parkinson's disease (PD) and α-synucleinopathies. Accumulation of phosphorylated α-syn fibrils in Lewy bodies and Lewy neurites is the histological hallmark of these diseases. However, it is unclear how phosphorylation relates to α-syn pathology. Here, by combining chemical synthesis and bacterial expression, we obtained homogeneous α-syn fibrils with site-specific phosphorylation at Y39, which exhibits enhanced neuronal pathology in rat primary cortical neurons. We determined the cryo-electron microscopy (cryo-EM) structure of the pY39 α-syn fibril, which reveals a fold of α-syn with pY39 in the center of the fibril core forming an electrostatic interaction network with eight charged residues in the N-terminal region of α-syn. This structure composed of residues 1 to 100 represents the largest α-syn fibril core determined so far. This work provides structural understanding on the pathology of the pY39 α-syn fibril and highlights the importance of PTMs in defining the polymorphism and pathology of amyloid fibrils in neurodegenerative diseases.


Assuntos
Doença de Parkinson , alfa-Sinucleína/química , Amiloide/química , Amiloide/metabolismo , Animais , Células Cultivadas , Microscopia Crioeletrônica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Modelos Moleculares , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosforilação , Conformação Proteica , Ratos , Ratos Sprague-Dawley , alfa-Sinucleína/síntese química , alfa-Sinucleína/metabolismo
20.
Gut Microbes ; 12(1): 1794466, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-32752913

RESUMO

The gut microbiome in newborns may be strongly influenced by their intrinsic host microenvironmental factors (e.g., the gestational age) and has been linked to their short-term growth and potentially future health. It is yet unclear whether early microbiota composition is significantly different in newborns conceived by assisted reproductive technology (ART) when compared with those who were conceived spontaneously. Additionally, little is known about the effect of gut microbiota composition on weight gain in early infancy. We aimed to characterize the features and the determinants of the gut microbiome in ART newborns and to assess the impact of early microbiota composition on their weight gain in early infancy in mother-infant dyads enrolled in the China National Birth Cohort (CNBC). Among 118 neonates born by ART and 91 neonates born following spontaneous conception, we observed significantly reduced gut microbiota α-diversity and declined Bacteroidetes relative abundance in ART neonates. The microbiota composition of ART neonates was largely driven by specific ART treatments, hinting the importance of fetus intrinsic host microenvironment on the early microbial colonization. Following up these neonates for six months after their births, we observed the effects of gut microbiome composition on infant rapid weight gaining. Collectively, we identified features and determinants of the gut microbiota composition in ART neonates, and provided evidence for the importance of microbiota composition in neonatal growth.

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