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OBJECTIVES: Clarifying the uncertain causal relationship between periodontitis and infective endocarditis using Mendelian randomization analysis, given their historically perceived association and clinical significance. METHODS: Genetic variation data for acute periodontitis, chronic periodontitis, aggressive periodontitis, and infective endocarditis were obtained from published GWAS in individuals of European ancestry. Instrumental variables significantly associated with periodontitis were selected and univariable Mendelian randomization was conducted to infer the causal association between periodontitis and infective endocarditis. Multivariable Mendelian randomization was also performed to adjust for potential confounders including smoking, drinking, diabetes, and education. RESULTS: Our analysis found no evidence of a causal association between periodontitis and infective endocarditis, with odds ratios (ORs) of 0.992 (95% CI: 0.879-1.120), 0.947 (95% CI: 0.738-1.214), and 1.056 (95% CI: 0.916-1.217) for acute periodontitis, chronic periodontitis, aggressive periodontitis, respectively. The robustness of our findings was confirmed by heterogeneity tests, pleiotropy tests, leave-one-out analyses, and MR-PRESSO. In the multivariable MR analysis, adjusting for smoking, drinking, diabetes, and education, the overall patterns between genetic liability to periodontitis and infective endocarditis remained consistent (all P > .05). CONCLUSION: Our findings indicate that there is no genetic causal association between periodontitis and infective endocarditis.
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Conventional plasma electrolytic oxidation treatments produce oxide coatings with micron-scale discharge pores, resulting in insulation and wear and corrosion resistance far below that expected of highly dense Al2O3 coatings. The introduction of cathodic polarization during the plasma electrolytic oxidation process, especially when the applied cathode-to-anode current ratio (Rpn) is greater than 1, triggers a unique plasma discharge phenomenon known as "soft sparking". The soft spark discharge mode significantly improves the densification of the anode ceramic layer and facilitates the formation of the high-temperature α-Al2O3 phase within the coating. Although the soft spark discharge phenomenon has been known for a long time, the growth behavior of the coating under its discharge mode still needs to be studied and improved. In this paper, the growth behavior of the coating before and after soft spark discharge is investigated with the help of the micro-morphology, phase composition and element distribution of a homemade fixture. The results show that the ceramic layer grows mainly along the oxide-electrolyte direction before the soft spark discharge transformation; after the soft spark discharge, the ceramic layer grows along the oxide-substrate direction. It was also unexpectedly found that, under soft spark discharge, the silicon element only exists on the outside of the coating, which is caused by the large size and slow migration of SiO32-, which can only enter the ceramic layer and participate in the reaction through the discharge channel generated by the strong discharge. In addition, it was also found that the relative phase content of α-Al2O3 in the coating increased from 0.487 to 0.634 after 10 min of rotary spark discharge, which is an increase of 30.2% compared with that before the soft spark discharge transition. On the other hand, the relative phase content of α-Al2O3 in the coating decreased from 0.487 to 0.313 after 20 min of transfer spark discharge, which was a 55.6% decrease compared to that before the soft spark discharge transformation.
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The correlation between negative pulse and the black electrolyte properties of magnesium alloy micro-arc oxidation and the treated area was investigated by introducing a negative pulse electric field. The physical phase composition, microstructure, elemental distribution, and content of the coating were analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). The results showed that the introduction of negative pulses favored the generation of MgO and MgSiO3 contents in the coatings, and an increase in the MgO phase was found in the coatings formed in the failed electrolytes; the microporous size and microcracks of the coatings were gradually and significantly reduced; the average consumption of Cu ions was 0.0453 g/L·dm2, which is only 26% of that in the unipolar condition; the introduction of the negative pulses significantly improved the "anomalous consumption" of Cu ions. The introduction of negative pulse can significantly improve the "abnormal consumption" of copper ions, which is attributed to the change in the electric field by negative pulse, which makes the cathode-enriched Cu ions migrate to the anode and reduces the reduction and precipitation of Cu ions at the cathode.
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In this paper, we establish a multi-stage fiber amplifier with pseudo-random binary sequence (PRBS) phase modulation. The stimulated Brillouin gain spectra of the main amplifier with both the unmodulated and pseudo-random binary sequence phase modulated configuration are measured (with corresponding output power), and the stimulated Brillouin scattering (SBS) threshold is investigated experimentally and theoretically. The pseudo-random binary sequence phase modulation parameters are optimized by theoretical simulation. With a two-stage preamplifier chain and a counter-pumping main amplifier stage, a maximum 3.05 kW output power with a slope efficiency of 85.9% is obtained experimentally. The central wavelength of the fiber amplifier is 1050 nm, associated with a full-width at half-maximum linewidth of 13.7 GHz. The stimulated Brillouin scattering reflectivity is below 0.01% at 3.05 kW at 13.7 GHz, which indicates that stimulated Brillouin scattering can be suppressed efficiently at this power and linewidth level.
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The cost-effective treatment of sludge leachate (SL) with high nitrogen content and refractory dissolved organic matter (rDOM) has drawn increasing attention. This study employed, for the first time, a rDOM triggered denitratation-anammox continuous-flow process to treat landfill SL. Moreover, the mechanisms of exploiting rDOM from SL as an inner carbon source for denitratation were systematically analyzed. The results demonstrated outstanding nitrogen and rDOM removal performance without any external carbon source supplement. In this study, effluent concentrations of 4.27 ± 0.45 mgTIN/L and 5.58 ± 1.64 mgTN/L were achieved, coupled with an impressive COD removal rate of 65.17 % ± 1.71 %. The abundance of bacteria belonging to the Anaerolineaceae genus, which were identified as rDOM degradation bacteria, increased from 18.23 % to 35.62 %. As a result, various types of rDOM were utilized to different extents, with proteins being the most notable, except for lignins. Metagenomic analysis revealed a preference for directing electrons towards NO3--N reductase rather than NO2--N reductase, indicating the coupling of denitratation bacteria and anammox bacteria (Candidatus Brocadia). Overall, this study introduced a novel synergy platform for advanced nitrogen removal in treating SL using its inner carbon source. This approach is characterized by low energy consumption and operational costs, coupled with commendable efficiency.
Subject(s)
Nitrogen , Sewage , Sewage/microbiology , Waste Disposal, Fluid/methods , Bacteria/metabolism , Water Pollutants, Chemical , DenitrificationABSTRACT
BACKGROUND: Bosma arhinia microphthalmia syndrome (BAMS; MIM603457) is a rare genetic disorder, predominantly autosomal dominant. It is a multi-system developmental disorder characterized by severe hypoplasia of the nose and eyes, and reproductive system defects. BAMS is extremely rare in the world and no cases have been reported in Chinese population so far. Pathogenic variants in the SMCHD1 gene (MIM614982) cause BAMS, while the underlying molecular mechanisms requires further investigation. CASE PRESENTATION: In this study, a Chinese girl who has suffered from congenital absence of nose and microphthalmia was enrolled and subsequently submitted to a comprehensive clinical and genetic evaluation. Whole-exome sequencing (WES) was employed to identify the genetic entity of thisgirl. A heterozygous pathogenic variant, NM_015295, c.1025G > C; p. (Trp342Ser) of SMCHD1 was identified. By performing very detailed physical and genetic examinations, the patient was diagnosed as BAMS. CONCLUSION: This report is the first description of a variant in SMCHD1 in a Chinese patient affected with BAMS.Our study not only furnished valuable genetic data for counseling of BAMS, but also confirmed the diagnosis of BAMS, which may help the management and prognosis for this patient.
Subject(s)
Choanal Atresia , Chromosomal Proteins, Non-Histone , Microphthalmos , Humans , Microphthalmos/genetics , Female , Chromosomal Proteins, Non-Histone/genetics , Choanal Atresia/genetics , China , Asian People/genetics , Nose/abnormalities , Exome Sequencing , East Asian PeopleABSTRACT
The establishment of left-right asymmetry is a fundamental process in animal development. Interference with this process leads to a range of disorders collectively known as laterality defects, which manifest as abnormal arrangements of visceral organs. Among patients with laterality defects, congenital heart diseases (CHD) are prevalent. Through multiple model organisms, extant research has established that myosin-Id (MYO1D) deficiency causes laterality defects. This study investigated over a hundred cases and identified a novel biallelic variant of MYO1D (NM_015194: c.1531G>A; p.D511N) in a consanguineous family with complex CHD and laterality defects. Further examination of the proband revealed asthenoteratozoospermia and shortened sperm. Afterward, the effects of the D511N variant and another known MYO1D variant (NM_015194: c.2293C>T; p.P765S) were assessed. The assessment showed that both enhance the interaction with ß-actin and SPAG6. Overall, this study revealed the genetic heterogeneity of this rare disease and found that MYO1D variants are correlated with laterality defects and CHD in humans. Furthermore, this research established a connection between sperm defects and MYO1D variants. It offers guidance for exploring infertility and reproductive health concerns. The findings provide a critical basis for advancing personalized medicine and genetic counseling.
Subject(s)
Heart Defects, Congenital , Spermatozoa , Humans , Male , Heart Defects, Congenital/genetics , Spermatozoa/abnormalities , Pedigree , Female , Adult , Myosin Type I/genetics , MutationABSTRACT
We report a theoretical and experimental study on stimulated Brillouin scattering (SBS) suppression in a monolithic fiber amplifier with filtered and amplified pseudo-random binary sequence (PRBS) phase modulation. Theoretically, we use a time-dependent three-wave coupled nonlinear system considering both active fiber and passive fiber to describe the acoustic phonon, laser, and Stokes characteristics in a fiber amplifier. The SBS threshold power after filtered PRBS phase modulation is numerically evaluated to obtain the optimal parameters, and the time-averaged distributions of the counter-pump power, laser power, and Stokes power at different positions along the fiber length of the fiber system are simulated. Also, we established a four-stage fiber amplifier system to verify our theory. The configuration of the fiber amplifier system includes a filtered and amplified PRBS phase-modulated single-frequency fiber laser, a three-stage pre-amplifier, and a counter-pumping main stage, subsequently. 2.5â kW output power with an FWHM linewidth of 9.63â GHz is accomplished by a domestic ytterbium-doped double-clad fiber with core/cladding diameters of 20.2/400â â µm. The reflectivity of the main stage is 0.049 at the maximum output power, which indicates the proposed architecture is under the SBS threshold. The experiments verify the accuracy of the theoretical model, which provides a reliable reference for evaluating the SBS suppression capability of the high-power narrow-linewidth fiber amplifier phase modulated by the filtered and amplified PRBS signal.
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Background: The primary imaging markers for idiopathic Normal Pressure Hydrocephalus (iNPH) emphasize morphological measurements within the ventricular system, with no attention given to alterations in brain parenchyma. This study aimed to investigate the potential effectiveness of combining ventricular morphometry and cortical structural measurements as diagnostic biomarkers for iNPH. Methods: A total of 57 iNPH patients and 55 age-matched healthy controls (HC) were recruited in this study. Firstly, manual measurements of ventricular morphology, including Evans Index (EI), z-Evans Index (z-EI), Cella Media Width (CMW), Callosal Angle (CA), and Callosal Height (CH), were conducted based on MRI scans. Cortical thickness measurements were obtained, and statistical analyses were performed using surface-based morphometric analysis. Secondly, three distinct models were developed using machine learning algorithms, each based on a different input feature: a ventricular morphology model (LVM), a cortical thickness model (CT), and a fusion model (All) incorporating both features. Model performances were assessed using 10-fold cross validation and tested on an independent dataset. Model interpretation utilized Shapley Additive Interpretation (SHAP), providing a visualization of the contribution of each variable in the predictive model. Finally, Spearman correlation coefficients were calculated to evaluate the relationship between imaging biomarkers and clinical symptoms. Results: iNPH patients exhibited notable differences in cortical thickness compared to HC. This included reduced thickness in the frontal, temporal, and cingulate cortices, along with increased thickness in the supracentral gyrus. The diagnostic performance of the fusion model (All) for iNPH surpassed that of the single-feature models, achieving an average accuracy of 90.43%, sensitivity of 90.00%, specificity of 90.91%, and Matthews correlation coefficient (MCC) of 81.03%. This improvement in accuracy (6.09%), sensitivity (11.67%), and MCC (11.25%) compared to the LVM strategy was significant. Shap analysis revealed the crucial role of cortical thickness in the right isthmus cingulate cortex, emerging as the most influential factor in distinguishing iNPH from HC. Additionally, significant correlations were observed between the typical triad symptoms of iNPH patients and cortical structural alterations. Conclusion: This study emphasizes the significant role of cortical structure changes in the diagnosis of iNPH, providing a novel insights for assisting clinicians in improving the identification and detection of iNPH.
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Intra-articular trauma typically initiates the overgeneration of reactive oxidative species (ROS), leading to post-traumatic osteoarthritis and cartilage degeneration. Xanthan gum (XG), a branched polysaccharide, has shown its potential in many biomedical fields, but some of its inherent properties, including undesirable viscosity and poor mechanical stability, limit its application in 3D printed scaffolds for cartilage regeneration. In this project, we developed 3D bioprinted XG hydrogels by modifying XG with methacrylic (MA) groups for post-traumatic cartilage therapy. Our results demonstrated that the chemical modification optimized the viscoelasticity of the bioink, improved printability, and enhanced the mechanical properties of the resulting scaffolds. The XG hydrogels also exhibit decent ROS scavenging capacities to protect stem cells from oxidative stress. Furthermore, XGMA(H) (5% MA substitution) exhibited superior chondrogenic potential in vitro and promoted cartilage regeneration in vivo. These dual-functional XGMA hydrogels may provide a new opportunity for cartilage tissue engineering.
Subject(s)
Antioxidants , Hydrogels , Polysaccharides, Bacterial , Hydrogels/pharmacology , Hydrogels/therapeutic use , Hydrogels/chemistry , Antioxidants/pharmacology , Antioxidants/therapeutic use , Tissue Scaffolds/chemistry , Reactive Oxygen Species , Cartilage , RegenerationABSTRACT
Leukoaraiosis (LA) is strongly associated with impaired cognition and increased dementia risk. Determining effective and robust methods of identifying LA patients with mild cognitive impairment (LA-MCI) is important for clinical intervention and disease monitoring. In this study, an ensemble learning method that combines multiple magnetic resonance imaging (MRI) morphological features is proposed to distinguish LA-MCI patients from LA patients lacking cognitive impairment (LA-nCI). Multiple comprehensive morphological measures (including gray matter volume (GMV), cortical thickness (CT), surface area (SA), cortical volume (CV), sulcus depth (SD), fractal dimension (FD), and gyrification index (GI)) are extracted from MRI to enrich model training on disease characterization information. Then, based on the general extreme gradient boosting (XGBoost) classifier, we leverage a weighted soft-voting ensemble framework to ensemble a data-level resampling method (Fusion + XGBoost) and an algorithm-level focal loss (FL)-improved XGBoost model (FL-XGBoost) to overcome class-imbalance learning problems and provide superior classification performance and stability. The baseline XGBoost model trained on an original imbalanced dataset had a balanced accuracy (Bacc) of 78.20%. The separate Fusion + XGBoost and FL-XGBoost models achieved Bacc scores of 80.53 and 81.25%, respectively, which are clear improvements (i.e., 2.33% and 3.05%, respectively). The fused model distinguishes LA-MCI from LA-nCI with an overall accuracy of 84.82%. Sensitivity and specificity were also well improved (85.50 and 84.14%, respectively). This improved model has the potential to facilitate the clinical diagnosis of LA-MCI.
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OBJECTIVE: To understand the genotype and distribution of thalassemia in northern Guangxi. METHODS: The study subjects were 55,281 individuals who came to the Affiliated Hospital of Guilin Medical University for genetic diagnosis of thalassemia from January 2012 to August 2023. All of their household registration was in the precincts of Guibei District and its affiliated counties. Red blood cell parameters and hemoglobin analysis were used for thalassemia screening. Gap-PCR, PCR-reverse dot blot hybridization (PCR-RDB), and multicolor melting curve analysis (MMCA) were used to identify common thalassemia genes. Multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, and third-generation single-molecule real-time (SMRT) sequencing were employed to identify rare thalassemia genes. RESULTS: Among the 55,281 samples, 16,442 (29.74%) were diagnosed with thalassemia. The detection rates of α, ß, and α combined ß-thalassemia were 18.57%, 9.99% and 1.18%, respectively. Among ethnical groups, allele mutation frequency of thalassemia was the highest in Zhuang (44.97%), followed by Yao (40.11%), Dong (31.33%), Han (29.85%), Miao (24.31%), and Hui (20.6%). A total of 11,659 alleles (21.09%) of 8 types of α-thalassemia were identified in 55,281 samples, primarily --SEA (53.9%), followed by -α3.7 (21.3%), including rare alleles: --THAI (0.45%) and HKαα (0.38%). A total of 6367 (11.52%) and 14 types of ß-thalassemia alleles were identified, mainly CD41-42 (50.12%), followed by CD17 (22.22%), including rare alleles: ßCD37 (0.16%) and Gγ+ (Aγδß)0/ßN (0.05%). A total of 31 genotypes were detected in 10,264 cases of α-thalassemia, and the main types were --SEA/αα (53.23%), -α3.7/αα (19.15%), and -α4.2/αα (7.21%). A total of 34 genotypes were detected in 5525 cases of ß-thalassemia, and the main types were ßCD41-42/ßN (50.53%), ßCD17/ßN (21.77%), and ßIVS-II-654/ßN (12.16%). A total of 78 gene types were detected in 653 cases of α- and ß-thalassemia, and the main types were --SEA/αα, ßCD41-42/ßN (18.68%) and -α3.7/αα, ßCD41-42/ßN (13.02%). There were 580 cases (5.65%) of HbH disease (α0/α+), and 4 cases of Hemoglobin Bart's Hydrops Foetus syndrome (--SEA/--SEA). In addition, there were 92 cases (1.67%) of intermedia or severe types of ß-thalassemia (ß0/ß0, ß0/ß+, ß+/ß+), including 23 cases of combined α-thalassemia. Among the samples screened negative for thalassemia, 3.7% of them were found to carry thalassemia genes, and 91.35% of the genotypes were αWSα/αα, -α3.7/αα, and -α4.2/αα. In addition, 40.26% of αWSα/αα, 22.89% of -α3.7/αα, and 18.51% of -α4.2/αα had no hematological phenotype. CONCLUSION: The population in northern Guangxi exhibited rich ethnic diversity, with high allelic carrying rates among the Zhuang, Yao and Dong ethnic groups. Thalassemia gene mutations are diverse, encompassing a variety of gene types, with α thalassemia predominating, notably the --SEA/αα gene type. The prevalence of intermedia or severe types of thalassemia is not low, but there are still some carriers of thalassemia in people who are initially tested negative.
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BACKGROUND: Accurate segmentation of lung nodules is of great significance for early screening and diagnosis of lung cancer. PURPOSE: However, the heterogeneity of lung nodules and the similarities between them and other lung tissues make it difficult to accurately segment these nodules. As regards the use of deep learning to segment lung nodules, convolutional neural networks would gradually lead to errors accumulating at the network layer due to the presence of multiple upsampling and downsampling layers, resulting in poor segmentation results. METHODS: In this study, we developed a refined segmentation network (RS-Net) for lung nodule segmentation to solve this problem. Accordingly, the proposed RS-Net was first used to locate the core region of the lung nodules and to gradually refine the segmentation results of the core region. In addition, to solve the problem of misdetection of small-sized nodules owing to the imbalance of positive and negative samples, we devised an average dice-loss function computed on nodule level. By calculating the loss of each nodule sample to measure the overall loss, the network can address the misdetection problem of lung nodules with smaller diameters more efficiently. RESULTS: Our method was evaluated based on 1055 lung nodules from Lung Image Database Consortium data and a set of 120 lung nodules collected from Shanghai Chest Hospital for additional validation. The segmentation dice coefficients of RS-Net on these two datasets were 85.90% and 81.13%, respectively. The analysis of the segmentation effect of different properties and sizes of nodules indicates that RS-Net yields a stable segmentation effect. CONCLUSIONS: The results show that the segmentation strategy based on gradual refinement can considerably improve the segmentation of lung nodules.
Subject(s)
Lung Neoplasms , Tomography, X-Ray Computed , Humans , Tomography, X-Ray Computed/methods , China , Lung Neoplasms/diagnostic imaging , Lung/diagnostic imaging , Neural Networks, Computer , Image Processing, Computer-Assisted/methodsABSTRACT
The infinite-layer nickelates, isostructural to the high-Tc cuprate superconductors, have emerged as a promising platform to host unconventional superconductivity and stimulated growing interest in the condensed matter community. Despite considerable attention, the superconducting pairing symmetry of the nickelate superconductors, the fundamental characteristic of a superconducting state, is still under debate. Moreover, the strong electronic correlation in the nickelates may give rise to a rich phase diagram, where the underlying interplay between the superconductivity and other emerging quantum states with broken symmetry is awaiting exploration. Here, we study the angular dependence of the transport properties of the infinite-layer nickelate Nd0.8Sr0.2NiO2 superconducting films with Corbino-disk configuration. The azimuthal angular dependence of the magnetoresistance (R(φ)) manifests the rotational symmetry breaking from isotropy to four-fold (C4) anisotropy with increasing magnetic field, revealing a symmetry-breaking phase transition. Approaching the low-temperature and large-magnetic-field regime, an additional two-fold (C2) symmetric component in the R(φ) curves and an anomalous upturn of the temperature-dependent critical field are observed simultaneously, suggesting the emergence of an exotic electronic phase. Our work uncovers the evolution of the quantum states with different rotational symmetries in nickelate superconductors and provides deep insight into their global phase diagram.
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During the past decade, the average 5-year survival rate of patients with Lung adenocarcinoma (LUAD) has remained < 20%, although the targeted therapies and novel immunotherapy approaches have held promise. Epigenetic modifications could provide prognostic value as molecular biomarkers, and we aimed to identify the independent risk of m6A-related lncRNAs to establish a risk model for the clinical prediction of prognoses in women with LUAD. In this study, we first assessed 31 N6-methyladenosine (m6A)-related lncRNAs associated with overall survival. Moreover, we evaluated the expression of the oncogenic driver and the tumor immune microenvironment (TIME) in two female LUAD subtypes (clusters 1 and 2) using consensus clustering. We also found 16 m6A-related lncRNAs as the independent prognostic indicator of women with LUAD and established a risk model developed from these lncRNAs. We comprehensively investigated the correlation between the TIME and m6A-related lncRNA and found that m6A-related lncRNA may significantly affect the immune cell infiltration level in LUAD. In conclusion, our study provides evidence on the prognostic prediction in women with LUAD and may help elucidate the processes and mechanisms of m6A-regulated lncRNAs.
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The recent discovery of superconductivity in infinite-layer nickelates generates tremendous research endeavors, but the ground state of their parent compounds is still under debate. Here, we report experimental evidence for the dominant role of Kondo scattering in the underdoped Nd1-xSrxNiO2 thin films. A resistivity minimum associated with logarithmic temperature dependence in both longitudinal and Hall resistivities are observed in the underdoped Nd1-xSrxNiO2 samples before the superconducting transition. At lower temperatures down to 0.04 K, the resistivities become saturated, following the prediction of the Kondo model. A linear scaling behavior [Formula: see text] between anomalous Hall conductivity [Formula: see text] and conductivity [Formula: see text]is revealed, verifying the dominant Kondo scattering at low temperature. The effect of weak (anti-)localization is found to be secondary. Our experiments can help in clarifying the basic physics in the underdoped Nd1-xSrxNiO2 infinite-layer thin films.
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A sequencing batch reactor (SBR) was operated to investigate variations of extracellular polymeric substances (EPS) and microbial community during the start-up of the single-stage partial nitritation/anammox (SPN/A) process at intermittent aeration mode. The SPN/A system was successfully started on day 34, and the nitrogen removal efficiency and total nitrogen loading rate were 82.29% and 0.31 kg N/(m3 ·day), respectively. Furthermore, the relationship between the protein secondary structures and microbial aggregation was strongly related. The α-helix/ (ß-sheet + random coil) ratios increased obviously from 0.20 ± 0.03 to 0.23 ± 0.01, with the sludge aggregation mean size increased from 56 to 107 µm during the start-up of SPN/A. During the start-up of SPN/A, Candidatus Kuenenia was the primary anammox bacteria, whereas Nitrospira was the main functional bacteria of nitrite-oxidizing bacteria. Correlation between the microbial community and EPS components was performed. The EPS and microbial community played important roles in keeping stable nitrogen removal and the formation of sludge granules. PRACTITIONER POINTS: Intermittent aeration strategy promoted SPN/A system start-up. EPS composition and protein secondary structure were related with the sludge disintegration and aggregation. Microbial community shift existed and promoted the stability of sludge and reactor performance during SPN/A start-up.