Search

Cardiac fibrosis is a process characterized by extracellular matrix accumulation leading to myocardial dysfunction. Angiotensin II (Ang II) has been shown to play an important role in the pathogenesis of cardiac fibrosis. However, the underlying mechanisms are not well established. Dysfunction of adipose tissue has been shown to promote remote organ injury, but its role in Ang II-induced cardiac remodeling is still unclear. In this study, we demonstrated that epididymal white adipose tissue (eWAT) promoted Ang II-induced cardiac fibrosis and subsequent cardiac dysfunction in an exosome-dependent manner. Both eWAT removal and administration of an inhibitor of exosome biogenesis strongly attenuated Ang II-induced abnormalities. Moreover, exosomes isolated from Ang II-stimulated adipocytes promoted cardiac fibroblasts (CFs) activity. A mechanistic study identified that the miR-23a-3p level was significantly increased in exosomes derived from Ang II-challenged adipocytes and serum exosomes from Ang II-infused mice. Importantly, tail vein injection of ago-miR-23a-3p caused cardiac fibrosis and dysfunction, while antago-miR-23a-3p inhibited Ang II-induced cardiac fibrosis. Bioinformatics analysis and further validation experiments revealed that RAP1 is a direct downstream target of miR-23a-3p, and overexpression of RAP1 reversed the profibrotic effect of miR-23a-3p. Taken together, these findings elucidated the role of eWAT in Ang II-induced myocardial fibrosis and indicated that adipocyte-derived exosomes mediate pathologic communication between dysfunctional adipose tissue and the heart by transporting miR-23a-3p into CFs, transforming fibroblasts into myofibroblasts and promoting excessive collagen deposition by targeting RAP1. Prevention of abnormal adipocyte exosome production, inhibition of miR-23a-3p biogenesis, and treatment with a miR-23a-3p antagonist are novel strategies for treating cardiac fibrosis.

To establish the cross-sectional reference values of cerebral ventricular size for the Chinese newborns by the most correlated explanatory variables. The anterior horn width (AHW), thalamo-occipital distance (TOD), and ventricular index (VI) were collected prospectively from 1- to 7-day neonates without potential neurological problems. All neonates were delivered or treated at the Hunan Provincial Maternal and Child Health Care Hospital or Second Xiangya Hospital of Central South University between February and August 2021. The most correlated explanatory variables were identified with the max-min normalization and multiple regression. The reference values were then established based on the above variables. Additionally, intraclass correlation coefficients (ICC) were applied to evaluate the reliability of the overall data collection process. This prospective study consisted of 1848 neonates. The AHW was most highly correlated with GA; the TOD and VI were most strongly correlated with birth weight. All the foregoing correlations were positive ones. Heteroscedasticity and influential points existed in both TOD and VI. The ICCWe recommend using the GA-based AHW reference values and birth weight-based TOD and VI ones. We also present a comparison of GA-based upper limits from all available reference intervals. Moreover, we determine that measurement errors are the primary cause of influential points and heteroscedasticity in TOD and VI studies and infer that the studies of TOD and VI are vulnerable to them.• Reference values of infantile cerebral ventricles are vital in diagnosing and treating cerebral ventricular dilatation. • Precursors established gestational age-based reference values subjectively.• We set cross-sectional reference values based on the most correlated variables for Chinese neonates and compared all available gestational age-based upper limits. • Influential points and heteroscedasticity mainly caused by measurement errors are common in TOD and VI studies.

This study aimed to ascertain whether the lower anterior myometrial thickness (MT) between the bladder and the gestational sac in early pregnancy can be used to predict clinical outcomes in women with cesarean scar pregnancy (CSP) after expectant management.We retrospectively analyzed the clinical data and early pregnancy ultrasound images of 21 patients who received expectant management for CSP. Among them, 11 patients with serious complications during pregnancy, such as intraoperative blood loss ≥1000 mL or with severe forms of morbidly adherent placenta (MAP; placenta increta or placenta percreta), were assigned to group A. The remaining 10 patients without serious complications during pregnancy were assigned to group B. The difference in MT between groups A and B was analyzed using nonparametric Mann-Whitney U test.There was a statistically significant difference in MT between the groups (U = 20.000, p = 0.013). The area under the receiver operating characteristics (ROC) curve was 0.818, and the optimal cut-off value for MT was 3.3 mm.Lower anterior MT around the gestational sac was correlated with severe complications, such as massive intraoperative bleeding or severe forms of MAP in patients with CSP.

C24H16Br2N2O4Zn, monoclinic, I2/a (no. 15), a = 7.4191(9) Å, b = 24.458(3) Å, c = 25.810(3) Å, β = 92.426(3)°, V = 4679.2(10) Å3, Z = 8, R gt (F) = 0.0514, wR ref (F 2) = 0.1710, T = 296(2) K.

Background: Accurate annotation of protein function is the key to understanding life at the molecular level and has great implications for biomedicine and pharmaceuticals. The rapid developments of high-throughput technologies have generated huge amounts of protein-protein interaction (PPI) data, which prompts the emergence of computational methods to determine protein function. Plagued by errors and noises hidden in PPI data, these computational methods have undertaken to focus on the prediction of functions by integrating the topology of protein interaction networks and multi-source biological data. Despite effective improvement of these computational methods, it is still challenging to build a suitable network model for integrating multi-omics data. ResultsIn this paper, we constructed a heterogeneous biological network by initially integrating original protein interaction networks, protein-domain association data and protein complexes. To prove the effectiveness of the heterogeneous biological network, we applied the propagation algorithm on this network, and proposed a novel iterative model, named PHN (Propagate on Heterogeneous Biological Networks) to score and rank functions in descending order from all functional partners and selected the first L of them as candidates to annotate the target protein. Our comprehensive experimental results demonstrated that PHN outperformed six other competing approaches using cross validation. Experimental results indicated that PHN performs significantly better than competing methods and improves the AUROC (Area Under the Receiver-Operating Curve) by no less than 32%.Conclusions:We demonstrated that integrating multi-source data into a heterogeneous biological network can preserve the complex relationship among multi-omics data and improve the prediction accuracy of protein function by getting rid of the the constraints of errors in PPI networks effectively. PHN, our proposed method, is effective for protein function prediction.

This study demonstrates an accurate method for determining the moisture content in flavor microcapsules using headspace gas chromatography. The method involves measuring the gas chromatography signals of water from vapor in a headspace vial containing flavor microcapsules at a temperature of 125 °C. The measurements were recorded over four headspace extractions, from which the moisture content in the microcapsule samples was extrapolated via simple vapor-phase calibration. The results revealed that the proposed method demonstrated good precision (a relative standard deviation of

To explore the feasibility of the fetal heart quantitative technique (fetalHQ) for evaluating the sphericity index (SI) of the fetal heart during middle and late pregnancy.Ninety-six normal fetuses in middle and late gestation who underwent systemic ultrasound examination in the Department of Ultrasound of the Maternal and Child Health Care Hospital of Hunan Province in November 2020 were enrolled, and dynamic images of the four-chamber view of the fetal heart were collected. The correlation between the global sphericity index (GSI), ventricular 24-segment SI, and gestational age (GA) was analyzed, and the differences between the left and right ventricular 24-segment SI were compared.The success rate of fetalHQ analysis was 93.75%. There was no significant linear correlation between GSI and ventricular 24-segment SI and GA (allFetalHQ is a simple and reliable method for evaluating the GSI and 24-segment SI of the left and right ventricles. It can provide some theoretical basis for the clinical quantitative evaluation of fetal heart geometry and lay a foundation for the quantitative evaluation of fetal heart function in cases of structural and functional abnormalities.

Aims Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-related diseases. However, whether the aged-associated dysbiosis contributes to age-related AF is still unknown. Direct demonstration that the aged gut microbiota is sufficient to transmit the enhanced AF susceptibility in a young host via microbiota-intestinal barrier-atria axis has not yet been reported. This study aimed to determine whether gut microbiota dysbiosis affects age-related AF. Methods and results Herein, by using a fecal microbiota transplantation (FMT) rat model, we demonstrated that the high AF susceptibility of aged rats could be transmitted to a young host. Specially, we found the dramatically increased levels of circulating lipopolysaccharide (LPS) and glucose led to the up-regulated expression of NLR family pyrin domain containing 3 (NLRP3)-inflammasome, promoting the development of AF which depended on the enhanced atrial fibrosis in recipient host. Inhibition of inflammasome by a potent and selective inhibitor of the NLRP3 inflammasome, MCC950, resulted in a lower atrial fibrosis and AF susceptibility. Then we conducted cross-sectional clinical studies to explore the effect of aging on the altering trends with glucose levels and circulating LPS among clinical individuals in two China hospitals. We found that both of serum LPS and glucose levels were progressively increased in elderly patients as compared with those young. Furthermore, the aging phenotype of circulating LPS and glucose levels, intestinal structure and atrial NLRP3-inflammasome of rats were also confirmed in clinical AF patients. Finally, aged rats colonized with youthful microbiota restored intestinal structure and atrial NLRP3-inflammasome activity, which suppressed the development of aged-related AF. Conclusions Collectively, these studies described a novel causal role of aberrant gut microbiota in the pathogenesis of age-related AF, which indicates that the microbiota-intestinal barrier-atrial NLRP3 inflammasome axis may be a rational molecular target for the treatment of aged-related arrhythmia disease. Translational perspective The current study demonstrates that aged-associated microbiota dysbiosis promotes AF in part through a microbiota-gut-atria axis. Increased AF susceptibility due to enhanced atrial NLRP3-inflammasome activity by LPS and high glucose was found in an aged FMT rat model, and also confirmed within elderly clinical individuals. In a long-term FMT rat study, the AF susceptibility was ameliorated by treatment with youthful microbiota. The present findings can further increase our understanding of aged-related AF and address a promising therapeutic strategy that involves modulation of gut microbiota composition.

Developing highly efficient and stable electrocatalysts for hydrogen evolution reaction (HER) is regarded as a crucial way to reduce energy loss in water splitting. Herein, NiSe2/MoSe2 heterostructures grown on graphene nanosheets (NiSe2-MoSe2 HTs/G) have been in situ synthesized by a simple hydrothermal reaction. As an electrocatalyst for HER, NiSe2-MoSe2 HTs/G delivers superior performance with a low Tafel slope of 65 mV dec−1, a small overpotential of 144 mV at 10 mA cm−2, and long-term stability up to 24 h. The superior performance for HER can be mainly ascribed to the synergistic effects of NiSe2-MoSe2 heterostructures, which can facilitate the rapid electron transfer from the electrode to the exposed MoSe2 edges to take part in the HER reaction, thus boosting the HER kinetics. Moreover, the graphene matrix with high conductivity can not only improve the overall conductivity of the composite but also greatly increase the exposed active sites, therefore further promoting the HER performance. This study provides a simple route for fabricating bimetallic selenides-based heterostructures on graphene as an efficient and stable electrocatalyst for HER.

Background Digital image technology has made great progress in the field of foreign body detection and classification, which is of great help to drug purity extraction and impurity analysis and classification. Objective The detection and classification of foreign bodies in lyophilized powder are important. The method which can obtain a higher accuracy of recognition needs to be proposed. Methods We used digital image technology to detect and classify foreign bodies in lyophilized powder, and studied the process of image preprocessing, median filtering, Wiener filtering and average filtering balance to better detect and classify foreign bodies in lyophilized powder. Results Through industrial small sample data simulation, test results show that in the process of image preprocessing, 3 × 3 median filtering is best. In the aspect of foreign body recognition, the recognition based on principal component analysis (PCA) and support vector machine (SVM) algorithm and the recognition based on PCA and Third-Nearest Neighbor classification algorithm are compared and results show that the PCA+SVM algorithm is better. Conclusion We demonstrated that integrating PCA and SVM to classify foreign bodies in lyophilized powder. Our proposed method is effective for the prediction of essential proteins.

Essential proteins are important for the survival and reproduction of organisms. Many computational methods have been proposed to identify essential proteins, due to the production of vast amounts of protein-protein interaction (PPI) data. It has been demonstrated that PPI networks have graph-theoretic characteristics as so-called small-world and scale-free. The traditional metrics cannot really reflect the relationship between proteins when identifying essential proteins from PPI networks. In this paper, we construct a diffusion distance network (DSN) by combining PPI topology characteristics with orthologous proteins and sub-cellular localization information of proteins. Taking the modularity feature of essential proteins into account, we proposed a new essential proteins prediction method based on DSN. We employed our DSN method and ten other state-of-the-art methods to predict essential proteins. The precision-recall curve, jackknife methodology and so on are used to test the performance of these methods. Experimental results show that our method outperform ten other competitive methods. The row data and the software are freely available at: https://github.com/husaiccsu/DSN .

This study aimed to analyze the diagnostic value of multimodal images based on artificial intelligence target detection algorithms for early breast cancer, so as to provide help for clinical imaging examinations of breast cancer. This article combined residual block with inception block, constructed a new target detection algorithm to detect breast lumps, used deep convolutional neural network and ultrasound imaging in diagnosing benign and malignant breast lumps, took breast density grading with mammography, compared the convolutional neural network (CNN) algorithm with the proposed algorithm, and then applied the proposed algorithm to the diagnosis of 120 female patients with breast lumps. According to the results, accuracy rates of breast lump detection (94.76%), benign and malignant breast lumps diagnosis (98.22%), and breast grading (93.65%) with the algorithm applied in this study were significantly higher than those (75.67%, 87.23%, and 79.54%) with CNN algorithm, and the difference was statistically significant ( P P

Carbon nano-materials have been widely used in many fields due to their electron transport, mechanics, and gas adsorption properties. This paper introduces the structure and properties of carbon nano-materials the preparation of carbon nano-materials by chemical vapor deposition method (CVD)—which is one of the most common preparation methods—and reaction simulation. A major factor affecting the material structure is its preparation link. Different preparation methods or different conditions will have a great impact on the structure and properties of the material (mechanical properties, electrical properties, magnetism, etc.). The main influencing factors (precursor, substrate, and catalyst) of carbon nano-materials prepared by CVD are summarized. Through simulation, the reaction can be optimized and the growth mode of substances can be controlled. Currently, numerical simulations of the CVD process can be utilized in two ways: changing the CVD reactor structure and observing CVD chemical reactions. Therefore, the development and research status of computational fluid dynamics (CFD) for CVD are summarized, as is the potential of combining experimental studies and numerical simulations to achieve and optimize controllable carbon nano-materials growth.

Cornelia de Lange syndrome (CdLS) is a genetic disorder characterized by multisystemic malformations. Mutation in the NIPBL gene accounts for nearly 60% of the cases. This study reports the clinical and genetic findings of three cases of CdLS from unrelated Chinese families. Clinically, all the three cases were classified as classic CdLS based on the cardinal (distinctive facial features and limb malformations) and suggestive (developmental delay, growth retardation, microcephaly, hirsutism, etc.) manifestations. SNP array detected a novel de novo heterozygous microdeletion of 0.2 Mb [arr[GRCh37]5p13.2(36848530_37052821) × 1] that spans the first 43 exons of NIPBL in the fetus with nuchal translucency thickening in case 1. Whole-exome sequencing in family trios plus Sanger sequencing validation identified a de novo heterozygous NIPBL c.5566G>A (p.R1856G) mutation in the fetus with intrauterine growth retardation in case 2 and a novel de novo heterozygous NIPBL c.448dupA (p.S150Kfs*23) mutation in the proband (an 8-month-old girl) in case 3. The cases presented in this study may serve as references for increasing our understanding of the mutation spectrum of NIPBL in association with CdLS.

A new copper-thiolate cluster assembled framework [Cu2(µ4-SCH3)Cl]n (1), has been solvothermally synthesized through in situ reaction viz., in situ ligand generation and metal reduction. Compound 1 represents the first 3D framework based on Atlas-sphere functionalized by single µ2-Cl− groups. DOS calculation reveals the interaction of electronic structures. It is found that the HOMO is mainly distributed on Cl, Cu and S bonding orbitals, while the LUMO is dominated by Cu-Cl antibonding orbitals.

Aim We report tofacitinib efficacy and safety in Asia‐Pacific patients who participated in the rheumatoid arthritis (RA) clinical development program. Method This post‐hoc analysis included pooled data from patients with RA in the Asia‐Pacific region treated with tofacitinib with/without conventional synthetic disease‐modifying antirheumatic drugs in Phase (P)1, 2, 3, and long‐term extension (LTE) studies (one LTE ongoing; January 2016 data‐cut). Efficacy was assessed over 24 months in patients who received tofacitinib 5 (N = 397) or 10 (N = 382) mg twice daily or placebo (N = 243) in three P2 and five P3 studies. Endpoints included American College of Rheumatology (ACR)20/50/70 responses, Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28‐4[ESR]) and Clinical Disease Activity Index (CDAI) remission rates, and change from baseline in Health Assessment Questionnaire‐Disability Index (∆HAQ‐DI). Safety data pooled over 92 months from one P1, four P2, six P3, and two LTE studies for all tofacitinib doses (N = 1464) included incidence rates (IRs) (patients with events/100 patient‐years) for adverse events (AEs) of special interest. Results At month 3, patients receiving tofacitinib 5/10 mg twice daily improved vs placebo in ACR20 (69.2%/77.9% vs 27.5%), ACR50 (36.9%/44.4% vs 9.5%), and ACR70 (15.1%/22.4% vs 2.7%) responses, remission rates for DAS28‐4(ESR) (8.5%/18.5% vs 2.6%) and CDAI (6.1%/12.3% vs 0.5%), and ∆HAQ‐DI (−0.5/–0.6 vs −0.1); improvements were sustained through 24 months. IRs (95% CI) were 9.4 (8.5, 10.3) for serious AEs, 9.1 (8.3, 10.1) for discontinuations due to AEs, 3.7 (3.2, 4.3) for serious infections, 5.9 (5.2, 6.7) for herpes zoster, and 0.8 (0.6, 1.1) for malignancies (excluding non‐melanoma skin cancer). Conclusion In Asia‐Pacific patients, tofacitinib improved signs/symptoms over 24 months. Safety over 92 months was generally consistent with global tofacitinib studies; however, infection IRs were higher in Asia‐Pacific patients.

Aging plays a critical role in the genesis of atrial fibrillation (AF) and also changes the gut microbes. Whether the aging-associated gut dysbiosis contributes to the development of aging-related AF and whether the gut microbes can be a target to prevent aging-related AF remains unknown.16S rRNA gene sequencing was performed to reveal the changes of gut microbes in elderly patients with AF, and the result showed that the intestinal abundance of B. fragilis was significantly decreased in elderly patients with AF. Subsequently, we examined the impact of B. fragilis supplementation on AF promotion, atrial structural remodeling and inflammation response in D-galactose induced aging rats. We found that oral administration of B. fragilis prevented AF inducibility and duration, which was associated with attenuation of atrial senescence, apoptosis and fibrosis. Furthermore, B. fragilis significantly diminished the systemic and atrial inflammation, which is accompanied by an increase in the number of Treg cells in the spleen and blood. More importantly, we found that the circulation level of polysaccharide A (PSA), the metabolite synthesized by B. fragilis, was reduced in elderly patients with AF and could predict the occurrence of AF, and B. fragilis increased the circulation concentration of PSA in D-galactose induced aging rats.The abundance of B. fragilis was lower in elderly patients with AF. Oral administration of B. fragilis significantly attenuated inflammatory response by increasing Treg cells, thereby preventing atrial structural remodeling and inhibiting AF promotion in D-galactose induced aging rats. This study provides experimental evidence for the effectiveness of targeting gut microbes in the prevention of aging-related AF.

Background: The cleft lip with or without palate (CL/P) is the most prevalent congenital craniofacial abnormality. This study aims to provide molecular diagnosis for patients with CL/P in a Chinese family, and then offer suggestions for future pregnancy for this family.Methods: Karyotyping, single nucleotide polymorphism array analysis, whole-exome sequencing (WES), and Sanger sequencing were applied to identify the underlying genetic cause for the clinical phenotypes. The functional effect of the identified mutation was evaluated through immunofluorescent analysis of the expression of wild or mutant protein that was transiently expressed. Non-invasive prenatal testing (NIPT) and ultrasound testing were conducted for a new pregnancy of this family. Results: A novel missense mutation (c.1418T>A/p.(Val473Asp)) in CDH1 was identified in the family members affected with CL/P. Functional analysis showed that this mutation changed the subcellular localization of the protein. The NIPT and ultrasound testing respectively revealed the new pregnancy carried no CDH1 mutation and facial dysmorphic features, and a healthy baby was delivered.Conclusion: The affected family members were diagnosed with a syndromic CL/P called Blepharo-Cheilo-Dontic(BCD) Syndrome. This study identified a novel CDH1 mutation for CL/P, expanded the mutation spectrum, and contributed to the genetic diagnosis and counseling of this disorder. This study also provided an example of the application of NIPT for BCD Syndrome.

Rationale: Hydronephrosis, mostly caused by ureteropelvic junction obstruction, rarely occurs in infants. However, imperforate hymen atresia in female infants may cause hydronephrosis, even though it is rare. Patient concerns: A 3-month-old female infant was admitted to our hospital for frequent crying. There was no significant past medical history. Diagnoses: Following ultrasound imaging, the patient was diagnosed with hydronephrosis possibly caused by imperforate hymen. Interventions: The infant underwent hymenotomy with a cruciate incision to prevent future complications such as acute renal injury. Outcomes: Hydronephrosis resolved after the operation. The outcome was very good, with no complications in the postoperative period. Conclusions: Early ultrasound diagnosis plays a significant role in the management and treatment of infant patients. Ultrasound is the mandatory imaging technology for determining the cause of hydronephrosis.

Background: Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-associated diseases. However, whether age-associated gut microbial dysbiosis contributes to AF is still unknown. The aim of this study was to evaluate the effect of gut microbiota on the susceptibility of aging-induced AF and to elucidate the underlying mechanisms. Results: The gut microbiota profiling of fecal samples in aged (22-24 months old) and young (2-3 months old) rats was performed by 16S ribosomal RNA gene analysis. A rat model of fecal microbiota transplantation (FMT) was established for analyzing the possible role of age-associated gut microbial dysbiosis in AF. Here, we found that aging process led to marked shift of the microbiota spectrum. The microbiota in young rats following FMT resembled that of aged microbiota and transmitted the increased AF susceptibility by elevation of circulating lipopolysaccharide (LPS). The mechanism for LPS-driven atrial pro-arrhythmic action was dependent on the activation of atrial nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing (NLRP3)-inflammasome. Inhibition of inflammasome by MCC950 resulted in lower atrial fibrosis and AF susceptibility. In addition, atrial fibrosis, plasma LPS concentration, plasma glucose to oral glucose tolerance test (OGTT), intestinal permeability, and gut pathology were significantly increased in elderly human subjects. Finally, altering the microbiota in aged recipient to resemble that of young restored the intestinal barrier dysfunction and LPS and impaired glucose tolerance, and the worse outcomes of aged dysbiosis on atrial fibrosis and AF susceptibility were abrogated. Conclusions: These data suggest that age-associated microbial dysbiosis induces circulating LPS and impairs glucose tolerance, and thereby promotes AF susceptibility through enhanced activity of atrial NLRP3-inflammasome.

Background Essential proteins are an important part of the cell and closely related to the life activities of the cell. Hitherto, Protein-Protein Interaction (PPI) networks have been adopted by many computational methods to predict essential proteins. Most of the current approaches focus mainly on the topological structure of PPI networks. However, those methods relying solely on the PPI network have low detection accuracy for essential proteins. Therefore, it is necessary to integrate the PPI network with other biological information to identify essential proteins. Results In this paper, we proposed a novel random walk method for identifying essential proteins, called HEPT. A three-dimensional tensor is constructed first by combining the PPI network of Saccharomyces cerevisiae with multiple biological data such as gene ontology annotations and protein domains. Then, based on the newly constructed tensor, we extended the Hyperlink-Induced Topic Search (HITS) algorithm from a two-dimensional to a three-dimensional tensor model that can be utilized to infer essential proteins. Different from existing state-of-the-art methods, the importance of proteins and the types of interactions will both contribute to the essential protein prediction. To evaluate the performance of our newly proposed HEPT method, proteins are ranked in the descending order based on their ranking scores computed by our method and other competitive methods. After that, a certain number of the ranked proteins are selected as candidates for essential proteins. According to the list of known essential proteins, the number of true essential proteins is used to judge the performance of each method. Experimental results show that our method can achieve better prediction performance in comparison with other nine state-of-the-art methods in identifying essential proteins. Conclusions Through analysis and experimental results, it is obvious that HEPT can be used to effectively improve the prediction accuracy of essential proteins by the use of HITS algorithm and the combination of network topology with gene ontology annotations and protein domains, which provides a new insight into multi-data source fusion.

BackgroundThe accurate annotation of protein functions is of great significance in elucidating the phenomena of life, treating disease and developing new medicines. Various methods have been developed to facilitate the prediction of these functions by combining protein interaction networks (PINs) with multi-omics data. However, it is still challenging to make full use of multiple biological to improve the performance of functions annotation.ResultsWe presented NPF (Network Propagation for Functions prediction), an integrative protein function predicting framework assisted by network propagation and functional module detection, for discovering interacting partners with similar functions to target proteins. NPF leverages knowledge of the protein interaction network architecture and multi-omics data, such as domain annotation and protein complex information, to augment protein-protein functional similarity in a propagation manner. We have verified the great potential of NPF for accurately inferring protein functions. According to the comprehensive evaluation of NPF, it delivered a better performance than other competing methods in terms of leave-one-out cross-validation and ten-fold cross validation.ConclusionsWe demonstrated that network propagation, together with multi-omics data, can both discover more partners with similar function, and is unconstricted by the “small-world” feature of protein interaction networks. We conclude that the performance of function prediction depends greatly on whether we can extract and exploit proper functional information of similarity from protein correlations.

Additional file 1 Algorithm convergence. This file provides the proof of the Algorithm 1 convergence about the effect of parameter α and ∂ on the speed of convergence.

Background.There has been significant research on the genetic and environmental factors of congenital heart defects (CHDs), but few causes of teratogenicity, especially teratogenic mechanisms, can be clearly identified. Metabolomics has a potential advantage in researching the relationship between external factors and CHD.Objective.To find and identify the urinary potential biomarkers of pregnancy (including in the second and third trimesters) for fetuses with CHD based on modified gas chromatograph-mass spectrometer (GC-MS), which could reveal the possibility of high-risk factors for CHD and lay the foundation for early intervention, treatment, and prevention.Methods.Using a case-control design, we measured the urinary potential biomarkers of maternal urine metabolomics based on GC-MS in a population-based sample of women whose infants were diagnosed with CHD (70 case subjects) or were healthy (70 control subjects). SIMCA-P 13.0 software, principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), Wilcoxon-Mann-Whitney test, and logistics regression were used to find significant potential biomarkers.Result.The 3D score graph of the OPLS-DA showed that the CHD and control groups were fully separated. The fitting parameters were R2x=0.78 and R2y=0.69, and the forecast rate was Q2=0.61, indicating a high forecast ability. According to the ranking of VIPs from the OPLS-DA models, we found 34 potential metabolic markers with a VIP > 1, and after two pairwise rank sum tests, we found 20 significant potential biomarkers, which were further used in multifactor logistic regressions. Significant substances, including 4-hydroxybenzeneacetic acid (OR=4.74, 95% CI: 1.06-21.06), 5-trimethylsilyloxy-n-valeric acid (OR=15.78, 95% CI: 2.33-106.67), propanedioic acid (OR=5.37, 95% CI: 1.87-15.45), hydracrylic acid (OR=6.23, 95% CI: 1.07-36.21), and uric acid (OR=5.23, 95% CI: 1.23-22.32), were associated with CHD.Conclusion.The major potential biomarkers in maternal urine associated with CHD were 4-hydroxybenzeneacetic acid, 5-trimethylsilyloxy-n-valeric acid, propanedioic acid, hydracrylic acid, and uric acid, respectively. These results indicated that the short chain fatty acids (SCFAs) and aromatic amino acid metabolism may be relevant with CHD.

To explore the prenatal screening and diagnosis for a pair of monochorionic-diamniotic (MCDA) twins discordant for 45,X/46,XX mosaicism.Amniotic fluid samples were taken from both twins for whom non-invasive prenatal testing has signaled a high risk for sex chromosomal abnormality. Uncultured amniotic fluid was analyzed by fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array). Conventional G-banded karyotyping analysis was performed on the cultured amniotic fluid.Metaphase chromosome analysis showed that one of the twins had a mos 45,X[11]/46,XX[26] karyotype, while the other had a normal karyotype. FISH and SNP-array applied on uncultured amniotic fluid revealed about 30% mosaicism in one of the twins. The twins were confirmed to be monozygotic by SNP-array analysis.To avoid confusion arising from discordant karyotypes in MCDA twins with abnormal non-invasive prenatal testing (NIPT) results, dual amniocentesis should be carried out to obtain amniotic fluid samples for chromosomal as well as molecular analysis. To determine the ratio of 45,X and 46,XX cells in Turner syndrome can provide valuable information for prenatal genetic counseling.

Background Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. Objectives We sought to report longer-term tofacitinib efficacy and safety in patients with moderate to severe psoriasis. Methods Data from 2 identical phase-III studies, Oral-treatment Psoriasis Trial Pivotal 1 and 2, were pooled with data from these patients in an ongoing open-label long-term extension study. Patients (n = 1861) were randomized 2:2:1 to tofacitinib 5 mg, 10 mg, or placebo twice daily (BID). At week 16, placebo patients were rerandomized to tofacitinib. Pivotal study participants could enroll into the long-term extension where they received tofacitinib at 10 mg BID for 3 months, after which dosing could be 5 or 10 mg BID. Results At week 28, the proportions of patients randomized to tofacitinib 5 and 10 mg BID achieving 75% or greater reduction in Psoriasis Area and Severity Index score from baseline were 55.6% and 68.8%, and achieving Physician Global Assessment of clear or almost clear were 54.7% and 65.9%. Efficacy was maintained in most patients through 24 months. Serious adverse events and discontinuations because of adverse events were reported in less than 11% of patients over 33 months of tofacitinib exposure. Limitations There was no dose comparison beyond week 52. Conclusions Oral tofacitinib demonstrated sustained efficacy in patients with psoriasis through 2 years, with 10 mg BID providing greater efficacy than 5 mg BID. No unexpected safety findings were observed.