Publications by authors named "Gang Hu"

873 Publications

Accurate estimation of single-cell differentiation potency based on network topology and gene ontology information.

IEEE/ACM Trans Comput Biol Bioinform 2021 Sep 16;PP. Epub 2021 Sep 16.

One important task in the single-cell analysis is to quantify the differentiation potential of single cells. Though various single-cell potency measures have been proposed, they are based on individual biological source, thus not robust and reliable. It is still a challenge to combine multiple sources to generate a relatively reliable and robust measure to estimate differentiation. In this paper, we propose a New Centrality measure with Gene ontology information (NCG) to estimate single-cell potency. NCG is designed by combining network topology property with edge clustering coefficient, and gene function information using gene ontology function similarity scores. NCG distinguishes pluripotent cells from non-pluripotent cells with high accuracy, correctly ranks different cell types by their differentiation potency, tracks changes during the differentiation process, and constructs the lineage trajectory from human myoblasts into skeletal muscle cells. These indicate that NCG is a reliable and robust measure to estimate single-cell potency. NCG is anticipated to be a useful tool for identifying novel stem or progenitor cell phenotypes from single-cell RNA-Seq data. The source codes and datasets are available at https://github.com/Xinzhe-Ni/NCG.
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http://dx.doi.org/10.1109/TCBB.2021.3112951DOI Listing
September 2021

Genetic variants associated with beta-cell function and insulin sensitivity potentially influence bile acid metabolites and gestational diabetes mellitus in a Chinese population.

BMJ Open Diabetes Res Care 2021 Sep;9(1)

School of Public Health (Shenzhen), Sun Yat-Sen University, Shenzhen, Guangdong, China

Introduction: To investigate associations between genetic variants related to beta-cell (BC) dysfunction or insulin resistance (IR) in type 2 diabetes (T2D) and bile acids (BAs), as well as the risk of gestational diabetes mellitus (GDM).

Research Design And Methods: We organized a case-control study of 230 women with GDM and 217 without GDM nested in a large prospective cohort of 22 302 Chinese women in Tianjin, China. Two weighted genetic risk scores (GRSs), namely BC-GRS and IR-GRS, were established by combining 39 and 23 single nucleotide polymorphisms known to be associated with BC dysfunction and IR, respectively. Regression and mediation analyses were performed to evaluate the relationship of GRSs with BAs and GDM.

Results: We found that the BC-GRS was inversely associated with taurodeoxycholic acid (TDCA) after adjustment for confounders (Beta (SE)=-0.177 (0.048); p=2.66×10). The BC-GRS was also associated with the risk of GDM (OR (95% CI): 1.40 (1.10 to 1.77); p0.005), but not mediated by TDCA. Compared with individuals in the low tertile of BC-GRS, the OR for GDM was 2.25 (95% CI 1.26 to 4.01) in the high tertile. An interaction effect of IR-GRS with taurochenodeoxycholic acid (TCDCA) on the risk of GDM was evidenced (p=0.005). Women with high IR-GRS and low concentration of TCDCA had a markedly higher OR of 14.39 (95% CI 1.59 to 130.16; p0.018), compared with those with low IR-GRS and high TCDCA.

Conclusions: Genetic variants related to BC dysfunction and IR in T2D potentially influence BAs at early pregnancy and the development of GDM. The identification of both modifiable and non-modifiable risk factors may facilitate the identification of high-risk individuals to prevent GDM.
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http://dx.doi.org/10.1136/bmjdrc-2021-002287DOI Listing
September 2021

Intrinsic Disorder in Human RNA-binding Proteins.

J Mol Biol 2021 Sep 3:167229. Epub 2021 Sep 3.

Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, USA. Electronic address:

Although RNA-binding proteins (RBPs) are known to be enriched in intrinsic disorder, no previous analysis focused on RBPs interacting with specific RNA types. We fill this gap with a comprehensive analysis of the putative disorder in RBPs binding to six common RNA types: messenger RNA (mRNA), transfer RNA (tRNA), small nuclear RNA (snRNA), non-coding RNA (ncRNA), ribosomal RNA (rRNA), and internal ribosome RNA (irRNA). We also analyze the amount of putative intrinsic disorder in the RNA-binding domains (RBDs) and non-RNA-binding-domain regions (non-RBD regions). Consistent with previous studies, we show that in comparison with human proteome, RBPs are significantly enriched in disorder. However, closer examination finds significant enrichment in predicted disorder for the mRNA-, rRNA- and snRNA-binding proteins, while the proteins that interact with ncRNA and irRNA are not enriched in disorder and the tRNA-binding proteins are significantly depleted in disorder. We show a consistent pattern of significant disorder enrichment in the non-RBD regions coupled with low levels of disorder in RBDs, which suggests that disorder is relatively rarely utilized in the RNA-binding regions. Our analysis of the non-RBD regions suggests that disorder harbors posttranslational modification sites and is involved in the putative interactions with DNA. Importantly, we utilize experimental data from DisProt and independent data from Pfam to validate the above observations that rely on the disorder predictions. This study provides new insights into the distribution of disorder across proteins that bind different RNA types and the functional role of disorder in the regions where it is enriched.
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http://dx.doi.org/10.1016/j.jmb.2021.167229DOI Listing
September 2021

Effect of Two Unique Nanoparticle Formulations on the Efficacy of a Broadly Protective Vaccine Against .

Front Pharmacol 2021 18;12:706157. Epub 2021 Aug 18.

Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, United States.

is an opportunistic pathogen responsible for a wide range of infections in humans. In addition to its innate antibiotic resistance, is very effective in acquiring resistance resulting in the emergence of multi-drug resistance strains and a licensed vaccine is not yet available. We have previously demonstrated the protective efficacy of a novel antigen PaF (Pa Fusion), a fusion of the type III secretion system (T3SS) needle tip protein, PcrV, and the first of two translocator proteins, PopB. PaF was modified to provide a self-adjuvanting activity by fusing the A1 subunit of the heat-labile enterotoxin from Enterotoxigenic to its N-terminus to give L-PaF. In addition to providing protection against 04 and 06 serotypes of , L-PaF elicited opsonophagocytic killing and stimulated IL-17A secretion, which have been predicted to be required for a successful vaccine. While monomeric recombinant subunit vaccines can be protective in mice, this protection often does not transfer to humans where multimeric formulations perform better. Here, we use two unique formulations, an oil-in-water (o/w) emulsion and a chitosan particle, as well as the addition of a unique TLR4 agonist, BECC438 (a detoxified lipid A analogue designated Bacterial Enzymatic Combinatorial Chemistry 438), as an initial step in optimizing L-PaF for use in humans. The o/w emulsion together with BECC438 provided the best protective efficacy, which correlated with high levels of opsonophagocytic killing and IL-17A secretion, thereby reducing the lung burden among all the vaccinated groups tested.
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http://dx.doi.org/10.3389/fphar.2021.706157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416447PMC
August 2021

More vigorous efforts are needed to fight obesity, a serious public health problem in China.

Authors:
Gang Hu

Obesity (Silver Spring) 2021 Aug 31. Epub 2021 Aug 31.

Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.

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http://dx.doi.org/10.1002/oby.23259DOI Listing
August 2021

EXAM: A Framework of Learning Extreme and Moderate Embeddings for Person Re-ID.

J Imaging 2021 Jan 7;7(1). Epub 2021 Jan 7.

Department of Mathematics & Computer and Information Science, Mansfield University of Pennsylvania, Mansfield, PA 16933, USA.

Person re-identification (Re-ID) is challenging due to host of factors: the variety of human positions, difficulties in aligning bounding boxes, and complex backgrounds, among other factors. This paper proposes a new framework called EXAM (EXtreme And Moderate feature embeddings) for Re-ID tasks. This is done using discriminative feature learning, requiring attention-based guidance during training. Here "Extreme" refers to salient human features and "Moderate" refers to common human features. In this framework, these types of embeddings are calculated by global max-pooling and average-pooling operations respectively; and then, jointly supervised by multiple triplet and cross-entropy loss functions. The processes of deducing attention from learned embeddings and discriminative feature learning are incorporated, and benefit from each other in this end-to-end framework. From the comparative experiments and ablation studies, it is shown that the proposed EXAM is effective, and its learned feature representation reaches state-of-the-art performance.
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http://dx.doi.org/10.3390/jimaging7010006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321272PMC
January 2021

Interactions between Prepregnancy Overweight and Passive Smoking for Macrosomia and Large for Gestational Age in Chinese Pregnant Women.

Obes Facts 2021 Aug 20:1-11. Epub 2021 Aug 20.

Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.

Introduction: Previous analysis showed that passive smoking and overweight were associated with an increased risk of gestational diabetes mellitus (GDM) in a synergistic manner, while GDM increased the risk of macrosomia/large for gestational age (LGA). This study aimed to examine any interactive effects between passive smoking and overweight/obesity on risk of macrosomia/LGA.

Methods: From 2010 to 2012, 22,302 pregnant women registered for pregnancy at a primary hospital in Tianjin, China. Data were collected longitudinally; that is, from their first antenatal care visit, at the glucose challenge test (GCT) time (24-28 weeks of gestation) and at delivery. Passive smoking was self-reported. Macrosomia was defined as birth weight ≥4,000 g. Binary logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction was used to test the synergistic effect.

Results: Passive smokers accounted for 57.4% of women (n = 8,230). Using nonpassive smoking and prepregnancy body mass index (BMI) <24.0 kg/m2 as the reference, the adjusted ORs of overweight alone and passive smoking alone for macrosomia were 2.39 (95% CI: 2.11-2.71) and 1.17 (95% CI: 1.04-1.32). Copresence of passive smoking and prepregnancy BMI ≥24.0 kg/m2 increased the OR to 2.70 (95% CI: 2.28-3.20), with a significant additive interaction. After further adjustment for GDM or GCT, the OR of copresence of both risk factors was slightly attenuated to 2.52 (2.13-3.00) and 2.51 (2.11-2.98), with significant additive interaction. However, the additive interaction between prepregnancy overweight/obesity and passive smoking for LGA was nonsignificant.

Conclusions: Prepregnancy overweight/obesity was associated with an increased risk of macrosomia in Chinese women synergistically with passive smoking during pregnancy, and most of the association was not modified by hyperglycemia during pregnancy.
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http://dx.doi.org/10.1159/000517846DOI Listing
August 2021

Cardiovascular Risk Factor Status in Hospitalized Patients With Type 2 Diabetes in China.

Front Endocrinol (Lausanne) 2021 22;12:664183. Epub 2021 Jul 22.

Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

Background: Controlling blood glucose, blood pressure, and blood lipid is of great importance for patients with type 2 diabetes, not only for cardiovascular disease, but also for other complications. Previous studies mainly focused on the control rate of outpatients, and the results were suboptimal, but few studies aimed at the inpatients.

Method: The present study involved 3,245 hospitalized patients with type 2 diabetes from 2013 to 2017 in the Department of Endocrinology and Metabolism of Tianjin Medical University General Hospital. The percentages of inpatients who attained the goals of the China Diabetes Society and the American Diabetes Association were calculated for major cardiovascular risk factors (HbA1c, blood pressure, and blood lipid). The prevalence of microvascular and macrovascular complications was also assessed.

Result: The percentages of patients who met the Chinese Diabetes Society goals-HbA1c <7%, blood pressure <130/80 mmHg, normal lipids, and all three goals-were 26.7, 14.8, 10.4, and 0.2% in 2013 and 30.5, 16.2, 8.0, and 0.9% in 2017, respectively. The percentage of patients who met all three American Diabetes Association goals (HbA1c<7%, blood pressure <140/90 mmHg, low-density lipoprotein cholesterol <2.6 mmol/L) increased from 4.3% in 2013 to 9.0% in 2017. The prevalence of major diabetes complications including coronary heart disease (31.7 . 31.9%), stroke (16.7 . 14.8%), diabetic kidney disease (37.9 . 35.8%), diabetic retinopathy (48.0 . 46.5%), neuropathy (63.1 . 61.9%), and diabetic foot (0.8 . 1.2%) were stable from 2013 to 2017.

Conclusion: During 2013 to 2017, control rates of major cardiovascular risk factors including HbA1c, blood pressure, and low-density lipoprotein cholesterol were improved among hospitalized patients in Tianjin, China.
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http://dx.doi.org/10.3389/fendo.2021.664183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339370PMC
July 2021

Novel epigenetic link between gestational diabetes mellitus and macrosomia.

Epigenomics 2021 Aug 2;13(15):1221-1230. Epub 2021 Aug 2.

Center for Global Oncology, Institute for Global Health, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Examine maternal gestational diabetes mellitus (GDM), macrosomia and DNA methylation in candidate genes , , , , , ,  and . A total of 1145 children (572 GDM cases and 573 controls) from the Tianjin GDM study, including 177 with macrosomia, had blood DNA collection at median age 5.9 (range: 3.1-10.0). We used logistic regression to screen for associations with GDM and model macrosomia on 37 CpGs, and performed mediation analysis. One CpG was associated with macrosomia at false discovery rate (FDR) <0.05 (cg14428359 in ); two (cg19466922 in and cg26263166 in ) were associated at p < 0.05 but mediated 26 and 13%, respectively. and were previously identified for potential involvement in fetal growth and development (Trial Registration number: NCT01554358 [ClinicalTrials.gov]).
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http://dx.doi.org/10.2217/epi-2021-0096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371577PMC
August 2021

Effective Treatment Recommendations for Type 2 Diabetes Management Using Reinforcement Learning: Treatment Recommendation Model Development and Validation.

J Med Internet Res 2021 Jul 22;23(7):e27858. Epub 2021 Jul 22.

Ping An Healthcare Technology, Beijing, China.

Background: Type 2 diabetes mellitus (T2DM) and its related complications represent a growing economic burden for many countries and health systems. Diabetes complications can be prevented through better disease control, but there is a large gap between the recommended treatment and the treatment that patients actually receive. The treatment of T2DM can be challenging because of different comprehensive therapeutic targets and individual variability of the patients, leading to the need for precise, personalized treatment.

Objective: The aim of this study was to develop treatment recommendation models for T2DM based on deep reinforcement learning. A retrospective analysis was then performed to evaluate the reliability and effectiveness of the models.

Methods: The data used in our study were collected from the Singapore Health Services Diabetes Registry, encompassing 189,520 patients with T2DM, including 6,407,958 outpatient visits from 2013 to 2018. The treatment recommendation model was built based on 80% of the dataset and its effectiveness was evaluated with the remaining 20% of data. Three treatment recommendation models were developed for antiglycemic, antihypertensive, and lipid-lowering treatments by combining a knowledge-driven model and a data-driven model. The knowledge-driven model, based on clinical guidelines and expert experiences, was first applied to select the candidate medications. The data-driven model, based on deep reinforcement learning, was used to rank the candidates according to the expected clinical outcomes. To evaluate the models, short-term outcomes were compared between the model-concordant treatments and the model-nonconcordant treatments with confounder adjustment by stratification, propensity score weighting, and multivariate regression. For long-term outcomes, model-concordant rates were included as independent variables to evaluate if the combined antiglycemic, antihypertensive, and lipid-lowering treatments had a positive impact on reduction of long-term complication occurrence or death at the patient level via multivariate logistic regression.

Results: The test data consisted of 36,993 patients for evaluating the effectiveness of the three treatment recommendation models. In 43.3% of patient visits, the antiglycemic medications recommended by the model were concordant with the actual prescriptions of the physicians. The concordant rates for antihypertensive medications and lipid-lowering medications were 51.3% and 58.9%, respectively. The evaluation results also showed that model-concordant treatments were associated with better glycemic control (odds ratio [OR] 1.73, 95% CI 1.69-1.76), blood pressure control (OR 1.26, 95% CI, 1.23-1.29), and blood lipids control (OR 1.28, 95% CI 1.22-1.35). We also found that patients with more model-concordant treatments were associated with a lower risk of diabetes complications (including 3 macrovascular and 2 microvascular complications) and death, suggesting that the models have the potential of achieving better outcomes in the long term.

Conclusions: Comprehensive management by combining knowledge-driven and data-driven models has good potential to help physicians improve the clinical outcomes of patients with T2DM; achieving good control on blood glucose, blood pressure, and blood lipids; and reducing the risk of diabetes complications in the long term.
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http://dx.doi.org/10.2196/27858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367185PMC
July 2021

flDPnn: Accurate intrinsic disorder prediction with putative propensities of disorder functions.

Nat Commun 2021 07 21;12(1):4438. Epub 2021 Jul 21.

Department of Computer Science, Virginia Commonwealth University, Richmond, VA, USA.

Identification of intrinsic disorder in proteins relies in large part on computational predictors, which demands that their accuracy should be high. Since intrinsic disorder carries out a broad range of cellular functions, it is desirable to couple the disorder and disorder function predictions. We report a computational tool, flDPnn, that provides accurate, fast and comprehensive disorder and disorder function predictions from protein sequences. The recent Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment and results on other test datasets demonstrate that flDPnn offers accurate predictions of disorder, fully disordered proteins and four common disorder functions. These predictions are substantially better than the results of the existing disorder predictors and methods that predict functions of disorder. Ablation tests reveal that the high predictive performance stems from innovative ways used in flDPnn to derive sequence profiles and encode inputs. flDPnn's webserver is available at http://biomine.cs.vcu.edu/servers/flDPnn/.
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http://dx.doi.org/10.1038/s41467-021-24773-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295265PMC
July 2021

Association of HbA1c with all-cause mortality across varying degrees of glycemic variability in type 2 diabetes.

J Clin Endocrinol Metab 2021 Jul 19. Epub 2021 Jul 19.

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.

Context: The interaction of glycated hemoglobin A1c (HbA1c) and glycemic variability in relation to diabetes-related outcomes remains unknown.

Objective: To evaluate the relationship between HbA1c and all-cause mortality across varying degrees of glycemic variability in patients with type 2 diabetes.

Design, Setting, And Patients: This was a prospective study conducted in a single referral center. Data of 6090 hospitalized patients with type 2 diabetes was analyzed. Glucose coefficient of variation (CV) was obtained as the measure of glycemic variability by using continuous glucose monitoring (CGM) for 3 days. Cox proportional hazards regression models were used to estimate hazard ratios and 95% CIs for all-cause mortality.

Results: During a median follow-up of 6.8 years, 815 patients died. In patients with the lowest and middle tertiles of glucose CV, HbA1c ≥8.0% was associated with 136% (95%CI 1.46-3.81) and 92% (95%CI 1.22-3.03) higher risks of all-cause mortality as compared with HbA1c 6.0-6.9%, respectively, after adjusting for confounders. However, a null association of HbA1c with mortality was found in patients with the highest tertile of glucose CV.

Conclusions: HbA1c may not be a robust marker of all-cause mortality in patients with high degree of glycemic variability. New metrics of glycemic control may be needed in these individuals to achieve better diabetes management.
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http://dx.doi.org/10.1210/clinem/dgab532DOI Listing
July 2021

Identification and validation of a novel ferroptosis-related gene model for predicting the prognosis of gastric cancer patients.

PLoS One 2021 12;16(7):e0254368. Epub 2021 Jul 12.

Department of Pathology, Huangshi Central Hospital of Edong Healthcare Group, Hubei Polytechnic University, Huangshi, Hubei, China.

Background: Ferroptosis is a novel form of regulated cell death that plays a critical role in tumorigenesis. The purpose of this study was to establish a ferroptosis-associated gene (FRG) signature and assess its clinical outcome in gastric cancer (GC).

Methods: Differentially expressed FRGs were identified using gene expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were performed to construct a prognostic signature. The model was validated using an independent GEO dataset, and a genomic-clinicopathologic nomogram integrating risk scores and clinicopathological features was established.

Results: An 8-FRG signature was constructed to calculate the risk score and classify GC patients into two risk groups (high- and low-risk) according to the median value of the risk score. The signature showed a robust predictive capacity in the stratification analysis. A high-risk score was associated with advanced clinicopathological features and an unfavorable prognosis. The predictive accuracy of the signature was confirmed using an independent GSE84437 dataset. Patients in the two groups showed different enrichment of immune cells and immune-related pathways. Finally, we established a genomic-clinicopathologic nomogram (based on risk score, age, and tumor stage) to predict the overall survival (OS) of GC patients.

Conclusions: The novel FRG signature may be a reliable tool for assisting clinicians in predicting the OS of GC patients and may facilitate personalized treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254368PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274920PMC
July 2021

Ultrahigh sensitive transient absorption spectrometer.

Rev Sci Instrum 2021 May;92(5):053002

State Key Laboratory of Molecular Reaction Dynamics and Dynamics Research Center for Energy and Environmental Materials, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

Transient absorption (TA) spectroscopy is considered as a powerful technique that reflects the ultrafast dynamics of photogenerated carriers in photoelectric and photocatalysis materials. However, limited by its sensitivity, the photogenerated carrier density in TA measurements of solar energy materials is usually much higher than that in the real working condition. Here, we present a combination of kHz macro-pulse and MHz micro-pulse technique for an ultrahigh sensitive TA spectrometer, which improves the sensitivity to the 10 level of ΔOD. It enables us to study ultrafast carrier dynamics pumped by very low power, which can avoid the influence of many-body interactions and the nonlinear effect associated with high carrier density. This work provides a novel TA method with ultrahigh sensitivity, which will play an important role in investigating the carrier dynamics of semiconductors in the working condition.
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http://dx.doi.org/10.1063/5.0048115DOI Listing
May 2021

Serum uric acid and its change with the risk of type 2 diabetes: A prospective study in China.

Prim Care Diabetes 2021 Jun 30. Epub 2021 Jun 30.

Department of Health Management, Tianjin Medical University General Hospital, Tianjin, China. Electronic address:

Objective: To assess the association of baseline uric acid levels and their changes from baseline to Year 1 with the risk of type 2 diabetes.

Research Design And Methods: This study cohort included 9471 subjects without a history of diabetes at baseline. The incident diabetes was diagnosed according to the American Diabetes Association standard.

Results: During a mean follow-up of 2.9 years, we identified 762 type 2 diabetes cases. Multivariate-adjusted hazard ratios (HRs) of diabetes across baseline tertiles of serum uric acid were 1.00, 1.15, and 1.32 (P for trend = 0.018), respectively. Participants with hyperuricemia compared with those without had a 1.20-fold (95% confidence interval [CI] 1.01-1.44) risk of diabetes. When uric acid was examined as a continuous variable, multivariable-adjusted HR of diabetes for each 1 mg/dL (60 μmol/L) increase in serum uric acid was 1.09 (95% CI 1.03-1.15). Compared with subjects with stable serum uric acid from baseline to Year 1 (±10%), those with uric acid gain ≥30% had a 30% (95% CI 1.01-1.79) increased risk of diabetes and those with uric acid loss ≥10% had a 21% (95% 0.62-0.99) decreased risk of diabetes. This positive association between baseline serum uric acid and diabetes risk was consistent among subjects younger and older than 45 years, non-obese and obese participants, and men.

Conclusions: High level of baseline serum uric acid and serum uric acid gain from baseline to Year 1 are associated with an increased risk of type 2 diabetes among Chinese adults.
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http://dx.doi.org/10.1016/j.pcd.2021.06.010DOI Listing
June 2021

Prediction of skin disease using a new cytological taxonomy based on cytology and pathology with deep residual learning method.

Sci Rep 2021 Jul 2;11(1):13764. Epub 2021 Jul 2.

Sino-French Hoffmann Institute, School of Basic Sciences, The Second Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, 511436, Guangdong, China.

With the development of artificial intelligence, technique improvement of the classification of skin disease is addressed. However, few study concerned on the current classification system of International Classification of Diseases, Tenth Revision (ICD)-10 on Diseases of the skin and subcutaneous tissue, which is now globally used for classification of skin disease. This study was aimed to develop a new taxonomy of skin disease based on cytology and pathology, and test its predictive effect on skin disease compared to ICD-10. A new taxonomy (Taxonomy 2) containing 6 levels (Project 2-4) was developed based on skin cytology and pathology, and represents individual diseases arranged in a tree structure with three root nodes representing: (1) Keratinogenic diseases, (2) Melanogenic diseases, and (3) Diseases related to non-keratinocytes and non-melanocytes. The predictive effects of the new taxonomy including accuracy, precision, recall, F1, and Kappa were compared with those of ICD-10 on Diseases of the skin and subcutaneous tissue (Taxonomy 1, Project 1) by Deep Residual Learning method. For each project, 2/3 of the images were included as training group, and the rest 1/3 of the images acted as test group according to the category (class) as the stratification variable. Both train and test groups in the Projects (2 and 3) from Taxonomy 2 had higher F1 and Kappa scores without statistical significance on the prediction of skin disease than the corresponding groups in the Project 1 from Taxonomy 1, however both train and test groups in Project 4 had a statistically significantly higher F1-score than the corresponding groups in Project 1 (P = 0.025 and 0.005, respectively). The results showed that the new taxonomy developed based on cytology and pathology has an overall better performance on predictive effect of skin disease than the ICD-10 on Diseases of the skin and subcutaneous tissue. The level 5 (Project 4) of Taxonomy 2 is better on extension to unknown data of diagnosis system assisted by AI compared to current used classification system from ICD-10, and may have the potential application value in clinic of dermatology.
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http://dx.doi.org/10.1038/s41598-021-92848-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253798PMC
July 2021

Serum concentrations of SFAs and CDKAL1 single-nucleotide polymorphism rs7747752 are related to an increased risk of gestational diabetes mellitus.

Am J Clin Nutr 2021 Jun 30. Epub 2021 Jun 30.

Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.

Background: Interactions between genetic and nutritional factors can contribute to the risk of gestational diabetes mellitus (GDM).

Objectives: We aimed to explore the associations of cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1 (CDKAL1) single-nucleotide polymorphism (SNP) rs7747752 and serum concentrations of SFAs with the risk of GDM in Chinese women.

Methods: We conducted a 1:1 case-control study in a prospective cohort of pregnant women in Tianjin, China. Serum SFA data were collected from a total of 243 women with GDM and their controls matched by maternal age (±1 y). Among them, 207 case-control pairs had high-quality sequencing data. P/L and S/P ratios were defined as palmitic acid (16:0)/lauric acid (12:0) and stearic acid (18:0)/palmitic acid, respectively. Conditional logistic regression analysis was performed to estimate associations of CDKAL1 SNP rs7747752 and serum concentrations of SFAs with the risk of GDM. An additive interaction between rs7747752 and palmitic acid was analyzed to test the contribution of their interaction to the risk of GDM.

Results: Among the 5 tested SFAs, palmitic acid was positively whereas lauric acid was negatively associated with the risk of GDM. A P/L ratio ≥12.2 and an S/P ratio ≤0.71 were independently and synergistically associated with an increased risk of GDM. The CDKAL1 rs7747752 G > C variant was significantly associated with an increased risk of GDM (P < 0.05). Furthermore, the presence of the rs7747752 G > C variant increased the OR (95% CI) of high palmitic acid concentration from 1.55 (0.61, 3.97) to 4.34 (2.04, 9.23), with a significant additive interaction.

Conclusions: The interaction between high serum palmitic acid concentration and the CDKAL1 rs7747752 G > C variant played a critical role in GDM. Given that a hypocaloric low-carbohydrate diet can lower palmitic acid concentrations, it is worthwhile to test whether such a diet is effective in reducing the risk of GDM, especially among women who have both risk factors.
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http://dx.doi.org/10.1093/ajcn/nqab225DOI Listing
June 2021

Acautalides A-C, Neuroprotective Diels-Alder Adducts from Solid-State Cultivated sp. H-JQSF.

Org Lett 2021 Jul 30;23(14):5587-5591. Epub 2021 Jun 30.

State Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional Biomolecules, Nanjing University, Nanjing, Jiangsu 210023, People's Republic of China.

The solid-state cultivation of sp. H-JQSF isolated from produces acautalides A-C (-) as skeletally unprecedented Diels-Alder adducts of a 14-membered macrodiolide to an octadeca-9,11,13-trienoic acid. The acautalide structures, along with the intramolecular transesterifications of 1-acylglycerols, were elucidated by mass spectrometry, nuclear magnetic resonance, chemical transformation, and single-crystal X-ray diffraction. Compounds - were found to be neuroprotective with antiparkinsonic potential in the 1-methyl-4-phenylpyridinium-challenged nematode model, with the magnitude impacted by the glycerol esterification.
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http://dx.doi.org/10.1021/acs.orglett.1c02089DOI Listing
July 2021

Association between visit-to-visit variability of glycated albumin and diabetic retinopathy among patients with type 2 diabetes - A prospective cohort study.

J Diabetes Complications 2021 Sep 29;35(9):107971. Epub 2021 May 29.

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, China. Electronic address:

Aim: There is a paucity of studies regarding the association between long-term glycemic variability with the risk of diabetic retinopathy (DR) in patients with type 2 diabetes. Therefore, the purpose of this study is to explore the association of glycated albumin (GA) variability and HbA1c variability with the risk of DR in patients with type 2 diabetes.

Methods: This prospective cohort study included 315 inpatients with type 2 diabetes (191 males and 124 females) with at least 3 measurements of GA and HbA1c within 2years prior to the baseline investigation. Different GA and HbA1c variability markers were calculated, including CV, variability independent of the mean (VIM), and the average real variability (ARV). Cox proportional hazard regression models were used to explore the association between visit-to-visit variability of GA and HbA1c and the risk of DR.

Results: After an average follow-up of 3.42years, 81 patients developed incident DR. Multivariable-adjusted (diabetes duration, smoking status, systolic blood pressure, albumin to creatinine ratio, triglycerides, using fibrates, and mean HbA1c) hazard ratios of DR associated with each unit increase in GA-CV, GA-VIM, and GA-ARV were 1.05 (95% CI 1.02-1.09), 1.69 (95% CI 1.24-2.32), and 1.13 (95%CI 1.04-1.23), respectively. However, there was no significant association between visit-to-visit HbA1c variability and the risk of DR.

Conclusions: The present study indicated that visit-to-visit variability of GA can predict the risk of incident DR in patients with type 2 diabetes, and the prediction ability is independent of the average HbA1c levels.
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http://dx.doi.org/10.1016/j.jdiacomp.2021.107971DOI Listing
September 2021

Circular RNA circRHOBTB3 is downregulated in hepatocellular carcinoma and suppresses cell proliferation by inhibiting miR-18a maturation.

Infect Agent Cancer 2021 Jun 29;16(1):48. Epub 2021 Jun 29.

Department of General Surgery, Strategic Support Force Characteristic Medical Center, Beijing, 100101, People's Republic of China.

Background: Circular RNA circRHOBTB3 has been characterized as a tumor suppressor in gastric cancer, while its role in hepatocellular carcinoma (HCC) is unknown. This study was carried out to analyze the role of circRHOBTB3 in HCC.

Methods: In this study, circRHOBTB3, mature miR-18a, and miR-18a precursor in HCC and paired non-cancer tissues were detected by RT-qPCR. The role of circRHOBTB3 in the production of mature miR-18a was explored by transfecting circRHOBTB3 expression vector into HCC cells, followed by RT-qPCR to determine the expression of mature miR-18a and miR-18a precursor. The role of circRHOBTB3 and miR-18a in HCC cell proliferation was studied using CCK-8 assay.

Results: CircRHOBTB3 was under-expressed in HCC compared to normal tissues. In HCC cells, circRHOBTB3 overexpression decreased mature miR-18a level but not miR-18a precursor. Cell proliferation analysis showed that circRHOBTB3 overexpression decreased cell proliferation while miR-18a overexpression increased cell proliferation. Moreover, circRHOBTB3 suppressed the role of miR-18a in cell proliferation.

Conclusions: CircRHOBTB3 is downregulated in HCC and may suppress cell proliferation by reducing miR-18a production.
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http://dx.doi.org/10.1186/s13027-021-00384-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243428PMC
June 2021

Complete chloroplast genome of a semi-mangrove plant (Malvaceae).

Mitochondrial DNA B Resour 2021 Jun 14;6(7):1904-1905. Epub 2021 Jun 14.

College of Environmental and Life Sciences, Nanning Normal University, Nanning, China.

is a semi-mangrove species that is widely distributed in tropical and subtropical coastal areas around the world. Here, the complete chloroplast (cp) genome sequence of was assembled and characterized. The cp genome was 161,748 bp in length, consisting of a large single copy (LSC) region of 89,190 bp and a small single copy (SSC) region of 19,616 bp, which were separated by a pair of 26,471 bp inverted repeat (IR) regions. The overall GC content was 36.88%. A total of 131 genes, including 85 protein-coding genes, 37 tRNA genes and 8 rRNA genes were identified. Phylogenetic tree reconstructed by 15 complete cp genomes revealed that was sister to the congeneric species .
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http://dx.doi.org/10.1080/23802359.2021.1935337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204996PMC
June 2021

Calcium Positively Mediates Blue Light-Induced Anthocyanin Accumulation in Hypocotyl of Soybean Sprouts.

Front Plant Sci 2021 28;12:662091. Epub 2021 May 28.

College of Life Sciences, Nanjing Agricultural University, Nanjing, China.

Soybean sprouts are a flavorful microgreen that can be eaten all year round and are widely favored in Southeast Asia. In this study, the regulatory mechanism of calcium on anthocyanin biosynthesis in soybean sprouts under blue light was investigated. The results showed that blue light, with a short wavelength, effectively induced anthocyanin accumulation in the hypocotyl of soybean sprout cultivar "Dongnong 690." Calcium supplementation further enhanced anthocyanin content, which was obviously inhibited by LaCl and neomycin treatment. Moreover, exogenous calcium changed the metabolism of anthocyanins, and seven anthocyanin compounds were detected. The trend of calcium fluorescence intensity in hypocotyl cells, as well as that of the inositol 1,4,5-trisphosphate and calmodulin content, was consistent with that of anthocyanins content. Specific spatial distribution patterns of calcium antimonate precipitation were observed in the ultrastructure of hypocotyl cells under different conditions. Furthermore, calcium application upregulated the expression of genes related to anthocyanin biosynthesis, and calcium inhibitors suppressed these genes. Finally, transcriptomics was performed to gain global insights into the molecular regulation mechanism of calcium-associated anthocyanin production. Genes from the flavonoid biosynthesis pathway were distinctly enriched among the differentially expressed genes, and weighted gene co-expression network analysis showed that two MYBs were related to the accumulation of anthocyanins. These results indicated that calcium released from apoplast and intracellular stores in specific spatial-temporal features promote blue light-induced anthocyanin accumulation by upregulation of the expression of genes related to anthocyanin synthesis of "Dongnong 690" hypocotyl. The findings deepen the understanding of the calcium regulation mechanism of blue light-induced anthocyanin accumulation in soybean sprouts, which will help growers produce high-quality foods beneficial for human health.
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http://dx.doi.org/10.3389/fpls.2021.662091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194075PMC
May 2021

Quercetin hinders microglial activation to alleviate neurotoxicity via the interplay between NLRP3 inflammasome and mitophagy.

Redox Biol 2021 08 25;44:102010. Epub 2021 May 25.

Department of Rheumatology and Immunology, Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China. Electronic address:

Activated microglia are an important type of innate immune cell in the brain, and they secrete inflammatory cytokines into the extracellular milieu, exert neurotoxicity to surrounding neurons and are involved in the pathogenesis of many brain disorders. Quercetin (Qu), a natural flavonoid, is known to have anti-inflammatory and antioxidant properties. Previous studies have shown that both increased reactive oxygen species (ROS) stress and decreased autophagy participate in the activation of microglial. In the current study, we showed that Qu significantly attenuated LPS-induced inflammatory factor production, cell proliferation and NF-κB activation of microglia. Importantly, Qu decreased the levels of NLR family, pyrin domain containing three (NLRP3) inflammasome and pyroptosis-related proteins, including NLRP3, active caspase-1, GSDMD N-terminus and cleaved IL-1β. Further study indicated that this anti-inflammatory effect of Qu was associated with mitophagy regulation. Importantly, Qu promoted mitophagy to enhance damaged mitochondrial elimination, which then reduced mtROS accumulation and alleviated NLRP3 inflammasome activation. Then, we confirmed that Qu treatment protected primary neurons against LPS-induced microglial toxicity and alleviated neurodegeneration in both depression and PD mouse models. Further IL-1β administration blunted these neuroprotective effects of Qu in vitro and in vivo. This work illustrated that Qu prevents neuronal injury via inhibition of mtROS-mediated NLRP3 inflammasome activation in microglia through promoting mitophagy, which provides a potential novel therapeutic strategy for neuroinflammation-related diseases.
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http://dx.doi.org/10.1016/j.redox.2021.102010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182123PMC
August 2021

Physical activity and sleep duration during pregnancy have interactive effects on caesarean delivery: a population-based cohort study in Tianjin, China.

BMC Pregnancy Childbirth 2021 May 28;21(1):406. Epub 2021 May 28.

Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, P.O. Box 154, 22 Qixiangtai Road, Heping District, Tianjin 300070, China.

Background: There were inconsistent findings in the literature regarding the associations of physical activity and sleep duration during pregnancy with caesarean delivery for different reasons. It was also unknown whether physical activity and sleep duration during pregnancy had interactive effects on the risks of different types of caesarean delivery. The study aimed to investigate the effects of physical activity, sleep duration and their interactions on the risk of caesarean delivery for medical reasons and non-medical reasons.

Methods: From October 2010 to August 2012, a prospective population-based cohort of 13,015 pregnant women was established in six central urban districts of Tianjin, China. Pregnancy outcomes were retrieved from an electronic database and caesarean delivery was divided into caesarean delivery for medical reasons and caesarean delivery for non-medical reasons. Physical activity and sleep status were collected at 24-28 weeks of gestation using self-reported questionnaires. Logistic regression and additive interaction were used to examine physical activity, sleep duration and their interactive effects on risk of caesarean delivery.

Results: In the cohort, 5692 (43.7%) and 2641 (20.3%) of women had caesarean delivery for medical reasons and non-medical reasons, respectively. Low physical activity increased the risk of caesarean delivery for medical reasons (adjusted OR: 1.13, 95%CI 1.04-1.23) but not caesarean delivery for non-medical reasons. Sleep duration < 7 h/day and poor sleep quality were not associated with caesarean delivery. Sleep duration ≥9 h/day increased the risk of caesarean delivery for medical reasons (1.12, 1.02-1.22) and caesarean delivery for non-medical reasons (1.16, 1.05-1.29). Co-presence of low physical activity and sleep duration ≥9 h/day increased risk of caesarean delivery (1.25, 1.12-1.41), and their additive interaction was statistically significant for caesarean delivery for medical reasons but not for caesarean delivery for non-medical reasons.

Conclusions: Low physical activity and excessive sleep duration during pregnancy each increased the risk of caesarean delivery, and they had an interactive effect on the risk of caesarean delivery for medical reasons but not on the risk of caesarean delivery for non-medical reasons. Increasing physical activity and maintaining recommended sleep duration during pregnancy may have benefits for perinatal health.
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http://dx.doi.org/10.1186/s12884-021-03788-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161996PMC
May 2021

A joint deep learning model enables simultaneous batch effect correction, denoising, and clustering in single-cell transcriptomics.

Genome Res 2021 May 25. Epub 2021 May 25.

Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Recent developments of single-cell RNA-seq (scRNA-seq) technologies have led to enormous biological discoveries. As the scale of scRNA-seq studies increases, a major challenge in analysis is batch effects, which are inevitable in studies involving human tissues. Most existing methods remove batch effects in a low-dimensional embedding space. Although useful for clustering, batch effects are still present in the gene expression space, leaving downstream gene-level analysis susceptible to batch effects. Recent studies have shown that batch effect correction in the gene expression space is much harder than in the embedding space. Methods such as Seurat 3.0 rely on the mutual nearest neighbor (MNN) approach to remove batch effects in gene expression, but MNN can only analyze two batches at a time, and it becomes computationally infeasible when the number of batches is large. Here, we present CarDEC, a joint deep learning model that simultaneously clusters and denoises scRNA-seq data while correcting batch effects both in the embedding and the gene expression space. Comprehensive evaluations spanning different species and tissues showed that CarDEC outperforms Scanorama, DCA + Combat, scVI, and MNN. With CarDEC denoising, non-highly variable genes offer as much signal for clustering as the highly variable genes (HVGs), suggesting that CarDEC substantially boosted information content in scRNA-seq. We also showed that trajectory analysis using CarDEC's denoised and batch-corrected expression as input revealed marker genes and transcription factors that are otherwise obscured in the presence of batch effects. CarDEC is computationally fast, making it a desirable tool for large-scale scRNA-seq studies.
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http://dx.doi.org/10.1101/gr.271874.120DOI Listing
May 2021

QUARTERplus: Accurate disorder predictions integrated with interpretable residue-level quality assessment scores.

Comput Struct Biotechnol J 2021 27;19:2597-2606. Epub 2021 Apr 27.

Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, USA.

A recent advance in the disorder prediction field is the development of the quality assessment (QA) scores. QA scores complement the propensities produced by the disorder predictors by identifying regions where these predictions are more likely to be correct. We develop, empirically test and release a new QA tool, QUARTERplus, that addresses several key drawbacks of the current QA method, QUARTER. QUARTERplus is the first solution that utilizes QA scores and the associated input disorder predictions to produce very accurate disorder predictions with the help of a modern deep learning meta-model. The deep neural network utilizes the QA scores to identify and fix the regions where the original/input disorder predictions are poor. More importantly, the accurate QUATERplus's predictions are accompanied by easy to interpret residue-level QA scores that reliably quantify their residue-level predictive quality. We provide these interpretable QA scores for QUARTERplus and 10 other popular disorder predictors. Empirical tests on a large and independent (low similarity) test dataset show that QUARTERplus predictions secure AUC = 0.93 and are statistically more accurate than the results of twelve state-of-the-art disorder predictors. We also demonstrate that the new QA scores produced by QUARTERplus are highly correlated with the actual predictive quality and that they can be effectively used to identify regions of correct disorder predictions. This feature empowers the users to easily identify which parts of the predictions generated by the modern disorder predictors are more trustworthy. QUARTERplus is available as a convenient webserver at http://biomine.cs.vcu.edu/servers/QUARTERplus/.
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http://dx.doi.org/10.1016/j.csbj.2021.04.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122155PMC
April 2021

Brain structural plasticity in visual and sensorimotor areas of airline pilots: A voxel-based morphometric study.

Behav Brain Res 2021 Aug 21;411:113377. Epub 2021 May 21.

Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing, 100850, China. Electronic address:

Background And Purpose: Airline pilot is a highly specialized profession that requires to response quickly and accurately in the presence of a wide variety of visual information. Although functional imaging studies have employed virtual simulation to identify brain areas that underlie various flying-related tasks, little is known about the specific patterns of structural plasticity in the airline pilot's brain.

Materials And Methods: In this study, we examined differences of gray matter and white matter volumes between 42 airline pilots and 39 non-pilots by using voxel-based morphometry, and further assessed the association between magnitude of structural alterations and flight time in the pilots.

Results: We found significantly increased white matter volume in the cuneus area in the pilot group compared to the non-pilot group (p <  0.05, FWE corrected). Using a relaxed threshold, it was also observed that the pilots had increased gray matter volume in the lingual gyrus, inferior frontal gyrus, supramarginal gyrus, cuneus, and postcentral gyrus, and increased white matter volume in the postcentral area (p <  0.001, uncorrected). Moreover, the pilots' flight time was positively correlated with gray matter volume in the postcentral gyrus and white matter volume in the cuneus area (p <  0.001, uncorrected).

Conclusions: The morphological changes in specific visual and sensorimotor areas may provide airline pilots with neural efficiency in the visuo-motor processing related to flight.
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http://dx.doi.org/10.1016/j.bbr.2021.113377DOI Listing
August 2021

Maternal gestational diabetes and childhood hyperlipidemia.

Diabet Med 2021 May 22:e14606. Epub 2021 May 22.

Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.

Aims: Aim of this study is to assess dyslipidemia risk between children exposed to maternal gestational diabetes mellitus (GDM) and those not exposed.

Methods: We recruited 1144 mother-child pairs (572 GDM and 572 non-GDM women matched by their offspring's age and sex). The age of offspring ranged from 3 to 9 years old. We used general linear models to compare mean values of different lipid profiles among children born to mothers with and without GDM. Logistic regression models were used to assess associations of maternal GDM with abnormal lipid profiles in offspring.

Results: After adjustment for maternal and children's characteristics, children born to mothers with GDM had lower mean values of high-density-lipoprotein (HDL) cholesterol (1.40 ± 0.01 vs. 1.50 ± 0.01; p < 0.001) and higher mean levels of triglycerides/HDL cholesterol ratio (0.37 ± 0.01 vs. 0.35 ± 0.01; p < 0.05) in comparison with their counterparts born to mothers without GDM. Multivariate-adjusted odds ratios among children exposed to mothers with GDM compared with the counterparts were 2.11 (95% confidence interval [CI 1.15-3.88]) for low HDL cholesterol and 1.35 (95% CI 1.00-1.81) for high triglycerides/HDL cholesterol ratio, respectively.

Conclusions: Maternal GDM was associated with an increased risk of hyperlipidemia in the offspring during early childhood aged from 3 to 9 years old.
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http://dx.doi.org/10.1111/dme.14606DOI Listing
May 2021

Novel deep intronic and frameshift mutations causing a TRIP11-related disorder.

Am J Med Genet A 2021 08 20;185(8):2482-2487. Epub 2021 May 20.

Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, China.

Mutations of the thyroid hormone receptor interactor 11 gene (TRIP11, OMIM: 604505) at 14q32.12 have been associated with the autosomal recessive achondrogenesis type IA (ACG1A, OMIM: 200600) or osteochondrodysplasia (ODCD, OMIM: 184260). In this clinical report of a Chinese family, the mother had two consecutive pregnancies with similar aberrant phenotypes in the fetuses showing severe limb shortening. Whole exome sequencing (WES) of DNA from the second fetus identified a heterozygous frameshift mutation (NM_004239: c.3852delT) of TRIP11. Although this was consistent with the fetal clinical phenotypes, initial review of the WES results implied another novel mutation. To test this, we used high-precision clinical exome sequencing (HPCES) and found a mutation in Intron 18 of TRIP11 (c.5457+77T>G). Moreover, the sequencing depth of this mutation was only 3× that of WES compared with 161× that by HPCES. To ascertain the pathogenesis of the mutation (c.5457+77T>G), RT-PCR conducted using the parents' blood samples showed a 77-bp intronic sequence in the transcripts, which might have encoded for a shortened protein because of early termination due to code shifting. Our study furthers current understanding of deep intron function and provides a novel diagnostic method of deep intragenic mutations in families having two or more consecutive pregnancies with similar aberrant fetal phenotypes.
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http://dx.doi.org/10.1002/ajmg.a.62260DOI Listing
August 2021

Nuclear isoform of FGF13 regulates post-natal neurogenesis in the hippocampus through an epigenomic mechanism.

Cell Rep 2021 May;35(7):109127

Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China; Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 201210, China; Co-innovation Center of Neuroregeneration, School of Medicine, Nantong University, Nantong, Jiangsu 226001, China. Electronic address:

The hippocampus is one of two niches in the mammalian brain with persistent neurogenesis into adulthood. The neurogenic capacity of hippocampal neural stem cells (NSCs) declines with age, but the molecular mechanisms of this process remain unknown. In this study, we find that fibroblast growth factor 13 (FGF13) is essential for the post-natal neurogenesis in mouse hippocampus, and FGF13 deficiency impairs learning and memory. In particular, we find that FGF13A, the nuclear isoform of FGF13, is involved in the maintenance of NSCs and the suppression of neuronal differentiation during post-natal hippocampal development. Furthermore, we find that FGF13A interacts with ARID1B, a unit of Brahma-associated factor chromatin remodeling complex, and suppresses the expression of neuron differentiation-associated genes through chromatin modification. Our results suggest that FGF13A is an important regulator for maintaining the self-renewal and neurogenic capacity of NSCs in post-natal hippocampus, revealing an epigenomic regulatory function of FGFs in neurogenesis.
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http://dx.doi.org/10.1016/j.celrep.2021.109127DOI Listing
May 2021
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