An autonomous activation of interleukin-17 receptor signaling sustains inflammation and promotes disease progression.

Anti-interleukin-17 (IL-17) therapy has been used in various autoimmune diseases. However, the efficacy is unexpectedly limited in several IL-17-associated diseases, and the mechanism of limited efficacy remains unclear. Here, we show that a molecular complex containing the adaptor molecule Act1 and tyrosine phosphatase SHP2 mediated autonomous IL-17R signaling that accelerated and sustained inflammation. SHP2, aberrantly augmented in various autoimmune diseases, was induced by IL-17A itself in astrocytes and keratinocytes, sustaining chemokine production even upon anti-IL-17 therapies. Mechanistically, SHP2 directly interacted with and dephosphorylated Act1, which replaced Act1-TRAF5 complexes and induced IL-17-independent activation of IL-17R signaling. Genetic or pharmacologic inactivation of SHP2, or blocking Act1-SHP2 interaction, paralyzed both IL-17-induced and IL-17-independent signaling and attenuated primary or relapsing experimental autoimmune encephalomyelitis. Therefore, Act1-SHP2 complexes mediate an alternative pathway for autonomous activation of IL-17R signaling, targeting which could be a therapeutic option for IL-17-related diseases in addition to current antibody therapies.

Protein-Protein Interaction Prediction via Structure-Based Deep Learning.

Protein-protein interactions (PPIs) play an essential role in life activities. Many artificial intelligence algorithms based on protein sequence information have been developed to predict PPIs. However, these models have difficulty dealing with various sequence lengths and suffer from low generalization and prediction accuracy. In this study, we proposed a novel end-to-end deep learning framework, RSPPI, combining residual neural network (ResNet) and spatial pyramid pooling (SPP), to predict PPIs based on the protein sequence physicochemistry properties and spatial structural information. In the RSPPI model, ResNet was employed to extract the structural and physicochemical information from the protein three-dimensional structure and primary sequence; the SPP layer was used to transform feature maps to a single vector and avoid the fixed-length requirement. The RSPPI model possessed excellent cross-species performance and outperformed several state-of-the-art methods based either on protein sequence or gene ontology in most evaluation metrics. The RSPPI model provides a novel strategy to develop an AI PPI prediction algorithm.

Carbon Fiber Film with Multi-Hollow Channels to Expedite Oxygen Electrocatalytic Reaction Kinetics for Flexible Zn-Air Battery.

The high oxygen electrocatalytic overpotential of flexible cathodes due to sluggish reaction kinetics result in low energy conversion efficiency of wearable zinc-air batteries (ZABs). Herein, lignin, as a 3D flexible carbon-rich macromolecule, is employed for partial replacement of polyacrylonitrile and constructing flexible freestanding air electrodes (FFAEs) with large amount of mesopores and multi-hollow channels via electrospinning combined with annealing strategy. The presence of lignin with disordered structure decreases the graphitization of carbon fibers, increases the structural defects, and optimizes the pore structure, facilitating the enhancement of electron-transfer kinetics. This unique structure effectively improves the accessibility of graphitic-N/pyridinic-N with oxygen reduction reaction (ORR) activity and pyridinic-N with oxygen evolution reaction (OER) activity for FFAEs, accelerating the mass transfer process of oxygen-active species. The resulting N-doped hollow carbon fiber films (NHCFs) exhibit superior bifunctional ORR/OER performance with a low potential difference of only 0.60 V. The rechargeable ZABs with NHCFs as metal-free cathodes possess a long-term cycling stability. Furthermore, the NHCFs can be used as FFAEs for flexible ZABs which have a high specific capacity and good cycling stability under different bending states. This work paves the way to design and produce highly active metal-free bifunctional FFAEs for electrochemical energy devices.

Establishment and validation of a prediction model for gestational diabetes.

AIM: To develop a visual prediction model for gestational diabetes (GD) in pregnant women and to establish an effective and practical tool for clinical application. METHODS: To establish a prediction model, the modelling set included 1756 women enrolled in the Zunyi birth cohort, the internal validation set included 1234 enrolled women, and pregnant women in the Wuhan cohort were included in the external validation set. We established a demographic-lifestyle factor model (DLFM) and a demographic-lifestyle-environmental pollution factor model (DLEFM) based on whether the women were exposed to environmental pollutants. The least absolute shrinkage and selection lasso-logistic regression analyses were used to identify the independent predictors of GD and construct a nomogram for predicting its occurrence. RESULTS: The DLEFM regression analysis showed that a family history of diabetes (odd ratio [OR] 2.28; 95% confidence interval [CI] 1.05-4.71), a history of GD in pregnant women (OR 4.22; 95% CI 1.89-9.41), being overweight or obese before pregnancy (OR 1.71; 95% CI 1.27-2.29), a history of hypertension (OR 2.61; 95% CI 1.41-4.72), sedentary time (h/day) (OR 1.16; 95% CI 1.08-1.24), monobenzyl phthalate (OR 1.95; 95% CI 1.45-2.67) and Q4 mono-ethyl phthalate concentration (OR 1.85; 95% CI 1.26-2.73) were independent predictors. The area under the receiver operating curves for the internal validation of the DLEFM and the DLFM constructed using these seven factors was 0.827 and 0.783, respectively. The calibration curve of the DLEFM was close to the diagonal line. The DLEFM was thus the more optimal model, and the one which we chose. CONCLUSIONS: A nomogram based on preconception factors was constructed to predict the occurrence of GD in the second and third trimesters. It provided an effective tool for the early prediction and timely management of GD.

Advances towards genome-based acute myeloid leukemia classification: A comparative analysis of WHO-HAEM4R, WHO-HAEM5, and International Consensus Classification.

Two recent guidelines, the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) and the International Consensus Classification (ICC), were published to refine the diagnostic criteria of acute myeloid leukemia (AML). They both consider genomic features more extensively and expand molecularly defined AML subtypes. In this study, we compared the classifications of 1135 AML cases under both criteria. According to WHO-HAEM5 and ICC, the integration of whole transcriptome sequencing, targeted gene mutation screening, and conventional cytogenetic analysis identified defining genetic abnormalities in 89% and 90% of AML patients, respectively. The classifications displayed discrepancies in 16% of AML cases after being classified using the two guidelines, respectively. Both new criteria significantly reduce the number of cases defined by morphology and differentiation. However, their clinical implementation heavily relies on comprehensive and sophisticated genomic analysis, including genome and transcriptome levels, alongside the assessment of pathogenetic somatic and germline variations. Discrepancies between WHO-HAEM5 and ICC, such as the assignment of RUNX1 mutations, the rationality of designating AML with mutated TP53 as a unique entity, and the scope of rare genetic fusions, along with the priority of concurrent AML-defining genetic abnormalities, are still pending questions requiring further research for more elucidated insights.

Iguratimod suppresses plasma cell differentiation and ameliorates experimental Sjögren's syndrome in mice by promoting TEC kinase degradation.

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease with an unclear pathogenesis, and there is currently no approved drug for the treatment of this disease. Iguratimod, as a novel clinical anti-rheumatic drug in China and Japan, has shown remarkable efficacy in improving the symptoms of patients with pSS in clinical studies. In this study we investigated the mechanisms underlying the therapeutic effect of iguratimod in the treatment of pSS. Experimental Sjögren's syndrome (ESS) model was established in female mice by immunizing with salivary gland protein. After immunization, ESS mice were orally treated with iguratimod (10, 30, 100 mg·kg-1·d-1) or hydroxychloroquine (50 mg·kg-1·d-1) for 70 days. We showed that iguratimod administration dose-dependently increased saliva secretion, and ameliorated ESS development by predominantly inhibiting B cells activation and plasma cell differentiation. Iguratimod (30 and 100 mg·kg-1·d-1) was more effective than hydroxychloroquine (50 mg·kg-1·d-1). When the potential target of iguratimod was searched, we found that iguratimod bound to TEC kinase and promoted its degradation through the autophagy-lysosome pathway in BAFF-activated B cells, thereby directly inhibiting TEC-regulated B cells function, suggesting that the action mode of iguratimod on TEC was different from that of conventional kinase inhibitors. In addition, we found a crucial role of TEC overexpression in plasma cells of patients with pSS. Together, we demonstrate that iguratimod effectively ameliorates ESS via its unique suppression of TEC function, which will be helpful for its clinical application. Targeting TEC kinase, a new regulatory factor for B cells, may be a promising therapeutic option.

Exposure levels and determinants of placental polybrominated diphenyl ethers in Chinese pregnant women.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are a group of widely used chemicals and humans are exposed to them in their daily life. PBDEs exposure during pregnancy may have adverse effects on pregnant women and their fetuses. Nevertheless, limited information is available on the levels and determinants of PBDEs exposure in Chinese pregnant women. METHODS: The internal exposure levels of eight PBDEs (BDE-28, 47, 99, 100, 153, 154, 183, and 209) in placental samples of 1280 pregnant women from Zunyi birth cohort were analyzed using gas chromatography tandem mass spectrometry. All PBDEs concentrations were lipid adjusted (ng/g lw). Determinants of exposure were assessed by multivariable logistic regression model. RESULTS: Eight PBDE homologues were quantifiable in more than 70% of the samples. The highest median concentrations were found for BDE-209 (2.78 ng/g lw), followed by BDE-153 (1.00 ng/g lw) and BDE-183 (0.93 ng/g lw). The level of ΣPBDEs ranged from 0.90 to 308.78 ng/g lw, with a median concentration of 10.02 ng/g lw. Multivariate logistic regression analysis showed that maternal age older than 30 years old (OR: 1.59; 95% CI: 1.14, 2.23), pre-pregnancy obesity (1.51; 1.08, 2.10), home renovation within 2 years (1.43; 1.08, 1.91), spending more time outdoors during pregnancy (0.70; 0.55, 0.89), high consumption of fish/seafood (1.46; 1.13, 1.90) and eggs (1.44; 1.04, 2.00), male infant sex (1.69; 1.18, 2.42) were associated with PBDEs exposure. CONCLUSION: The study population is generally exposed to PBDEs, of which BDE-209 is the dominant congener, indicating extensive application of products containing deca-BDE mixtures. Maternal age, pre-pregnancy BMI, home decoration, average outdoor time during pregnancy, fish, seafood, eggs consumption, and fetal sex were exposure-determinning factors. This study contributes to the knowledge on region-specific PBDEs contamination in pregnant women and related risk factors.

A Common Variant of ARRB2 Promoter Region Associated with the Prognosis of Heart Failure.

INTRODUCTION: The role of ARRB2 in cardiovascular disease has recently gained increasing attention. However, the association between ARRB2 polymorphisms and heart failure (HF) has not yet been investigated. METHODS: A total of 2,386 hospitalized patients with chronic HF were enrolled as the first cohort and followed up for a mean period of 20.2 months. Meanwhile, ethnically and geographically matched 3,000 individuals without evidence of HF were included as healthy controls. We genotyped the common variant in ARRB2 gene to identify the association between variant and HF. A replicated independent cohort enrolling 837 patients with chronic HF was applied to validate the observed association. A series of function analyses were conducted to illuminate the underlying mechanism. RESULTS: We identified a common variant rs75428611 associated with the prognosis of HF in two-stage population: adjusted p = 0.001, hazard ratio (HR) = 1.31 (1.11-1.54) in additive model and adjusted p = 0.001, HR = 1.39 (1.14-1.69) in dominant model in first-stage population; adjusted p = 0.04, HR = 1.41 (1.02-1.95) in additive model and adjusted p = 0.03, HR = 1.51 (1.03-2.20) in dominant model in replicated stage. However, rs75428611 did not significantly associate with the risk of HF. Functional analysis indicated that rs75428611-G allele increased the promoter activity and the mRNA expression level of ARRB2 by facilitating transcription factor SRF binding but not the A allele. CONCLUSIONS: Our findings demonstrated that rs75428611 in promoter of ARRB2 was associated with the risk of HF mortality. It is a promising potential treatment target for HF.

Intermediate State between MoSe2 and Janus MoSeS during Atomic Substitution Process.

Janus transition metal dichalcogenides (TMDCs), with dissimilar chalcogen atoms on each side of TMDCs, have garnered considerable research attention because of the out-of-plane intrinsic polarization in monolayer TMDCs. Although a plasma process has been proposed for synthesizing Janus TMDCs based on the atomic substitution of surface atoms at room temperature, the formation dynamics and intermediate electronic states have not been completely examined. In this study, we investigated the intermediate state between MoSe2 and Janus MoSeS during plasma processing. Atomic composition analysis and atomic-scale structural observations revealed the intermediate partially substituted Janus (PSJ) structure. Combined with theoretical calculations, we successfully clarified the characteristic Raman modes in the intermediate PSJ structure. The PL exhibited discontinuous transitions that could not be explained by the theoretical calculations. These findings will contribute toward understanding the formation process and electronic-state modulation of Janus TMDCs.

Regulation of beta-amyloid for the treatment of Alzheimer's disease: Research progress of therapeutic strategies and bioactive compounds.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is difficult to treat. Extracellular amyloid is the principal pathological criterion for the diagnosis of AD. Amyloid ß (Aß) interacts with various receptor molecules on the plasma membrane and mediates a series of signaling pathways that play a vital role in the occurrence and development of AD. Research on receptors that interact with Aß is currently ongoing. Overall, there are no effective medications to treat AD. In this review, we first discuss the importance of Aß in the pathogenesis of AD, then summarize the latest progress of Aß-related targets and compounds. Finally, we put forward the challenges and opportunities in the development of effective AD therapies.

Identification of overlapping and interacting networks reveals intrinsic spatiotemporal organization of the human brain.

The human brain is a complex network that exhibits dynamic fluctuations in activity across space and time. Depending on the analysis method, canonical brain networks identified from resting-state fMRI (rs-fMRI) are typically constrained to be either orthogonal or statistically independent in their spatial and/or temporal domains. We avoid imposing these potentially unnatural constraints through the combination of a temporal synchronization process ("BrainSync") and a three-way tensor decomposition method ("NASCAR") to jointly analyze rs-fMRI data from multiple subjects. The resulting set of interacting networks comprises minimally constrained spatiotemporal distributions, each representing one component of functionally coherent activity across the brain. We show that these networks can be clustered into six distinct functional categories and naturally form a representative functional network atlas for a healthy population. This functional network atlas could help explore group and individual differences in neurocognitive function, as we demonstrate in the context of ADHD and IQ prediction.

Tetrahedral Bonding Structure (Ni3 -Se) Induced by Lattice-Distortion of Ni to Achieve High Catalytic Activity in Na-Se Battery.

Fabrication of transition-metal catalytic materials is regarded as a promising strategy for developing high-performance sodium-selenium (Na-Se) batteries. However, more systematic explorations are further demanded to find out how their bonding interactions and electronic structures can affect the Na storage process. This study finds that lattice-distorted nickel (Ni) structure can form different bonding structures with Na2 Se4 , providing high activity to catalyze the electrochemical reactions in Na-Se batteries. Using this Ni structure to prepare electrode (Se@NiSe2 /Ni/CTs) can realize rapid charge transfer and high cycle stability of the battery. The electrode exhibits high storage performance of Na+ ; i.e., 345 mAh g⁻1 at 1 C after 400 cycles, and 286.4 mAh g⁻1 at 10 C in rate performance test. Further results reveal the existence of a regulated electronic structure with upshifts of the d-band center in the distorted Ni structure. This regulation changes the interaction between Ni and Na2 Se4 to form a Ni3 -Se tetrahedral bonding structure. This bonding structure can provide higher adsorption energy of Ni to Na2 Se4 to facilitate the redox reaction of Na2 Se4 during the electrochemical process. This study can inspire the design of bonding structure with high performance in conversion-reaction-based batteries.

DNTT activation, TdT-aided gene length mutation, and better prognosis in ATG-based regimen allo-HSCT in AML.

This study aimed to investigate the relationship between anomalous DNA nucleotidylexotransferase (DNTT) activation and the mutagenesis of gene length mutations (LMs) in acute myeloid leukemia (AML), and the relevance of their prognosis in antithymocyte globulin (ATG)-based regimen allogeneic hematopoietic stem cell transplantation (allo-HSCT). A cohort of 578 AML cases was enrolled. Next-generation sequencing was performed to screen mutations of 86 leukemia driver genes. RNA-seq was used to analyze gene expression. Prognostic analysis was investigated in 239 AML cases who underwent ATG-based regimen allo-HSCT. We report a refined subtyping algorithm of LMs (type I-IV) based on sequence anatomy considering the TdT-aided mutagenesis mechanism. GC content adjacent to LM junctions, inserted nontemplate nucleotide bases, and DNTT expression analysis supported the DNTT activation and TdT-aided mutagenesis in type II/III LMs in the total AML cohort. Both single-variate and multivariate analyses showed a better overall survival of FLT3 type III compared to type I in a subset of ATG-based regimen allo-HSCT cases. The novel LM subtyping algorithm not only deciphers the etiology of the mutagenesis of LMs but also helps to fine-tune prognosis differentiation in AML. The possible prognostic versatility of this novel LM subtyping algorithm in terms of chemotherapy, targeted therapy, and allo-HSCT merits further investigation.

Vascular and pulmonary effects of ibuprofen on neonatal lung development.

BACKGROUND: Ibuprofen is a nonsteroidal anti-inflammatory drug that is commonly used to stimulate closure of a patent ductus arteriosus (PDA) in very premature infants and may lead to aberrant neonatal lung development and bronchopulmonary dysplasia (BPD). METHODS: We investigated the effect of ibuprofen on angiogenesis in human umbilical cord vein endothelial cells (HUVECs) and the therapeutic potential of daily treatment with 50 mg/kg of ibuprofen injected subcutaneously in neonatal Wistar rat pups with severe hyperoxia-induced experimental BPD. Parameters investigated included growth, survival, lung histopathology and mRNA expression. RESULTS: Ibuprofen inhibited angiogenesis in HUVECs, as shown by reduced tube formation, migration and cell proliferation via inhibition of the cell cycle S-phase and promotion of apoptosis. Treatment of newborn rat pups with ibuprofen reduced pulmonary vessel density in the developing lung, but also attenuated experimental BPD by reducing lung inflammation, alveolar enlargement, alveolar septum thickness and small arteriolar wall thickening. CONCLUSIONS: In conclusion, ibuprofen has dual effects on lung development: adverse effects on angiogenesis and beneficial effects on alveolarization and inflammation. Therefore, extrapolation of the beneficial effects of ibuprofen to premature infants with BPD should be done with extreme caution.

Expression of NEAT1 can be used as a predictor for Dex resistance in multiple myeloma patients.

OBJECTIVE: Multiple myeloma is a heterogeneous disorder and the intratumor genetic heterogeneity contributes to emergency of drug resistance. Dexamethasone has been used clinically for decades for MM. Nevertheless, their use is severely hampered by the risk of developing side effects and the occurrence of Dex resistance. LncRNA NEAT1 plays a oncogenic role and participates in drug resistance in many solid tumors. Therefore, we investigated a potential usefulness of this molecular as a biomarker for diagnosis of MM and possible correlations of NEAT1 expression with drug resistance and prognosis. METHODS: Bone marrow and peripheral blood mononuclear cells samples were collected from 60 newly diagnosed MM patients. The expression of NEAT1expression level were detected by quantitative real-time PCR analyses. The relationship about the expression levels of lncRNA with other clinical and cytogenetic features was analyzed. In addition, we measured to analysis the correlation between the expression of NEAT1 and Dex resistance in MM patients. RESULTS: It was found that the expression of NEAT1 is significantly higher in multiple myeloma patients compared to controls and does not change with other clinical features and cytogenetic features. We further discovered that overexpression of NEAT1 was associated with Dex resistance and a poor prognosis in MM patients. CONCLUSION: LncRNA NEAT1 has a significant value that might act as a promoting factor in the development of MM and may be severed as a diagnostic factor in MM. NEAT1 invovled in Dex resistance, which provide a new interpretation during the chemotherapy for MM.

A closed, autologous bioprocess optimized for TCR-T cell therapies.

Autologous cell therapy has proven to be an effective treatment for hematological malignancies. Cell therapies for solid tumors are on the horizon, however the high cost and complexity of manufacturing these therapies remain a challenge. Routinely used open steps to transfer cells and reagents through unit operations further burden the workflow reducing efficiency and increasing the chance for human error. Here we describe a fully closed, autologous bioprocess generating engineered TCR-T cells. This bioprocess yielded 5-12 × 10e9 TCR-expressing T cells, transduced at low multiplicity of infections, within 7-10 days, and cells exhibited an enriched memory T-cell phenotype and enhanced metabolic fitness. It was demonstrated that activating, transducing, and expanding leukapheresed cells in a bioreactor without any T-cell or peripheral blood mononuclear cell enrichment steps had a high level of T-cell purity (~97%). Several critical process parameters of the bioreactor, including culturing at a high cell density (7e6 cells/mL), adjusting rocking agitations during phases of scale-up, lowering glycolysis through the addition of 2-deoxy- d-glucose, and modulating interleukin-2 levels, were investigated on their roles in regulating transduction efficiency, cell growth, and T-cell fitness such as T-cell memory phenotype and resistance to activation-induced cell death. The bioprocess described herein supports scale-out feasibility by enabling the processing of multiple patients' batches in parallel within a Grade C cleanroom.

Identification of key somatic oncogenic mutation based on a confounder-free causal inference model.

Abnormal cell proliferation and epithelial-mesenchymal transition (EMT) are the essential events that induce cancer initiation and progression. A fundamental goal in cancer research is to develop an efficient method to detect mutational genes capable of driving cancer. Although several computational methods have been proposed to identify these key mutations, many of them focus on the association between genetic mutations and functional changes in relevant biological processes, but not their real causality. Causal effect inference provides a way to estimate the real induce effect of a certain mutation on vital biological processes of cancer initiation and progression, through addressing the confounder bias due to neutral mutations and unobserved latent variables. In this study, integrating genomic and transcriptomic data, we construct a novel causal inference model based on a deep variational autoencoder to identify key oncogenic somatic mutations. Applied to 10 cancer types, our method quantifies the causal effect of genetic mutations on cell proliferation and EMT by reducing both observed and unobserved confounding biases. The experimental results indicate that genes with higher mutation frequency do not necessarily mean they are more potent in inducing cancer and promoting cancer development. Moreover, our study fills a gap in the use of machine learning for causal inference to identify oncogenic mutations.

Covered Stents vs Bare Metal Stents for Aortoiliac Arterial Diseases: A Systematic Review and Meta-Analysis.

PURPOSE: Covered stents and bare metal stents (BMS) have been regarded as viable treatment options for aortoiliac arterial diseases. We performed this systematic review and meta-analysis to compare the efficacy of covered stents with BMS for aortoiliac arterial diseases. MATERIALS AND METHODS: The Cochrane Library, Embase, and Medline databases were searched by 2 authors (C.Z. and Z.W.) to retrieve all studies comparing the outcomes of covered stents vs BMS for aortoiliac arterial diseases. The Cochrane tool and the Newcastle-Ottawa scale were used to assess the risk of bias in randomized controlled trials and observational studies, respectively. The outcomes at the same stage reported in at least 2 studies were pooled together. The fixed effects model combined the data when I2<50%, otherwise the random effects model was applied. The results for dichotomous variables were presented as odds ratio (OR) or risk difference and 95% confidence interval (CI); continuous variables were reported as mean difference and 95% CI. RESULTS: Herein, 10 studies with a total of 1695 limbs were included. The covered stents significantly increased the freedom from target lesion revascularization (OR 2.85, 95% CI: 1.28-6.33, p=0.010) compared to the BMS during a 24-month follow-up. However, no statistically significant difference was found in the technical success, primary patency, secondary patency, major adverse events (MAEs), ankle-brachial index (ABI) improvement, limb salvage, and survival between the two groups. CONCLUSION: Compared to BMS, covered stents appear to have similar technical success, primary patency, secondary patency, MAEs, ABI improvement, limb salvage, and survival but may have advantages in reducing target lesion revascularization. More well-designed, prospective studies are warranted to determine such findings. CLINICAL IMPACT: Covered stents may increase freedom from target lesion revascularization (TLR) compared to bare metal stents (BMS) in the treatment of aortoiliac arterial diseases. However, technical success, primary patency, secondary patency, major adverse events (MAEs), ABI improvement, limb salvage, and survival were similar. The aforementioned results are still not sufficient to draw a solid conclusion about the selection of stents for aortoiliac arterial diseases. More well-designed, prospective studies are warranted to determine such findings.

Managing genomic diversity in conservation programs of Chinese domestic chickens.

BACKGROUND: Effective conservation and utilization of farm animals are fundamental for realizing sustainable increases in food production. In situ and ex situ conservation are the two main strategies that are currently used to protect the genetic integrity of Chinese domestic chicken breeds. However, genomic diversity and population structure have not been compared in these conserved populations. RESULTS: Three hundred and sixty-one individuals from three Chinese domestic chicken breeds were collected from populations conserved in situ and ex situ and genotyped using genotyping-by-sequencing (GBS). First, we used different parameters based on heterozygosity, genomic inbreeding, and linkage disequilibrium to estimate the genomic diversity of these populations, and applied principal component analysis (PCA), neighbor-joining tree, and ADMIXTURE to analyze population structure. We found that the small ex situ conserved populations, which have been maintained in controlled environments, retained less genetic diversity than the in situ conserved populations. In addition, genetic differentiation was detected between the in situ and ex situ conserved populations of the same breed. Next, we analyzed signatures of selection using three statistical methods (fixation index (FST), nucleotide diversity (Pi), and cross-population extended haplotype homozygosity (XP-EHH) to study the genetic footprints that underlie the differentiation between in situ and ex situ conserved populations. We concluded that, in these small populations, differentiation might be caused by genetic drift or by mutations from the original populations. The differentiation observed in the population of Beijing You chicken probably reflects adaptation to environmental changes in temperature and humidity that the animals faced when they were moved from their place of origin to the new site for ex situ conservation. CONCLUSIONS: Conservation programs of three Chinese domestic chicken breeds have maintained their genomic diversity to a sustainable degree. The small ex situ conserved populations, which are maintained in controlled environments, retain less genetic diversity than populations conserved in situ. In addition, the transfer of populations from their place of origin to another site for conservation purposes results in genetic differentiation, which may be caused by genetic drift or adaptation. This study provides a basis for further optimization of in situ and ex situ conservation programs for domestic chicken breeds in China.

Characteristics of exposure to 10 polycyclic aromatic hydrocarbon metabolites among pregnant women: cohort of pregnant women in Zunyi, southwest China.

OBJECTIVE: Our aim was to elucidate the polycyclic aromatic hydrocarbon (PAH) metabolites exposure levels of pregnant women in the underdeveloped region of Zunyi, southwest China. METHODS: Sociodemographic information was collected via questionnaires, and urine samples were collected at the same time. A total of 3047 pregnant women participated in the study. Gas chromatography/mass spectrometry was used to detect the urine concentrations of 10 PAH metabolites. A generalised linear model (GLM) was used to identify predictive factors of PAH metabolites. RESULTS: All PAH metabolites had a detection rate greater than 60% (67.21%-90.57%) except for 4-OH-PHE at 55.54%. The median concentrations were 0.02-0.11 µg/g Cre except for 1-OH-NAP, 2-OH-NAP, 2-OH-FLU and 9-OH-FLU (0.36-0.50 µg/g Cre). The cluster analysis identified the phenanthrene and fluorene metabolite clusters (containing no other metabolites), while naphthalene metabolites (1-OH-NAP, 2-OH-NAP) could not be clustered without other metabolites. GLM analysis identified that pregnant women with the following characteristics have high urinary concentration of PAH metabolites: overweight, in the last trimester of pregnancy, distance between their house and main traffic lines as <5 m, use fuel for cooking, passive smoking, renovated their residence for less than 3 years, middle family income and office workers. CONCLUSION: The results clarified pregnant women from the economically underdeveloped area could be the victims of PAHs. In addition, PAHs present a demographic and seasonal differential distribution, which will aid in the development of targeted interventions and reduce exposure to PAHs during pregnancy.