bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary Multi-Physics Performance Analysis and Design Evaluation of UO2 Fuel for LBE-Cooled Subcritical Reactor of China Initiative Accelerator Driven System
Authors: Wang Guan , Gu Long , Yun Di
Published: October 2021

The China initiative Accelerator Driven System (CiADS) and the corresponding lead-bismuth eutectic (LBE) cooled subcritical reactor, as the research subject of one of the major national science and technology infrastructure projects, are undertaken by the Institute of Modern Physics-Chinese Academy of Sciences (IMP-CAS). And in the first phase, UO2 fuels will be loaded in the subcritical core to test the coupling technology and achieve a long-term steady operation. A brief description of CiADS subcritical reactor, fuel assembly and fuel element are presented here, and a multi-physics performance analysis and design evaluation of CiADS UO2 fuel are carried out by means of the FUTURE code. FUTURE is a fuel performance analysis code to evaluate the synergy of phenomena occurring in the fuel element and their impact on the fuel design improvement for the liquid metal fast reactor, which was developed jointly by IMP-CAS and Xi’an Jiaotong University (XJTU). In this paper, the FUTURE code was modified and updated focusing on characteristics of CiADS fuels. Relocation and densification models were added. Results of the hottest fuel element, mainly concerning the thermo-mechanical behaviors, are discussed concerning both fuel and cladding performance on the basis of indicative design limits. According to the preliminary design, the CiADS UO2 fuel exhibits good performance, and the main safety parameters are far below the indicative limits. The Fuel Cladding Mechanical Interaction (FCMI) is not very serious, and the permanent cladding strains and Cumulative Damage Fraction (CDF) are small and even negligible thanks to the low level of fuel temperature and corresponding stress. However, some critical issues may still exist, especially on LBE corrosion near the coolant inlet, where protective oxide layers are very thin from BoL to EoL. The modeling is useful for providing feedback to the conceptual design of the CiADS LBE-cooled subcritical reactor and the update of FUTURE code.
Characteristics of the Waviness End-Face Mechanical Seal in Reactor Coolant Pump Considering the Viscosity-Temperature Effect
Authors: Ma Yu , Wang Ya-Hui , Zhou Hai-Chun , Su Wen-Tao
Published: October 2021

Mechanical seals prevents flow leakages in reactor coolant pumps thus playing an important role in their operational safety. However, their operational performance depends on different parameters, the seal geometrical design and the sealing medium characteristics among others. This study investigates the main performances of the waviness end-face mechanical seal, considering the effect of fluid flow and thermal characteristics. The involved coupled thermal-hydraulic process is simulated using the OpenFOAM, based on the coupled Navier-Stokes and energy balance equations. Study results showed that the viscosity-temperature effect may increase the flow leakage, and decrease both the opening force and the liquid film stiffness. The later may be decreased to negative values under specific conditions. It’s therefore generally found that visco-thermal characteristics of the sealing medium may negatively affect mechanical seal’s operational stability. On the other hand, from the perspective of liquid film temperature rise, the visco-thermal effect may lead to the regulation of the temperature rise in the liquid film, which improves the mechanical seal’s operational safety in some aspects. Through a comprehensive analysis, the optimal structural parameters of the waviness mechanical seal investigated in this study are found to be hi = 2.5μm, β = 900μrad (Rd-Ri)/(Ro-Ri) = 0.2, α = 0.8, and k = 9.
A Multi-Tracer Study of Fresh Water Sources for a Temperate Urbanized Coastal Bay (Southern Baltic Sea)
Authors: von Ahn Cátia Milene Ehlert , Scholten Jan C. , Malik Christoph , Feldens Peter , Liu Bo , Dellwig Olaf , Jenner Anna-Kathrina , Papenmeier Svenja , Schmiedinger Iris , Zeller Mary A. , Böttcher Michael Ernst
Published: October 2021

Terrestrial surface waters and submarine ground water discharge (SGD) act as a source of dissolved substances for coastal systems. Solute fluxes of SGD depend on the ground water composition and the water-solid-microbe interactions close to the sediment-water interface. Thus, this study aims to characterize and evaluate the hydrogeochemical gradients developing in the fresh-salt water mixing zone of the Wismar Bay (WB), southern Baltic Sea, Germany. Sampling campaigns covering the WB, the fresh-salt water mixing zone at the beach of the WB shoreline, terrestrial surface and ground waters near the WB as well sediments pore water were carried out. In these different waters, the distribution of dissolved inorganic carbon, nutrients, major ions, trace elements, stable isotopes (H, O, C, S), and radium isotopes have been investigated. Enhanced concentrations of radium isotopes together with dissolved manganese, barium in the surface waters of the eastern WB indicated benthic-pelagic coupling via the exchange between pore water and the water column. Salinity, stable isotopes, and major ions in sediment pore water profiles identified the presence of fresh ground water below about 40 cmbsf in the central part of the bay. Geophysical acoustic techniques revealed the local impact of anthropogenic sediment excavation, which reduced the thickness of a sediment layer between the coastal aquifer and the bottom water, causing, therefore, a ground water upward flow close to the top sediments. The fresh impacted pore water stable isotope composition (δ18O, δ2H) plot close to the regional meteoric water line indicating a relatively modern ground water source. The calculated organic matter mineralization rates and the dissolved inorganic carbon sediment-water fluxes were much higher at the fresh impacted site when compared to other unimpacted sediments. Therefore, this study reveals that different fresh water sources contribute to the water balance of WB including a SGD source.
Influence of Decadal Ocean Signals on Meteorological Conditions Associated With the Winter Haze Over Eastern China
Authors: Zhang Wen , Dong Xiao , Liu Zhenxin , Lin Renping , Luo Hao
Published: October 2021

The possible influence of the Atlantic multidecadal oscillation (AMO) and the Pacific decadal oscillation (PDO) on the meteorological conditions associated with haze over central eastern China at decadal time scale was investigated using reanalysis and observational dataset for 1979–2018. Four indices, including Siberian high (SH) strength and position indices (SHI/SHPI), a normalized near-surface wind-speed index (WSI) and a potential air temperature gradient index (ATGI), are adopted to denote the meteorological conditions associated with haze. Results shown that the AMO and PDO are both highly correlated with the fluctuation of meteorological factors associated with haze on decadal scale. Although AMO and PDO were in opposite phases during the whole period, since 1997, they both changed phases (AMO shifted to a positive phase and PDO changed to negative) and became favorable for an anomalous dipole-type SLP pattern in the middle-high latitudes of East Asia. The AMO has played a leading role in decadal variation of the large-scale circulation system, while the PDO has had a closer relationship with the lower ventilation condition in eastern China. On the decadal time scale, the AMO stimulates a zonal teleconnection wave train (the AMO northern Hemisphere pattern, ANH) that originates from the North Atlantic Ocean and passes through central Europe, the northern Ural Mountains, Lake Balkhash-Baikal, and central eastern China. During the positive phase of AMO, the ANH induces a stronger and westward shifted SH, with the central eastern China controlled by the anomalous high pressure. In addition, affected by the cyclone (anticyclone) anomaly over Hetao region and North China (the Sea of Japan), southerly wind anomalies dominate over central eastern China. Compared with the AMO, the wave train generated by the negative (positive) PDO phase mainly propagates in the Pacific region, and there is a strong anticyclonic (cyclonic) anomaly over the Northeast Pacific, guiding the air flow southward (northward) along the East Asian coast and thus suppressing (encouraging) the dispersion of pollutants and resulting in above (below)-normal haze episodes.
Comparison of Neighborhood-Scale, Residential Property Flood-Loss Assessment Methodologies
Authors: Mostafiz Rubayet Bin , Friedland Carol J. , Rahman Md Asif , Rohli Robert V. , Tate Eric , Bushra Nazla , Taghinezhad Arash
Published: October 2021

Leading flood loss estimation models include Federal Emergency Management Agency’s (FEMA’s) Hazus, FEMA’s Flood Assessment Structure Tool (FAST), and (U.S.) Hydrologic Engineering Center’s Flood Impact Analysis (HEC-FIA), with each requiring different data input. No research to date has compared the resulting outcomes from such models at a neighborhood scale. This research examines the building and content loss estimates by Hazus Level 2, FAST, and HEC-FIA, over a levee-protected census block in Metairie, in Jefferson Parish, Louisiana. Building attribute data in National Structure Inventory (NSI) 2.0 are compared against “best available data” (BAD) collected at the individual building scale from Google Street View, Jefferson Parish building inventory, and 2019 National Building Cost Manual, to assess the sensitivity of input building inventory selection. Results suggest that use of BAD likely enhances flood loss estimation accuracy over existing reliance on default data in the software or from a national data set that generalizes over a broad scale. Although the three models give similar mean (median) building and content loss, Hazus Level 2 results diverge from those produced by FAST and HEC-FIA at the individual building level. A statistically significant difference in mean (median) building loss exists, but no significant difference is found in mean (median) content loss, between building inventory input (i.e., NSI 2.0 vs BAD), but both the building and content loss vary at the individual building scale due to difference in building-inventory-reported foundation height, foundation type, number of stories, replacement cost, and content cost. Moreover, building loss estimation also differs significantly by depth-damage function (DDF), for flood depths corresponding with the longest return periods, with content loss differing significantly by DDF at all return periods tested, from 10 to 500 years. Knowledge of the extent of estimated differences aids in understanding the degree of uncertainty in flood loss estimation. Much like the real estate industry uses comparable home values to appraise a home, flood loss planners should use multiple models to estimate flood-related losses. Moreover, results from this study can be used as a baseline for assessing losses from other hazards, thereby enhancing protection of human life and property.
Optimization for Cost-Effectively Monitoring Ecological Effects of Water Diversion on the Urban Drinking Water Sources in a Large Eutrophic Lake
Authors: Dai Jiangyu , Feng Zhonghua , Wu Xiufeng , Wu Shiqiang , Zhang Yu , Wang Fangfang , Gao Ang , Lv Xueyan , Zhu Senlin
Published: October 2021

Due to the inputs of allochthonous pollutants and biological species from imported water, ecological effects of water diversion on urban drinking sources require long-term monitoring. Since spatial distributions of biological and environmental elements are always susceptible to water diversion, the monitoring specifications in water-receiving regions are always different from conventional ecological monitoring, especially in monitoring parameter selection and site distribution. To construct the method for selecting sensitive monitoring parameters and optimizing sites distribution in lakes, the large river-to-lake water diversion project, Water Diversion from Yangtze River to Lake Taihu in China, was taken as an example. The physicochemical properties and phytoplankton communities in the water-receiving Gonghu Bay and the referenced lake center were investigated and compared between the water diversion and non-diversion days in different seasons from 2013 to 2014. The comparative and collinearity analyses for selecting sensitive physicochemical parameters to water diversion, and the multidimensional scaling analysis based on the matrices of biological and sensitive physicochemical data, were integrated to optimize the monitoring in the water-receiving lake regions. Seven physicochemical parameters, including water temperature, pH, dissolved oxygen, total nitrogen, total phosphorus, chlorophyll a, and active silicate, were demonstrated to be sensitive to seasonal water diversion activities and selected for optimizing the site distribution and daily water quality monitoring. The nonmetric multidimensional scaling analysis results based on the data matrices of sensitive physicochemical parameters and phytoplankton communities were consistent for sites distribution optimization. For cost-effective monitoring, the sites distribution scheme could choose the optimizing results based on the Euclidean distance from 3.0 to 4.0 and the Bray-Curtis similarity from 40 to 60%. This scheme divided the Gonghu Bay into three water regions: the inflow river inlet, bay center, and bay mouth adjacent to the open water region. In each of the three regions, one representative site could be selected. If focusing on more details of each region, the standards with the Euclidean distance lower than 2.0 and the Bray-Curtis similarity higher than 60% should be considered. This optimization method provided an available way to fulfill the cost-effective long-term monitoring of urban drinking water sources influenced by water diversion projects.
A Putative C2H2 Transcription Factor CgTF6, Controlled by CgTF1, Negatively Regulates Chaetoglobosin A Biosynthesis in Chaetomium globosum
Authors: Yan Yu , Xiang Biyun , Xie Qiaohong , Lin Yamin , Shen Guangya , Hao Xiaoran , Zhu Xudong
Published: October 2021

Gα signaling pathway as well as the global regulator LaeA were demonstrated to positively regulate the biosynthesis of chaetoglobosin A (ChA), a promising biotic pesticide produced by Chaetomium globosum. Recently, the regulatory function of Zn2Cys6 binuclear finger transcription factor CgcheR that lies within the ChA biosynthesis gene cluster has been confirmed. However, CgcheR was not merely a pathway specific regulator. In this study, we showed that the homologs gene of CgcheR (designated as Cgtf1) regulate ChA biosynthesis and sporulation in C. globosum NK102. More importantly, RNA-seq profiling demonstrated that 1,388 genes were significant differentially expressed as Cgtf1 deleted. Among them, a putative C2H2 transcription factor, named Cgtf6, showed the highest gene expression variation in zinc-binding proteins encoding genes as Cgtf1 deleted. qRT-PCR analysis confirmed that expression of Cgtf6 was significantly reduced in CgTF1 null mutants. Whereas, deletion of Cgtf6 resulted in the transcriptional activation and consequent increase in the expression of ChA biosynthesis gene cluster and ChA production in C. globosum. These data suggested that CgTF6 probably acted as an end product feedback effector, and interacted with CgTF1 to maintain a tolerable concentration of ChA for cell survival.
PBX2-Mediated circTLK1 Activates JAK/STAT Signaling to Promote Gliomagenesis via miR-452-5p/SSR1 Axis
Authors: Li Jing , Zhao Zongren , Wang Xiang , Ma Qiong , Ji Huanhuan , Wang Yan , Yu Rutong
Published: October 2021

Glioma is considered one of the most lethal brain tumors, as the aggressive blood vessel formation leads to high morbidity and mortality rates. However, the mechanisms underlying the initiation and progression of glioma remain unclear. Here, we aimed to reveal the role of circTLK1 in glioma development. Our results revealed that circTLK1 is highly expressed in glioma tumor tissues and glioma cell lines. We then conducted a series of experiments that showed that circTLK1 was involved in the progression of gliomas. Mechanistically, investigation of the factors downstream of circTLK1 revealed that circTLK1 activated JAK/STAT signaling in glioma cells. Furthermore, AGO2-RIP, RNA-pull down, and luciferase reporter gene assays led to the identification of the novel circTLK1/miR-452-5p/SSR1 axis. Moreover, we investigated the upstream regulator of circTLK1 and found that circTLK1 expression in glioma cells could be regulated by the transcriptional factor PBX2. Taken together, our findings show that circTLK1 mediated by PBX2 activates JAK/STAT signaling to promote glioma progression through the miR-452-5p/SSR1 pathway. These results provide new insights into glioma diagnosis and therapy.
Small Protein Enrichment Improves Proteomics Detection of sORF Encoded Polypeptides
Authors: Fijalkowski Igor , Peeters Marlies K. R. , Van Damme Petra
Published: October 2021

With the rapid growth in the number of sequenced genomes, genome annotation efforts became almost exclusively reliant on automated pipelines. Despite their unquestionable utility, these methods have been shown to underestimate the true complexity of the studied genomes, with small open reading frames (sORFs; ORFs typically considered shorter than 300 nucleotides) and, in consequence, their protein products (sORF encoded polypeptides or SEPs) being the primary example of a poorly annotated and highly underexplored class of genomic elements. With the advent of advanced translatomics such as ribosome profiling, reannotation efforts have progressed a great deal in providing translation evidence for numerous, previously unannotated sORFs. However, proteomics validation of these riboproteogenomics discoveries remains challenging due to their short length and often highly variable physiochemical properties. In this work we evaluate and compare tailored, yet easily adaptable, protein extraction methodologies for their efficacy in the extraction and concomitantly proteomics detection of SEPs expressed in the prokaryotic model pathogen Salmonella typhimurium (S. typhimurium). Further, an optimized protocol for the enrichment and efficient detection of SEPs making use of the of amphipathic polymer amphipol A8-35 and relying on differential peptide vs. protein solubility was developed and compared with global extraction methods making use of chaotropic agents. Given the versatile biological functions SEPs have been shown to exert, this work provides an accessible protocol for proteomics exploration of this fascinating class of small proteins.
Local Ancestry Adjusted Allelic Association Analysis Robustly Captures Tuberculosis Susceptibility Loci
Authors: Swart Yolandi , Uren Caitlin , van Helden Paul D. , Hoal Eileen G. , Möller Marlo
Published: October 2021

Pulmonary tuberculosis (TB), caused byMycobacterium tuberculosis, is a complex disease. The risk of developing active TB is in part determined by host genetic factors. Most genetic studies investigating TB susceptibility fail to replicate association signals particularly across diverse populations. South African populations arose because of multi-wave genetic admixture from the indigenous KhoeSan, Bantu-speaking Africans, Europeans, Southeast Asian-and East Asian populations. This has led to complex genetic admixture with heterogenous patterns of linkage disequilibrium and associated traits. As a result, precise estimation of both global and local ancestry is required to prevent both false positive and false-negative associations. Here, 820 individuals from South Africa were genotyped on the SNP-dense Illumina Multi-Ethnic Genotyping Array (∼1.7M SNPs) followed by local and global ancestry inference using RFMix. Local ancestry adjusted allelic association (LAAA) models were utilized owing to the extensive genetic heterogeneity present in this population. Hence, an interaction term, comprising the identification of the minor allele that corresponds to the ancestry present at the specific locus under investigation, was included as a covariate. One SNP (rs28647531) located on chromosome 4q22 was significantly associated with TB susceptibility and displayed a SNP minor allelic effect (G allele, frequency = 0.204) whilst correcting for local ancestry for Bantu-speaking African ancestry (p-value = 5.518 × 10−7; OR = 3.065; SE = 0.224). Although no other variants passed the significant threshold, clear differences were observed between the lead variants identified for each ancestry. Furthermore, the LAAA model robustly captured the source of association signals in multi-way admixed individuals from South Africa and allowed the identification of ancestry-specific disease risk alleles associated with TB susceptibility that have previously been missed.
N6-Methyladenosine-Related Long Non-coding RNA Signature Associated With Prognosis and Immunotherapeutic Efficacy of Clear-Cell Renal Cell Carcinoma
Authors: Ma Tianming , Wang Xiaonan , Wang Jiawen , Liu Xiaodong , Lai Shicong , Zhang Wei , Meng Lingfeng , Tian Zijian , Zhang Yaoguang
Published: October 2021

Increasing evidence suggests that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play important roles in cancer progression and immunotherapeutic efficacy in clear-cell renal cell carcinoma (ccRCC). In this study, we conducted a comprehensive ccRCC RNA-seq analysis using The Cancer Genome Atlas data to establish an m6A-related lncRNA prognostic signature (m6A-RLPS) for ccRCC. Forty-four prognostic m6A-related lncRNAs (m6A-RLs) were screened using Pearson correlation analysis (|R| > 0.7, p < 0.001) and univariable Cox regression analysis (p < 0.01). Using consensus clustering, the patients were divided into two clusters with different overall survival (OS) rates and immune status according to the differential expression of the lncRNAs. Gene set enrichment analysis corroborated that the clusters were enriched in immune-related activities. Twelve prognostic m6A-RLs were selected and used to construct the m6A-RLPS through least absolute shrinkage and selection operator Cox regression. We validated the differential expression of the 12 lncRNAs between tumor and non-cancerous samples, and the expression levels of four m6A-RLs were further validated using Gene Expression Omnibus data and Lnc2Cancer 3.0 database. The m6A-RLPS was verified to be an independent and robust predictor of ccRCC prognosis using univariable and multivariable Cox regression analyses. A nomogram based on age, tumor grade, clinical stage, and m6A-RLPS was generated and showed high accuracy and reliability at predicting the OS of patients with ccRCC. The prognostic signature was found to be strongly correlated to tumor-infiltrating immune cells and immune checkpoint expression. In conclusion, we established a novel m6A-RLPS with a favorable prognostic value for patients with ccRCC. The 12 m6A-RLs included in the signature may provide new insights into the tumorigenesis and allow the prediction of the treatment response of ccRCC.
Genome-Wide DNA Methylation Profile in Jejunum Reveals the Potential Genes Associated With Paratuberculosis in Dairy Cattle
Authors: Zhang Junnan , Han Bo , Zheng Weijie , Lin Shan , Li Houcheng , Gao Yahui , Sun Dongxiao
Published: October 2021

Paratuberculosis in cattle causes substantial economic losses to the dairy industry. Exploring functional genes and corresponding regulatory pathways related to resistance or susceptibility to paratuberculosis is essential to the breeding of disease resistance in cattle. Co-analysis of genome-wide DNA methylation and transcriptome profiles is a critically important approach to understand potential regulatory mechanism underlying the development of diseases. In this study, we characterized the profiles of DNA methylation of jejunum from nine Holstein cows in clinical, subclinical, and healthy groups using whole-genome bisulfite sequencing (WGBS). The average methylation level in functional regions was 29.95% in the promoter, 29.65% in the 5’ untranslated region (UTR), 68.24% in exons, 71.55% in introns, and 72.81% in the 3’ UTR. A total of 3,911, 4,336, and 4,094 differentially methylated genes (DMGs) were detected in clinical vs. subclinical, clinical vs. healthy, and subclinical vs. healthy comparative group, respectively. Gene ontology (GO) and analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that these DMGs were significantly enriched in specific biological processes related to immune response, such as Th1 and Th2 cell differentiation, wnt, TNF, MAPK, ECM-receptor interaction, cellular senescence, calcium, and chemokine signaling pathways (q value <0.05). The integration of information about DMGs, differentially expressed genes (DEGs), and biological functions suggested nine genes CALCRL, TNC, GATA4, CD44, TGM3, CXCL9, CXCL10, PPARG, and NFATC1 as promising candidates related to resistance/susceptibility to Mycobacterium avium subspecies paratuberculosis (MAP). This study reports on the high-resolution DNA methylation landscapes of the jejunum methylome across three conditions (clinical, subclinical, and healthy) in dairy cows. Our investigations integrated different sources of information about DMGs, DEGs, and pathways, enabling us to find nine functional genes that might have potential application in resisting paratuberculosis in dairy cattle.
Evaluating Causal Relationship Between Metabolites and Six Cardiovascular Diseases Based on GWAS Summary Statistics
Authors: Qiao Jiahao , Zhang Meng , Wang Ting , Huang Shuiping , Zeng Ping
Published: October 2021

Cardiovascular diseases (CVDs) remain the main cause of morbidity and mortality worldwide. The pathological mechanism and underlying biological processes of these diseases with metabolites remain unclear. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal effect of metabolites on these diseases by making full use of the latest GWAS summary statistics for 486 metabolites and six major CVDs. Extensive sensitivity analyses were implemented to validate our MR results. We also conducted linkage disequilibrium score regression (LDSC) and colocalization analysis to investigate whether MR findings were driven by genetic similarity or hybridization between LD and disease-associated gene loci. We identified a total of 310 suggestive associations across all metabolites and CVDs, and finally obtained four significant associations, including bradykinin, des-arg(9) (odds ratio [OR] = 1.160, 95% confidence intervals [CIs]: 1.080–1.246, false discovery rate [FDR] = 0.022) on ischemic stroke, N-acetylglycine (OR = 0.946, 95%CIs: 0.920–0.973, FDR = 0.023), X-09026 (OR = 0.845, 95%CIs: 0.779–0.916, FDR = 0.021) and X-14473 (OR = 0.938, 95%CIs = 0.907–0.971, FDR = 0.040) on hypertension. Sensitivity analyses showed that these causal associations were robust, the LDSC and colocalization analyses demonstrated that the identified associations were unlikely confused by LD. Moreover, we identified 15 important metabolic pathways might be involved in the pathogenesis of CVDs. Overall, our work identifies several metabolites that have a causal relationship with CVDs, and improves our understanding of the pathogenesis and treatment strategies for these diseases.
Ancient Mitogenomes Provide New Insights into the Origin and Early Introduction of Chinese Domestic Donkeys
Authors: Wang Linying , Sheng Guilian , Preick Michaela , Hu Songmei , Deng Tao , Taron Ulrike H. , Barlow Axel , Hu Jiaming , Xiao Bo , Sun Guojiang , Song Shiwen , Hou Xindong , Lai Xulong , Hofreiter Michael , Yuan Junxia
Published: October 2021

Both molecular data and archaeological evidence strongly support an African origin for the domestic donkey. Recent genetic studies further suggest that there were two distinct maternal lineages involved in its initial domestication. However, the exact introduction time and the dispersal process of domestic donkeys into ancient China are still unresolved. To address these questions, we retrieved three near-complete mitochondrial genomes from donkey specimens excavated from Gaoling County, Shaanxi Province, and Linxia Basin, Gansu Province, China, dated at 2,349-2,301, 469-311, and 2,160-2,004 cal. BP, respectively. Maximum-likelihood and Bayesian phylogenetic analyses reveal that the two older samples fall into the two different main lineages (i.e., clade Ⅰ and clade Ⅱ) of the domestic donkey, suggesting that the two donkey maternal lineages had been introduced into Midwestern China at least at the opening of Silk Road (approximately the first century BC). Bayesian analysis shows that the split of the two donkey maternal lineages is dated at 0.323 Ma (95% CI: 0.583–0.191 Ma) using root-tip dating calibrations based on near-complete mitogenomes, supporting the hypothesis that modern domestic donkeys go back to at least two independent domestication events. Moreover, Bayesian skyline plot analyses indicate an apparent female population increase between 5,000 and 2,500 years ago for clade I followed by a stable population size to the present day. In contrast, clade II keeps a relatively stable population size over the past 5,000 years. Overall, our study provides new insights into the early domestication history of Chinese domestic donkeys.
A Holling Functional Response Model for Mapping QTLs Governing Interspecific Interactions
Authors: Zhang Xiao-Yu , Gong Huiying , Fang Qing , Zhu Xuli , Jiang Libo , Wu Rongling
Published: October 2021

Genes play an important role in community ecology and evolution, but how to identify the genes that affect community dynamics at the whole genome level is very challenging. Here, we develop a Holling type II functional response model for mapping quantitative trait loci (QTLs) that govern interspecific interactions. The model, integrated with generalized Lotka-Volterra differential dynamic equations, shows a better capacity to reveal the dynamic complexity of inter-species interactions than classic competition models. By applying the new model to a published mapping data from a competition experiment of two microbial species, we identify a set of previously uncharacterized QTLs that are specifically responsible for microbial cooperation and competition. The model can not only characterize how these QTLs affect microbial interactions, but also address how change in ecological interactions activates the genetic effects of the QTLs. This model provides a quantitative means of predicting the genetic architecture that shapes the dynamic behavior of ecological communities.
The Predictive Role of Immune Related Subgroup Classification in Immune Checkpoint Blockade Therapy for Lung Adenocarcinoma
Authors: Yu Xiaozhou , Wang Ziyang , Chen Yiwen , Yin Guotao , Liu Jianjing , Chen Wei , Zhu Lei , Xu Wengui , Li Xiaofeng
Published: October 2021

Background: In lung adenocarcinoma (LUAD), the predictive role of immune-related subgroup classification in immune checkpoint blockade (ICB) therapy remains largely incomplete.

Methods: Transcriptomics analysis was performed to evaluate the association between immune landscape and ICB therapy in lung adenocarcinoma and the associated underlying mechanism. First, the least absolute shrinkage and selection operator (LASSO) algorithm and K-means algorithm were used to identify immune related subgroups for LUAD cohort from the Cancer Genome Atlas (TCGA) database (n = 572). Second, the immune associated signatures of the identified subgroups were characterized by evaluating the status of immune checkpoint associated genes and the immune cell infiltration. Then, potential responses to ICB therapy based on the aforementioned immune related subgroup classification were evaluated via tumor immune dysfunction and exclusion (TIDE) algorithm analysis, and survival analysis and further Cox proportional hazards regression analysis were also performed for LUAD. In the end, gene set enrichment analysis (GSEA) was performed to explore the metabolic mechanism potentially responsible for immune related subgroup clustering. Additionally, two LUAD cohorts from the Gene Expression Omnibus (GEO) database were used as validation cohort.

Results: A total of three immune related subgroups with different immune-associated signatures were identified for LUAD. Among them, subgroup 1 with higher infiltration scores for effector immune cells and immune checkpoint associated genes exhibited a potential response to IBC therapy and a better survival, whereas subgroup 3 with lower scores for immune checkpoint associated genes but higher infiltration scores for suppressive immune cells tended to be insensitive to ICB therapy and have an unfavorable prognosis. GSEA revealed that the status of glucometabolic reprogramming in LUAD was potentially responsible for the immune-related subgroup classification.

Conclusion: In summary, immune related subgroup clustering based on distinct immune associated signatures will enable us to screen potentially responsive LUAD patients for ICB therapy before treatment, and the discovery of metabolism associated mechanism is beneficial to comprehensive therapeutic strategies making involving ICB therapy in combination with metabolism intervention for LUAD.
Abnormalities in Gut Microbiota and Metabolism in Patients With Chronic Spontaneous Urticaria
Authors: Wang Xin , Yi Wanyu , He Liting , Luo Shuaihantian , Wang Jiaqi , Jiang Li , Long Hai , Zhao Ming , Lu Qianjin
Published: October 2021

Background

Increasing evidence suggests that the gut microbiome plays a role in the pathogenesis of allergy and autoimmunity. The association between abnormalities in the gut microbiota and chronic spontaneous urticaria (CSU) remains largely undefined.

Methods

Fecal samples were obtained from 39 patients with CSU and 40 healthy controls (HCs). 16S ribosomal RNA (rRNA) gene sequencing (39 patients with CSU and 40 HCs) and untargeted metabolomics (12 patients with CSU and 12 HCs) were performed to analyze the compositional and metabolic alterations of the gut microbiome in CSU patients and HCs.

Results

The 16S rRNA gene sequencing results showed a significant difference in the β-diversity of the gut microbiota, presented as the Jaccard distance, between CSU patients and HCs. No significant differences were found in the α-diversity of the gut microbiota between patients and HCs. At the phylum level, the major bacteria in the gut microbiome of patients with CSU were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. At the genus level, Lactobacillus, Turicibacter, and Lachnobacterium were significantly increased and Phascolarctobacterium was decreased in patients with CSU. PICRUSt and correlation analysis indicated that Lactobacillus, Turicibacter, and Phascolarctobacterium were positively related to G protein-coupled receptors. Metabolomic analysis showed that α-mangostin and glycyrrhizic acid were upregulated and that 3-indolepropionic acid, xanthine, and isobutyric acid were downregulated in patients with CSU. Correlation analysis between the intestinal microbiota and metabolites suggested that there was a positive correlation between Lachnobacterium and α-mangostin.

Conclusions

This study suggests that disturbances in the gut microbiome composition and metabolites and their crosstalk or interaction may participate in the pathogenesis of CSU.
Dexamethasone-Induced FKBP51 Expression in CD4+ T-Lymphocytes Is Uniquely Associated With Worse Asthma Control in Obese Children With Asthma
Authors: Tejwani Vickram , McCormack Amanda , Suresh Karthik , Woo Han , Xu Ningchun , Davis Meghan F. , Brigham Emily , Hansel Nadia N. , McCormack Meredith C. , D’Alessio Franco R.
Published: October 2021

Introduction

There is evidence that obesity, a risk factor for asthma severity and morbidity, has a unique asthma phenotype which is less atopic and less responsive to inhaled corticosteroids (ICS). Peripheral blood mononuclear cells (PBMC) are important to the immunologic pathways of obese asthma and steroid resistance. However, the cellular source associated with steroid resistance has remained elusive. We compared the lymphocyte landscape among obese children with asthma to matched normal weight children with asthma and assessed relationship to asthma control.

Methods

High-dimensional flow cytometry of PBMC at baseline and after dexamethasone stimulation was performed to characterize lymphocyte subpopulations, T-lymphocyte polarization, proliferation (Ki-67+), and expression of the steroid-responsive protein FK506-binding protein 51 (FKBP51). T-lymphocyte populations were compared between obese and normal-weight participants, and an unbiased, unsupervised clustering analysis was performed. Differentially expressed clusters were compared with asthma control, adjusted for ICS and exhaled nitric oxide.

Results

In the obese population, there was an increased cluster of CD4+T-lymphocytes expressing Ki-67 and FKBP51 at baseline and CD4+T-lymphocytes expressing FKBP51 after dexamethasone stimulation. CD4+Ki-67 and FKBP51 expression at baseline showed no association with asthma control. Dexamethasone-induced CD4+FKBP51 expression was associated with worse asthma control in obese participants with asthma. FKBP51 expression in CD8+T cells and CD19+B cells did not differ among groups, nor did polarization profiles for Th1, Th2, Th9, or Th17 percentage.

Discussion

Dexamethasone-induced CD4+FKBP51 expression is uniquely associated with worse asthma control in obese children with asthma and may underlie the corticosteroid resistance observed in this population.
Diphtheria And Tetanus Vaccination History Is Associated With Lower Odds of COVID-19 Hospitalization
Authors: Monereo-Sánchez Jennifer , Luykx Jurjen J. , Pinzón-Espinosa Justo , Richard Geneviève , Motazedi Ehsan , Westlye Lars T. , Andreassen Ole A. , van der Meer Dennis
Published: October 2021

Background

COVID-19 is characterized by strikingly large, mostly unexplained, interindividual variation in symptom severity: while some individuals remain nearly asymptomatic, others suffer from severe respiratory failure. Previous vaccinations for other pathogens, in particular tetanus, may partly explain this variation, possibly by readying the immune system.

Methods

We made use of data on COVID-19 testing from 103,049 participants of the UK Biobank (mean age 71.5 years, 54.2% female), coupled to immunization records of the last ten years. Using logistic regression, covarying for age, sex, respiratory disease diagnosis, and socioeconomic status, we tested whether individuals vaccinated for tetanus, diphtheria or pertussis, differed from individuals that had only received other vaccinations on 1) undergoing a COVID-19 test, 2) being diagnosed with COVID-19, and 3) whether they developed severe COVID-19 symptoms.

Results

We found that individuals with registered diphtheria or tetanus vaccinations are less likely to develop severe COVID-19 than people who had only received other vaccinations (diphtheria odds ratio (OR)=0.47, p-value=5.3*10-5; tetanus OR=0.52, p-value=1.2*10-4).

Discussion

These results indicate that a history of diphtheria or tetanus vaccinations is associated with less severe manifestations of COVID-19. These vaccinations may protect against severe COVID-19 symptoms by stimulating the immune system. We note the correlational nature of these results, yet the possibility that these vaccinations may influence the severity of COVID-19 warrants follow-up investigations.
Identification and Mapping of HBsAg Loss-Related B-Cell Linear Epitopes in Chronic HBV Patients by Peptide Array
Authors: Gu Shuqin , Liu Zhipeng , Lin Li , Zhong Shihong , Ma Yanchen , Li Xiaoyi , Ye Guofu , Wen Chunhua , Li Yongyin , Tang Libo
Published: October 2021

Identification of immunogenic targets against hepatitis B virus (HBV)-encoded proteins will provide crucial advances in developing potential antibody therapies. In this study, 63 treatment-naïve patients with chronic HBV infection and 46 patients who achieved hepatitis B surface antigen loss (sAg loss) following antiviral treatment were recruited. Moreover, six patients who transitioned from the hepatitis B e antigen-positive chronic infection phase (eAg+CInf) to the hepatitis phase (eAg+CHep) were enrolled from real-life clinical practice. Additionally, telbivudine-treated eAg+CHep patients and relapsers or responders from an off-treatment cohort were longitudinally studied. The frequencies and function of B cells were assessed by flow cytometry. We devised a peptide array composed of 15-mer overlapping peptides of HBV-encoded surface (S), core (C), and polymerase (P) proteins and performed a screening on B-cell linear epitopes with sera. Naïve B cells and plasmablasts were increased, whereas total memory, activated memory (AM), and atypical memory (AtM) B cells were reduced in sAg- patients compared with sAg+ patients. Importantly, longitudinal observations found that AtM B cells were associated with successful treatment withdrawal. Interestingly, we identified six S-specific dominant epitopes (S33, S34, S45, S76, S78, and S89) and one C-specific dominant epitope (C37) that reacted with the majority of sera from sAg- patients. Of note, more B-cell linear epitopes were detected in CHep patients with alanine aminotransferase (ALT) flares than in nonflare CInf patients, and five B-cell linear epitopes (S4, S5, S10, S11, and S68) were overwhelmingly recognized by ALT flare patients. The recognition rates of epitopes on C and P proteins were significantly increased in CHep patients relative to CInf patients. Strikingly, a statistically significant elevation in the number of positive epitopes was observed when ALT nonflare patients shifted into the flare phase. Moreover, S76 identified at baseline was confirmed to be associated with a complete response after 48 weeks of telbivudine therapy. Taken together, we identified several functional cure-related B-cell linear epitopes of chronic HBV infection, and these epitopes may serve as vaccine candidates to elicit neutralizing antibodies to treat HBV infection.
Comparative Transcriptomic and Proteomic Analysis of Exopalaemon carinicauda in Response to Alkalinity Stress
Authors: Qin Zhen , Ge Qianqian , Wang Jiajia , Li Mingdong , Liu Ping , Li Jian , Li Jitao
Published: October 2021

Saline-alkaline waters are stressful environments where most aquatic animals can’t survive normally, and alkalinity is one of the key limited environmental factors. Due to strong adaptability to environment, the ridgetail white prawn Exopalaemon carinicauda is a potential good species suitable for large-scale culture in saline-alkaline waters. Exploring its alkaline adaptability mechanism will help to guide more marine crustaceans to saline-alkaline culture. In this study, an integrative analysis of the gill-specific transcriptome and proteome at 0, 12, and 36 h after alkalinity stress was performed to identify important regulators and pathways involved in alkalinity adaption of E. carinicauda. A total of 3,157 differentially expressed genes (DEGs) and 443 differentially expressed proteins (DEPs) were identified at 12 and 36 h compared with 0 h. Base on the transcriptome analysis, the Gene Ontology (GO) enriched terms were mainly related to ion transport, including “calcium-transporting ATPase activity,” “ATPase coupled ion transmembrane transporter activity,” “divalent inorganic cation transmembrane transporter activity,” etc., and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways mainly refer to the processes of endocrine system at both 12, and 36 h. Based on the proteomic analysis, KEGG pathways related to lipolysis and amino acids metabolism were significantly enriched at 12 h, and carbohydrate metabolism and immune response were significantly enriched at 36 h. There were significantly up-regulated expressions of ion transport related genes including aquaporin, carbonic anhydrase, ammonium transporter Rh type A-like, Na+/H+-exchanger, etc., as well as ion transport proteins including V-type proton ATPase 116 kDa subunit a-like isoform X1, sodium-potassium ATPase beta, vesicle associated membrane protein, etc. after alkalinity exposure, which indicating their important roles in response to alkalinity stress. The results of integrated analysis between proteome and transcriptome showed that up-regulated DEG/DEP (aldehyde dehydrogenase) was significantly enriched at 12 h and the up-regulated DEG/DEP (peptidylglycine alpha) was significantly enriched at 36 h, suggesting the two molecules may be critical in response to alkalinity change. This study reveals the first time-course, gill-specific, combined transcriptomic and proteomic profiling associated with alkalinity adaption of E. carinicauda and provides new insights into the mechanisms underlying the molecular response to alkalinity stress in shrimp.
Micro-Scale Permeability Characterization of Carbon Fiber Composites Using Micrograph Volume Elements
Authors: Seuffert Julian , Bittrich Lars , Cardoso de Oliveira Leonardo , Spickenheuer Axel , Kärger Luise
Published: October 2021

To manufacture a high-performance structure made of continuous fiber reinforced plastics, Liquid Composite Molding processes are used, where a liquid resin infiltrates the dry fibers. For a good infiltration quality without dry spots, it is important to predict the resin flow correctly. Knowledge of the local permeability is an essential precondition for mold-filling simulations. In our approach, the intra-bundle permeability parallel and transverse to the fibers is characterized via periodic fluid dynamic simulations of micro-scale volume elements (VE). We evaluate and compare two approaches: First, an approach to generate VEs based on a statistical distribution of the fibers and fiber diameters. Second, an approach based on micrograph images of samples manufactured with Tailored Fiber Placement (TFP) using the measured fiber distribution. The micrograph images show a higher heterogeneity of the distribution than the statistically generated VEs, which is characterized by large resin areas. This heterogeneity leads to a significantly different permeability compared to the stochastic approach. In conclusion, a pure stochastic approach needs to contain the large heterogeneity of the fiber distribution to predict correct permeability values.
Case Report: Management of Primary Tracheobronchial Light Chain Amyloidosis in a Patient With Biclonal Gammopathy Using a Systemic Bortezomib-Based Regimen
Authors: Yan Wei , Li Peng , Wu Cen , Zhou Chuming , Liao Aijun , Yang Wei , Wang Huihan
Published: October 2021

Primary tracheobronchial light chain (AL) amyloidosis is a rare and heterogeneous disease characterized by the buildup of amyloid deposits in the airway mucosa. Although its treatment remains challenging, the current view is that the localized form can be treated conservatively due to its slow progression. While radiotherapy has proven effective in treating localized form of the disease, some patients do not respond to local treatment and continue to experience poor quality of life, highlighting the need to explore additional treatment strategies. In this report, we discuss a case of primary tracheobronchial AL amyloidosis with biclonal gammopathy (IgA κ and IgG κ) in a 46-year-old man who was transferred to our hospital due to dyspnea progression over the preceding 3 years. Chest computed tomography revealed irregular tracheobronchial stenosis with wall thickening, and histological examination of the bronchial biopsies confirmed the diagnosis of endobronchial AL amyloidosis. Owing to the poor effect of radiation therapy and treatments for improving airway patency, he was treated with a systemic chemotherapy regimen [cyclophosphamide-bortezomib-dexamethasone (CyBorD)]. We observed substantial improvements in his dyspnea, highlighting the potential of systemic therapy to improve quality of life of patients with tracheobronchial AL amyloidosis. However, the long-term pathological changes associated with local bronchial lesions require further investigation.