bluuebunny/crossref_metadata_2025 huggingface dataset:
Occurrence of uranium, thorium and rare earth elements in the environment: A review
Authors: Patel Khageshwar Singh , Sharma Saroj , Maity Jyoti Prakash , Martín-Ramos Pablo , Fiket Željka , Bhattacharya Prosun , Zhu Yanbei
Published: January 2023

Uranium, thorium, and rare earth elements (REEs) are important strategic elements in today’s world with a range of applications in high and green technology and power generation. The expected increase in demand for U, Th, and REEs in the coming decades also raises a number of questions about their supply risks and potential environmental impacts. This review provides an overview of the current literature on the distribution of these elements in different environmental compartments. For example, the processes of extraction, use, and disposal of U-, Th-, and REE-containing materials have been reported to result in elevated concentrations of these elements in air, in some places even exceeding permissible limits. In natural waters, the above processes resulted in concentrations as high as 69.2, 2.5, and 24.8 mg L−1for U, Th, and REE, respectively, while in soils and sediments they sometimes reach 542, 75, and 56.5 g kg−1, respectively. While plants generally only take up small amounts of U, Th, and REE, some are known to be hyperaccumulators, containing up to 3.5 and 13.0 g kg−1of U and REE, respectively. It appears that further research is needed to fully comprehend the fate and toxicological effects of U, Th, and REEs. Moreover, more emphasis should be placed on developing alternative methods and technologies for recovery of these elements from industrial and mining wastes.
High-frequency monitoring through in-situ fluorometric sensors: A supporting tool to long-term ecological research on lakes
Authors: Rogora Michela , Cancellario Tommaso , Caroni Rossana , Kamburska Lyudmila , Manca Dario , Musazzi Simona , Tiberti Rocco , Lami Andrea
Published: January 2023

Lake Maggiore is a site of the Long-Term Ecosystem Research (LTER) network, belonging to the deep subalpine Lake District in Northern Italy. Studies on the physical, chemical, and biological features of the lake have been performed continuously since the 1980s. The lake recovered from eutrophication reaching the present oligotrophic condition. In the last decade, climate change represents the main driving factor for the long-term evolution of the lake, affecting its hydrodynamics, nutrient status, and biological communities. In 2020 a high-frequency monitoring (HFM) system was deployed, with the aim to integrate long-term monitoring based on discrete sampling and analysis. The system consists of a buoy equipped with sensors for limnological variables and algal pigments. The high-frequency monitoring program is part of a cross-border project between Italy and Switzerland focusing on lake quality monitoring as a critical input for successful lake management. In this paper we focus on Chlorophyll-a data, with the aim to test whether in-situ fluorescence measurements may provide a reliable estimate of lake phytoplankton biovolume and its seasonal dynamic. Sensor’s performance was regularly tested comparing chlorophyll-a data taken by the in-situ fluorescent sensors (Cyclops7, Turner Design), data from laboratory fluorescence analysis (FluoroProbe, BBE Moldaenke), values obtained from chlorophyll-a analysis by UV-VIS spectrophotometry and data from phytoplankton microscopy analysis. We found a general good agreement between the Chlorophyll-a data obtained with the different methods, confirming the use of in-situ sensors as a reliable approach to measure algal pigments, especially to assess their variability in the short-term, but also to describe the seasonal pattern of phytoplankton biovolume. However, phytoplankton community composition played a substantial role in the performance of the different methods and in the reliability of in-situ data as a tool to assess algal biovolume. This study demonstrates that high-frequency monitoring (HFM), used in conjunction with discrete chemical and biological monitoring, represents an important advance and support in the long-term monitoring of freshwaters and is a useful tool to detect ecological changes. Regular checking and validation of the sensor readings through laboratory analyses are important to get trustworthy data.
The impact of intelligent manufacturing on industrial green total factor productivity and its multiple mechanisms
Authors: Yang Zhihong , Shen Yang
Published: January 2023

As an integration of artificial intelligence and advanced manufacturing technology, intelligent manufacturing has realized the innovation of manufacturing mode and created conditions for the green development of industry. After constructing a theoretical framework between intelligent manufacturing and industrial green total factor productivity, this paper uses panel data of 30 provinces in China from 2006 to 2020, and expresses the level of intelligent manufacturing with industrial robot density, to discuss the economic effects and mechanisms of intelligent manufacturing. The results show that intelligent manufacturing has a positive effect on industrial green total factor productivity, and the panel quantile regression model indicates that there is an increasing marginal effect. With the quantile points going from low to high, the coefficient and statistical significance become larger. Human capital is the mechanism for intelligent manufacturing to improve industrial green total factor productivity. Green technology innovation and producer service industry agglomeration have strengthened the positive effect. There is also heterogeneity in the effect, and the stronger the effect in regions launched local pilot schemes for carbon emissions trading and industrial green transformation development policy. In order to give full play to the technological dividend and empower sustainable industrial development, the paper argues that we need to accelerate the integration of artificial intelligence and manufacturing technology, thus improving the level of industrial intelligence and empowering green development.
Gardens of life: Multifunctional and ecosystem services of urban cemeteries in Central Europe and beyond—Historical, structural, planning, nature and heritage conservation aspects
Authors: Säumel Ina , Butenschön Sylvia , Kreibig Nina
Published: January 2023

Cemeteries are often seen as monofunctional spaces for burial and mourning and, within the dynamically changing urban fabric, as a planning conundrum. Long periods of stability have also turned these untouched and hidden places into refugia for nature and wildlife. In booming and dense cities with high land use pressures and housing shortages, in particular, as the amount of burial ground needed per citizen decreases and burial cultures change, the cemetery has become a contested nature, as a simultaneous space of emotion, commerce and community. We revisited the diversity and ontogenesis of cemeteries, and the interactions with neighboring uses of the urban matrix. Our review demonstrates a wide range of different ecosystem services of urban cemeteries, beyond potential as hotspots of culture and biodiversity. We highlight their multifunctional character and the need for a holistic and trans-disciplinary evaluation using multistakeholder approaches to further develop cemeteries as a crucial element of sustainable urban landscapes.
Environmental, social, governance risk versus cooperation models between financial institutions and businesses. Sectoral approach and ESG risk analysis
Authors: Zioło Magdalena , Bąk Iwona , Cheba Katarzyna , Filipiak Beata Zofia , Spoz Anna
Published: January 2023

Introduction:ESG risk and the business sector are essential in the process of adapting business models towards sustainability. The article aims to analyze ESG risk, taking into account these business sectors that are most affected by ESG risk, and to identify the relationship between ESG risk and cooperation models of financial institutions and companies (Anglo-Saxon/German-Japanese). The original research approach was based on including the financial system model in the analysis of ESG risk impact and the companies’ methods of achieving sustainable business models with external funding.

Methods:The study is based on a two-stage analysis. First, fuzzy cognitive maps are used to evaluate the strength and direction of the relations between factors included in the companies’ sustainable business models according to the business sectors. At the second stage, a correspondence analysis was carried out to distinguish four groups of companies’ industries characterized by homogenous features related to the business sector, sustainable business model (SBM), and the way to transform to sustainability.

Results:Methods of achieving sustainability in companies’ business models differ depending on business sectors. The “financial institution—company” cooperation model and recommendations were proposed.

Discussion:Financial institutions play a crucial role in financing the transition into sustainable business models. However, their impact differs depending on the business sector and the model of the financial system (bank or market oriented). The study assumes that the financial system model determines the form of cooperation between financial institutions and companies in the process of financing costs towards sustainability.
River engage: Insights on plastic debris polluting the Aturukuku River in Uganda, the Ayung River in Indonesia, and the Connecticut River in the United States
Authors: Owens Katharine A. , Kamil Puspita Insan , Ochieng Hannington
Published: January 2023

Introduction: Plastic waste in freshwater ecosystems is increasingly recognized as an economic, ecological, and environmental problem with potential health consequences. This article shares the results of a project to train local stakeholders to collect debris in their communities using scientific methods, then share the results with policymakers.

Methods: Workshops were held in Uganda, Indonesia, and the United States in the spring of 2022. This article presents baseline data from collections on the Aturukuku River in Uganda, the Ayung River in Indonesia, and the Connecticut River in the United States as well as survey results measuring participant attitudes, behaviors, and their perceptions around plastic waste and policy. Surveying participants sheds light on the nuances of perception of the problem and policies to combat pollution at each locale.

Results: We found deposited debris at each riverbank location: Aturukuku River, 0.45 pieces/m2 of which 89.4% was plastic; Ayung River, 7.62 pieces/m2 of which 91.1% was plastic, and the Connecticut River 0.29 pieces/m2 of which 63% was plastic. Environmental attitudes and behaviors were comparable among countries. Participants in all three countries expect plastic will be the most frequently found material.

Discussion: In all cases, perceptions about the kind of debris in their communities corresponds well with collection results. Perceptions around policy solutions included a wide range of solutions, though countries differed in whether solutions addressed the source or the symptoms of the problem; solutions focused more on waste management in Uganda and Indonesia.
The prominence of fossil energy resources in ecological sustainability of BRICS: The key role of institutional worth
Authors: Zhang Jie , Ullah Sami , Khan Karamat
Published: January 2023

Introduction: The relationship between fossil fuel energy resources and environmental degradation has been quantified from theoretical and empirical perspectives. However, none of these studies has considered the conditioning role played by institutions in the nexus, especially for BRICS countries. Therefore, the current study examines the moderating role of institutional quality using annual data from 1996–2018 for BRICS countries.

Method: The study employs the novel cross-sectional augmented autoregressive distributed lags (CS-ARDL) estimator, robust to cross-sectional dependency and heterogeneity, for short-run and long-run estimation. Moreover, augmented mean group (AMG) and common correlated effects mean group (CCEMG) estimators are used for robustness analysis.

Results: The finding reveals that fossil fuel energy resources, globalization, and growth significantly positively affect the ecological footprint, whereas the institutional quality significantly negatively effects the ecological footprint in BRICS countries. Furthermore, the interaction term of institutional quality with fossil fuel energy resources significantly negatively moderates the fossil fuel energy-EFP nexus. Finally, we performed the Dumitrescu and Hurlin (DH) panel causality analysis to determine the causality direction between the variables. Except for intuitions quality and growth, we found a unidirectional causality for explanatory variables and EFP.

Discussion: The study provides novel empirical evidence and recommends the importance of institutional quality for environmental sustainability.
Exploring the characteristics and driving forces of orchard expansion in ecological fragile region: A case study of three typical counties in the Loess Plateau
Authors: Hu Qiyuan , Gao Xiang , Wang Sijia , Wang Qihan , Qin Yuting , Zhang Weiyi , Lun Fei , Li Zhuo
Published: January 2023

The Loess Plateau exemplifies the type of ecologically fragile region that faces severe poverty challenges in China. Orchards have expanded rapidly over the past few decades and now constitute a considerable part of local economy. Not only do the characteristics of orchard expansion affect local economic development, but also exert additional pressure on the ecological environment. Therefore, it is essential for sustainable development on the Loess Plateau to investigate the characteristics and driving forces of orchard expansion. The Fuxian, Luochuan, Huangling, three typical orchard planting counties were chosen as the study area. Firstly, the orchard was extracted from the land use/cover classification from 1990–2020. It broadens the research approach to the identification of expansion cash crops by using the combination of linear spectral mixture analysis (LSMA) and decision tree. Secondly, the spatiotemporal dynamics of orchard expansion were quantitatively investigated based on spatial geometry center shift, physical geographical features, landscape pattern and orchard planting suitability. Then, we constructed an evaluation indicators system to detect the feature importance and partial dependence of different factors by random forest regression. It is more innovative to employ the machine learning method to investigate driving forces. Finally, the linkages between planting suitability and orchard expansion were further discussed, and subsequent policies were proposed. Findings demonstrated the orchard had continuously expanded over the past 30 years, with the fastest expansion rate during 1990–2005. Increased cohesion was accompanied by a shift in the orchard’s spatial distribution to the north central region and highly suitable planting regions. Slope turned out to be the primary factor affecting the orchard expansion. In the future, regions with aging orchard but high planting suitability should be the preferred choice for orchard expansion. Additionally, the transportation connectivity and governmental assistance are crucial considerations for the future planning of the orchard.
Analysis of the coupling characteristics of land transfer and carbon emissions and its influencing factors: A case study of China
Authors: Zhang Maomao , Zhang Ziyi , Tong Bin , Ren Bing , Zhang Lei , Lin Xuehan
Published: January 2023

The rapid and disorderly expansion of urban construction land has exacerbated the contradiction between land use and low-carbon development. In this paper, we use the spatial autocorrelation model and coupling model to analyze the spatial characteristics of the coupled coordination degree of land transfer and carbon emissions in 291 cities in China. The multi-scale geographically weighted regression (MGWR) model is used to explore the spatial heterogeneity of the influence of socioeconomic factors on their coupled coordination degree. The results show that: from 2005 to 2015, the scale of land transfer and carbon emissions has been increasing quantitatively and spatially showing a shift from the southeast coast to the central and western regions. In 2005, 2010, and 2015, the global Moran’s I of the coupled coordination degree are 0.3045, 0.3725, and 0.3388, respectively, indicating that the coupled coordination degree between land transfer and carbon emissions has a significant positive spatial autocorrelation. The MGWR model indicates that the influence of socioeconomic factors on the coupling coordination degree has significant spatial heterogeneity at different time nodes. In 2005 and 2015, the coefficients of the NGR on the coupling coordination of land transfer and carbon emissions have obvious stratification characteristics, with the coefficients decreasing from northeast to southwest. In 2010, the high coefficient (0.924∼0.989) of GPC is mainly distributed in the central region. The coefficient of the PD ranges from 0.464 to 0.918, but the difference of influence degree between the southeast coast and the northwest is obvious. This study may provide new clues for sustainable urban development and carbon reduction.
Correlation analysis of urban building form and PM2.5 pollution based on satellite and ground observations
Authors: Yu Rui
Published: January 2023

Fine particulate matter (PM2.5) pollution is a key issue affecting the health of urban residents. To explore the impact of urban building form on PM2.5 pollution, this study focused on Wuhan, a Chinese megacity. Based on the urban building data, various building form indices were first calculated in grids to quantitatively present the spatial distribution of urban buildings. The city-scale PM2.5 distribution was obtained with satellite remote sensing and ground air pollution monitoring data. The impact of urban building forms on PM2.5 pollution distribution was then analyzed. The results show that the changes in PM2.5 concentration in Wuhan in the north–south direction have a relatively obvious correlation with the windward area ratio of buildings. The dense north–south buildings can slow the spread of near-surface particulate pollution. This finding demonstrates that the building blocking effect of PM2.5 diffusion in Wuhan is significant. The results of this study can provide a reference for urban planning, architectural design, and air pollution control strategies.
Optimizing the evaluation model of green building management based on the concept of urban ecology and environment
Authors: Lyu Chengxi , Hu Jiaxi , Zhang Rui , Chen Wang , Xu Pengpeng
Published: January 2023

Eco-city and green building are the global development strategies today. In order to improve the management level of green buildings in the urbanization process, a reciprocal symbiosis evaluation index model is proposed based on the theory of urban ecology. On this basis, the collaborative relationship model between Eco-city and green building is established, and the green building management framework based on the collaborative theory is constructed. The expert survey method was used to determine the evaluation indicators and analyze the relationship between various city subsystems. Then, the analytic hierarchy process is used to build a three-level evaluation index system, including the target layer, the criterion layer, and the index layer. The weight of the evaluation index system is calculated by combining of the chromatography method and the entropy weight method, and a scientific evaluation index system is established. The gray comprehensive evaluation method is used to evaluate the construction of the green building management system. Based on the index system, the analytic hierarchy process is used to calculate different weight coefficients, which makes the evaluation model easy to use and lays a foundation for subsequent research.
Decomposing niche components reveals simultaneous effects of opposite deterministic processes structuring alpine small mammal assembly
Authors: Song Wen-Yu , Onditi Kenneth Otieno , Li Xue-You , Chen Zhong-Zheng , He Shui-Wang , Li Quan , Jiang Xue-Long
Published: January 2023

Introduction

Species distribution in alpine areas is constrained by multiple abiotic and biotic stressors. This leads to discrepant assembly patterns between different locations and study objects as opposite niche-based processes—limiting similarity and habitat filtering—simultaneously structure communities, masking overall patterns. We aimed to address how these processes structure small mammal communities in the alpine tree line transition zone, one of the most distinct vegetation transitions between alpine and montane habitats.

Methods

We compiled a dataset of species checklist, phylogeny, and functional traits from field collection and published sources spanning 18 mountains in southwest China. We first examined hypothetical niche-based processes with frequently used phylogenetic and trait approaches using this dataset. The species traits were decomposed into different niche components to explore the respective effects of specific stressors. Indices representing evolutionary history, trait space, and pairwise species distance were estimated and compared with null model expectations. Linear mixed-effect models were used to assess the association patterns between diversity indices and elevation.

Results

The results indicated that phylogenetic and functional richness were positively correlated with species richness. In contrast, distance-based indices were either negatively or weakly positively correlated with species richness. Null model analyses suggested no evidence of non-random phylogenetic or overall trait patterns. However, the resource acquisition niche tended to be more overdispersed (positive slopes), while the habitat affinity niche tended to be more clustered (negative slopes) beyond the high elevation tree line.

Discussion

These findings show that opposite niche-based processes simultaneously structure small mammal communities in alpine areas. Overall, the present study provides vital insights into the complexity of assembly processes in these habitats. It also highlights the importance of relating relevant traits to distinguish the influences of specific abiotic and biotic stressors.
The association between plasma chemokines and breast cancer risk and prognosis: A mendelian randomization study
Authors: Yu Xingxing , Zhang Yanyu , Lin Yuxiang , Zou Shuqing , Zhu Pingxiu , Song Mengjie , Fu Fangmeng , Yang Haomin
Published: January 2023

Background: Despite the potential role of several chemokines in the migration of cytotoxic immune cells to prohibit breast cancer cell proliferation, a comprehensive view of chemokines and the risk and prognosis of breast cancer is scarce, and little is known about their causal associations.

Methods: With a two-sample Mendelian randomization (MR) approach, genetic instruments associated with 30 plasma chemokines were created. Their genetic associations with breast cancer and its survival by molecular subtypes were extracted from the recent genome-wide association study of 133,384 breast cancer cases and 113,789 controls, with available survival information for 96,661 patients. We further tested the associations between the polygenic risk score (PRS) for chemokines and breast cancer in the UK Biobank cohort using logistic regression models, while the association with breast cancer survival was tested using Cox regression models. In addition, the association between chemokine expression in tumors and breast cancer survival was also analyzed in the TCGA cohort using Cox regression models.

Results: Plasma CCL5 was causally associated with breast cancer in the MR analysis, which was significant in the luminal and HER-2 enriched subtypes and further confirmed using PRS analysis (OR = 0.94, 95% CI = 0.89–1.00). A potential causal association with breast cancer survival was only found for plasma CCL19, especially for ER-positive patients. Although not replicated in the UK Biobank, we still found an inverse association between CCL19 expression in tumors and breast cancer overall and relapse-free survival in the TCGA cohort (HR = 0.58, 95% CI = 0.35–0.95).

Conclusion: We observed an inverse association between genetic predisposition to CCL5 and breast cancer, while CCL19 was associated with breast cancer survival. These associations suggested the potential of these chemokines as tools for breast cancer prevention and treatment.
Evolutionary genomics: Insights from the invasive European starlings
Authors: Stuart Katarina C. , Sherwin William B. , Edwards Richard J. , Rollins Lee A
Published: January 2023

Two fundamental questions for evolutionary studies are the speed at which evolution occurs, and the way that this evolution may present itself within an organism’s genome. Evolutionary studies on invasive populations are poised to tackle some of these pressing questions, including understanding the mechanisms behind rapid adaptation, and how it facilitates population persistence within a novel environment. Investigation of these questions are assisted through recent developments in experimental, sequencing, and analytical protocols; in particular, the growing accessibility of next generation sequencing has enabled a broader range of taxa to be characterised. In this perspective, we discuss recent genetic findings within the invasive European starlings in Australia, and outline some critical next steps within this research system. Further, we use discoveries within this study system to guide discussion of pressing future research directions more generally within the fields of population and evolutionary genetics, including the use of historic specimens, phenotypic data, non-SNP genetic variants (e.g., structural variants), and pan-genomes. In particular, we emphasise the need for exploratory genomics studies across a range of invasive taxa so we can begin understanding broad mechanisms that underpin rapid adaptation in these systems. Understanding how genetic diversity arises and is maintained in a population, and how this contributes to adaptability, requires a deep understanding of how evolution functions at the molecular level, and is of fundamental importance for the future studies and preservation of biodiversity across the globe.
Mapping the FtsQBL divisome components in bacterial NTD pathogens as potential drug targets
Authors: Kaur Harbinder , Lynn Andrew M.
Published: January 2023

Cytokinesis is an essential process in bacterial cell division, and it involves more than 25 essential/non-essential cell division proteins that form a protein complex known as a divisome. Central to the divisome are the proteins FtsB and FtsL binding to FtsQ to form a complex FtsQBL, which helps link the early proteins with late proteins. The FtsQBL complex is highly conserved as a component across bacteria. Pathogens like Vibrio cholerae, Mycobacterium ulcerans, Mycobacterium leprae, and Chlamydia trachomatis are the causative agents of the bacterial Neglected Tropical Diseases Cholera, Buruli ulcer, Leprosy, and Trachoma, respectively, some of which seemingly lack known homologs for some of the FtsQBL complex proteins. In the absence of experimental characterization, either due to insufficient resources or the massive increase in novel sequences generated from genomics, functional annotation is traditionally inferred by sequence similarity to a known homolog. With the advent of accurate protein structure prediction methods, features both at the fold level and at the protein interaction level can be used to identify orthologs that cannot be unambiguously identified using sequence similarity methods. Using the FtsQBL complex proteins as a case study, we report potential remote homologs using Profile Hidden Markov models and structures predicted using AlphaFold. Predicted ortholog structures show conformational similarity with corresponding E. coli proteins irrespective of their level of sequence similarity. Alphafold multimer was used to characterize remote homologs as FtsB or FtsL, when they were not sufficiently distinguishable at both the sequence or structure level, as their interactions with FtsQ and FtsW play a crucial role in their function. The structures were then analyzed to identify functionally critical regions of the proteins consistent with their homologs and delineate regions potentially useful for inhibitor discovery.
Pan-cancer analysis of the prognostic and immunological role of Fanconi anemia complementation group E
Authors: Zhou Zhixian , Yin Huan , Suye Suye , He Jiarong , Fu Chun
Published: January 2023

Fanconi anemia (FA) genes contribute to tumorigenesis by regulating DNA repair. Despite its importance for assembly and functionality of the FA core complex, no pan-cancer analysis of FANCE was performed. We aimed to provide a comprehensive understanding of the role of FANCE in cancers. Based on The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype Tissue-Expression (GTEx), Human Protein Atlas (HPA), Gene Expression Omnibus (GEO), and Cancer Single-cell Atlas (CancerSEA) databases, we investigated the carcinogenicity of FANCE using various bioinformatics methods, including FANCE expression and prognosis, immune invasion, tumor mutation burden, microsatellite instability, and neoantigens. We monitored Fance mutations in mice that caused tumorigenesis. FANCE expression and activity scores were upregulated in 15 and 21 cancers. High expression of FANCE affected shorter overall survival (OS) in seven cancers and longer overall survival in three cancers. It was correlated with shorter overall survival and progression-free interval (PFI) in endometrial cancer and longer overall survival and PFI in cervical cancer. FANCE expression negatively correlated with stromal/immune scores in 21 cancers including cervical cancer, endometrial cancer, and ovarian cancer. FANCE expression negatively correlated with CD8 T cells in endometrial cancer and positively correlated with M1 macrophages in cervical cancer, possibly related to cancer prognosis. FANCE positively correlated with immune checkpoint inhibitors PD-1, PD-L1, and CTLA4 in endometrial cancer and ovarian cancer. FANCE expression positively correlated with microsatellite instability, tumor mutational burden, and neoantigens in 7, 22, and five cancers, especially in endometrial cancer, potentially increasing the effectiveness of immunotherapy. Single-cell sequencing data showed FANCE was primarily expressed in cancer cells in cervical and ovarian cancer, and in fibroblasts in endometrial cancer. Fance heterozygous mutant mice had increased tumor incidences and shorter overall survival and tumor-free survival (TFS) than Fance homozygous mutant mice and wild-type mice. Conclusively, FANCE potential to serve as a biomarker for cancer prognosis and may predict cancer immunotherapy responses. Fance heterozygous mutant resulted in increased tumorigenesis and poor prognosis in mice.
Clinical, genetic, and experimental research of hyperphenylalaninemia
Authors: Chen Anqi , Pan Yukun , Chen Jinzhong
Published: January 2023

Hyperphenylalaninemia (HPA) is the most common amino acid metabolism defect in humans. It is an autosomal-recessive disorder of the phenylalanine (Phe) metabolism, in which high Phe concentrations and low tyrosine (Tyr) concentrations in the blood cause phenylketonuria (PKU), brain dysfunction, light pigmentation and musty odor. Newborn screening data of HPA have revealed that the prevalence varies worldwide, with an average of 1:10,000. Most cases of HPA result from phenylalanine hydroxylase (PAH) deficiency, while a small number of HPA are caused by defects in the tetrahydrobiopterin (BH4) metabolism and DnaJ heat shock protein family (Hsp40) member C12 (DNAJC12) deficiency. Currently, the molecular pathophysiology of the neuropathology associated with HPA remains incompletely understood. Dietary restriction of Phe has been highly successful, although outcomes are still suboptimal and patients find it difficult to adhere to the treatment. Pharmacological treatments, such as BH4 and phenylalanine ammonia lyase, are available. Gene therapy for HPA is still in development.
Development and validation of a prognostic prediction model for iron metabolism-related genes in patients with pancreatic adenocarcinoma
Authors: Wei Wenhan , Cao Bin , Xu Dongchao , Liu Yusheng , Zhang Xiaofeng , Wang Yu
Published: January 2023

Background: Pancreatic adenocarcinoma (PAAD) is one of the most aggressive tumors of the digestive tract, with low surgical resection rate and insensitivity to radiotherapy and chemotherapy. Existing evidence suggests that regulation of ferroptosis can induce PAAD cell death, inhibit tumor growth, and may synergistically improve the sensitivity of other antitumor drugs. However, there is little of systematic research on iron metabolism-related genes in PAAD. In this study, a risk-score system of PAAD iron metabolism-related genes was designed and tested, and verified to be robust.

Materials and Methods: The TCGA database was used to download 177 PAAD patients’ message RNA (mRNA) expression profiles and clinical characteristics. By identifying dysregulated iron metabolism-related genes between PAAD related tissues and adjacent normal tissues, univariate Cox proportional hazards regression and LASSO regression algorithm were used to establish prognostic risk-score system and construct nomogram to estimate the 1-, 2-, 3-year survival in PAAD patients. Finally, selected genes were validated by quantitative PCR (q-PCR).

Results: A 9-gene related to iron metabolism risk-score system of PAAD was constructed and validated. The clinicopathological characteristics of age, histologic grade, pathologic stage, T stage, residual tumor, and primary therapy outcome were all worse in patients with a higher risk-score. Further, immunohistochemistry results of SLC2A1, MBOAT2, XDH, CTSE, MOCOS, and ATP6V0A4 confirmed that patients with higher expression are more malignant. Then, a nomogram with 9-gene risk score system as a separate clinical factor was utilized to foretell the 1-, 2-, 3-year overall survival rate of PAAD patients. Results of q-PCR showed that 8 of the 9 genes screened were significantly up-regulated in at least one PAAD cell line, and one gene was significantly down-regulated in three PAAD cell lines.

Conclusion: To conclude, we generated a nine-gene system linked to iron metabolism as an independent indicator for predicting PAAD prognosis, therefore presenting a possible prognostic biomarker and potential treatment targets for PAAD.
Skin-specific transgenic overexpression of ovine β-catenin in mice
Authors: Wang Jiankui , Cui Kai , Hua Guoying , Han Deping , Yang Zu , Li Tun , Yang Xue , Zhang Yuanyuan , Cai Ganxian , Deng Xiaotian , Deng Xuemei
Published: January 2023

β-catenin is a conserved molecule that plays an important role in hair follicle development. In this study, we generated skin-specific overexpression of ovine β-catenin in transgenic mice by pronuclear microinjection. Results of polymerase chain reaction (PCR) testing and Southern blot showed that the ovine β-catenin gene was successfully transferred into mice, and the exogenous β-catenin gene was passed down from the first to sixth generations. Furthermore, real-time fluorescent quantitative PCR (qRT-PCR) and western blot analysis showed that β-catenin mRNA was specifically expressed in the skin of transgenic mice. The analysis of F6 phenotypes showed that overexpression of β-catenin could increase hair follicle density by prematurely promoting the catagen-to-anagen transition. The results showed that ovine β-catenin could also promote hair follicle development in mice. We, therefore, demonstrate domestication traits in animals.
Gastroesophageal reflux disease and oral symptoms: A two-sample Mendelian randomization study
Authors: Jiang Shijing , Zheng Liang , Miao Zhiwei
Published: January 2023

Background: The association between Gastroesophageal reflux disease (GERD) and oral symptoms has been reported in observational studies, but the causality of GERD to oral symptoms remained unknown. We aimed to assess the causal effect of GERD on five oral symptoms (mouth ulcers, toothache, loose teeth, bleeding gums, and periodontitis) using the two-sample Mendelian randomization (MR) method.

Methods: Summary-level statistics for GERD and five oral symptoms were obtained from large-scale genome-wide association studies. Rigorous quality control of genetic instruments was conducted before MR analysis. Several analytical methods, including the inverse-variance weighted (IVW) method, MR-Egger regression, weighted median, maximum likelihood, and robust adjusted profile score (RAPS) were utilized, and the results of IVW were taken as the main results. The MR-Egger intercept test, Cochran’s Q test, and leave-one-out test were used as sensitivity analysis for quality control.

Results: After Bonferroni, IVW detected a significant effect of GERD on mouth ulcers (OR = 1.008, 95% CI = 1.003–1.013, p = 0.003), loose teeth (OR = 1.009, 95% CI = 1.005–1.012, p = 9.20 × 10−7), and periodontitis (OR = 1.229, 95% CI = 1.081–1.398, p = 0.002). Consistent patterns of associations were observed across several MR models and sensitivity analysis found little evidence of bias. Nominal significant associations were observed in toothache and bleeding gums (p < 0.05), and heterogeneity was detected.

Conclusion: Our MR analyses supported the positive causal effect of GERD on oral symptoms, especially for mouth ulcers, loose teeth, and periodontitis. Our findings might shed light on the mechanism of oral disease and might imply that oral care should be enhanced in patients with GERD.
Inference of gene-environment interaction from heterogeneous case-parent trios
Authors: Ratnasekera Pulindu , Graham Jinko , McNeney Brad
Published: January 2023

Introduction: In genetic epidemiology, log-linear models of population risk may be used to study the effect of genotypes and exposures on the relative risk of a disease. Such models may also include gene-environment interaction terms that allow the genotypes to modify the effect of the exposure, or equivalently, the exposure to modify the effect of genotypes on the relative risk. When a measured test locus is in linkage disequilibrium with an unmeasured causal locus, exposure-related genetic structure in the population can lead to spurious gene-environment interaction; that is, to apparent gene-environment interaction at the test locus in the absence of true gene-environment interaction at the causal locus. Exposure-related genetic structure occurs when the distributions of exposures and of haplotypes at the test and causal locus both differ across population strata. A case-parent trio design can protect inference of genetic main effects from confounding bias due to genetic structure in the population. Unfortunately, when the genetic structure is exposure-related, the protection against confounding bias for the genetic main effect does not extend to the gene-environment interaction term.

Methods: We show that current methods to reduce the bias in estimated gene-environment interactions from case-parent trio data can only account for simple population structure involving two strata. To fill this gap, we propose to directly accommodate multiple population strata by adjusting for genetic principal components (PCs).

Results and Discussion: Through simulations, we show that our PC adjustment maintains the nominal type-1 error rate and has nearly identical power to detect gene-environment interaction as an oracle approach based directly on population strata. We also apply the PC-adjustment approach to data from a study of genetic modifiers of cleft palate comprised primarily of case-parent trios of European and East Asian ancestry. Consistent with earlier analyses, our results suggest that the gene-environment interaction signal in these data is due to the self-reported European trios.
A novel transcription factor-based signature to predict prognosis and therapeutic response of hepatocellular carcinoma
Authors: Yang Yanbing , Ye Xuenian , Zhang Haibin , Lin Zhaowang , Fang Min , Wang Jian , Yu Yuyan , Hua Xuwen , Huang Hongxuan , Xu Weifeng , Liu Ling , Lin Zhan
Published: January 2023

Background: Hepatocellular carcinoma (HCC) is one of the most common aggressive malignancies with increasing incidence worldwide. The oncogenic roles of transcription factors (TFs) were increasingly recognized in various cancers. This study aimed to develop a predicting signature based on TFs for the prognosis and treatment of HCC.

Methods: Differentially expressed TFs were screened from data in the TCGA-LIHC and ICGC-LIRI-JP cohorts. Univariate and multivariate Cox regression analyses were applied to establish a TF-based prognostic signature. The receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of the signature. Subsequently, correlations of the risk model with clinical features and treatment response in HCC were also analyzed. The TF target genes underwent Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, followed by protein-protein-interaction (PPI) analysis.

Results: A total of 25 differentially expressed TFs were screened, 16 of which were related to the prognosis of HCC in the TCGA-LIHC cohort. A 2-TF risk signature, comprising high mobility group AT-hook protein 1 (HMGA1) and MAF BZIP transcription factor G (MAFG), was constructed and validated to negatively related to the overall survival (OS) of HCC. The ROC curve showed good predictive efficiencies of the risk score regarding 1-year, 2-year and 3-year OS (mostly AUC >0.60). Additionally, the risk score independently predicted OS for HCC patients both in the training cohort of TCGA-LIHC dataset (HR = 2.498, p = 0.007) and in the testing cohort of ICGC-LIRI-JP dataset (HR = 5.411, p < 0.001). The risk score was also positively correlated to progressive characteristics regarding tumor grade, TNM stage and tumor invasion. Patients with a high-risk score were more resistant to transarterial chemoembolization (TACE) treatment and agents of lapatinib and erlotinib, but sensitive to chemotherapeutics. Further enrichment and PPI analyses demonstrated that the 2-TF signature distinguished tumors into 2 clusters with proliferative and metabolic features, with the hub genes belonging to the former cluster.

Conclusion: Our study identified a 2-TF prognostic signature that indicated tumor heterogeneity with different clinical features and treatment preference, which help optimal therapeutic strategy and improved survival for HCC patients.
Exploring prognostic indicators in the pathological images of ovarian cancer based on a deep survival network
Authors: Wu Meixuan , Zhu Chengguang , Yang Jiani , Cheng Shanshan , Yang Xiaokang , Gu Sijia , Xu Shilin , Wu Yongsong , Shen Wei , Huang Shan , Wang Yu
Published: January 2023

Background: Tumor pathology can assess patient prognosis based on a morphological deviation of tumor tissue from normal. Digitizing whole slide images (WSIs) of tissue enables the use of deep learning (DL) techniques in pathology, which may shed light on prognostic indicators of cancers, and avoid biases introduced by human experience.

Purpose: We aim to explore new prognostic indicators of ovarian cancer (OC) patients using the DL framework on WSIs, and provide a valuable approach for OC risk stratification.

Methods: We obtained the TCGA-OV dataset from the NIH Genomic Data Commons Data Portal database. The preprocessing of the dataset was comprised of three stages: 1) The WSIs and corresponding clinical data were paired and filtered based on a unique patient ID; 2) a weakly-supervised CLAM WSI-analysis tool was exploited to segment regions of interest; 3) the pre-trained model ResNet50 on ImageNet was employed to extract feature tensors. We proposed an attention-based network to predict a hazard score for each case. Furthermore, all cases were divided into a high-risk score group and a low-risk one according to the median as the threshold value. The multi-omics data of OC patients were used to assess the potential applications of the risk score. Finally, a nomogram based on risk scores and age features was established.

Results: A total of 90 WSIs were processed, extracted, and fed into the attention-based network. The mean value of the resulting C-index was 0.5789 (0.5096–0.6053), and the resulting p-value was 0.00845. Moreover, the risk score showed a better prediction ability in the HRD + subgroup.

Conclusion: Our deep learning framework is a promising method for searching WSIs, and providing a valuable clinical means for prognosis.
Genetic heritability as a tool to evaluate the precision of 24-hour recall dietary questionnaire variables in UK Biobank
Authors: Cole Joanne B. , Westerman Kenneth E. , Manning Alisa K. , Florez Jose C. , Hirschhorn Joel N.
Published: January 2023

A variety of statistical approaches in nutritional epidemiology have been developed to enhance the precision of dietary variables derived from longitudinal questionnaires. Correlation with biomarkers is often used to assess the relative validity of these different approaches, however, validated biomarkers do not always exist and are costly and laborious to collect. We present a novel high-throughput approach which utilizes the modest but importantly non-zero influence of genetic variation on variation in dietary intake to compare different statistical transformations of dietary variables. Specifically, we compare the heritability of crude averages with Empirical Bayes weighted averages for 302 correlated dietary variables from multiple 24-hour recall questionnaires in 177 K individuals in UK Biobank. Overall, the crude averages for frequency of consumption are more heritable than their Empirical Bayes counterparts only when the reliability of that item across questionnaires is high (measured by intra-class correlation), otherwise, the Empirical Bayes approach (for both unreliably measured frequencies and for average quantities independent of reliability) leads to higher heritability estimates. We also find that the more heritable versions of each dietary variable lead to stronger underlying statistical associations with specific genetic loci, many of which have well-known mechanisms, further supporting heritability as an alternative metric for relative validity in nutritional epidemiology and beyond.
Proteome changes of dairy calves rumen epithelium from birth to postweaning
Authors: Zheng Kaizhi , Wu Jianliang , Ullah Saif , Cao Yang , Jiang Yongqing , Huang Xin , Jiang Junfang
Published: January 2023

Background: Rumen epithelium plays a central role in absorbing, transporting, and metabolizing of short-chain fatty acids. For dairy calves, the growth of rumen papillae greatly enhances the rumen surface area to absorb nutrients. However, the molecular mechanism underlying dairy calves rumen postnatal development remains rarely understood.

Results: Here, we firstly describe the histological change of rumen epithelium from birth to day 90 of age. Then, a shotgun approach and bioinformatics analyses were used to investigate and compare proteomic profiles of Holstein calve rumen epithelium on day 0, 30, 60 and 90 of age. A total of 4372 proteins were identified, in which we found 852, 342, 164 and 95 differentially expressed proteins between D0 and D30, between D30 and D60, between D60 and D90, respectively. Finally, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to provide a comprehensive proteomic landscape of dairy calves rumen development at tissue level.

Conclusion: To conclude, our data indicated that keratinocyte differentiation, mitochondrion formation, the establishment of urea transport and innate immune system play central roles during rumen epithelium development. Tetrahydrobiopterin (BH4) presents an important role in rumen epithelial keratinization. The biological processes of BH4 biosynthesis and molecular function of nicotinamide adenine dinucleotide phosphate binding participate in mitochondrial cristae formation. The proposed datasets provide a useful basis for future studies to better comprehend dairy calves rumen epithelial development.