bluuebunny/crossref_metadata_2025 huggingface dataset:
Methodology for updating GO-FLOW model to handle scenario changes in nuclear power plants
Authors: Xinyu Dai , Ming Yang , Jipu Wang , Zhihui Xu , Hanguan Wen
Published: January 2023

The design of a nuclear power plant is proved to be safe enough in various hypothetical operation scenarios after strict safety assessment. One of the important tasks of operational risk management in a nuclear power plant is to evaluate whether any configuration change of the nuclear power plant can still achieve its expected safety and economic goals. This paper proposes a system reliability modeling and analysis method based on two-layers hierarchical GO-FLOW model. By flexibly adjusting the parameters of a GO-FLOW model, the model can adapt to the changes of success criteria and various configuration of the modeled system, thus avoiding the extra workload brought by re-modeling and improving the efficiency of risk management in nuclear power plants.
Current status and technology development in implementing low carbon emission energy on underground coal gasification (UCG)
Authors: Takyi Shadrack Adjei , Zhang Yindi , Si Mengting , Zeng Fanjin , Li Yingnan , Tontiwachwuthikul Paitoon
Published: January 2023

Although coal mining has played a substantial role in world’s development as a critical fuel source for at least 25 years, its value is partly offset by the massive environmental issues it presents during combustion. The shift to a net-zero CO2 emission will open unique possibilities for new coal technological models in which progressive studies and policies, development, and modernization will play a significant role. Therefore, a collection of technologies has been proposed, one of which is cost-effective is the Underground Coal Gasification (UCG) coupled with carbon capture storage (CCS) and utilization technology (CCU) UCG-CCS/CCU. This paper reviews the current status and technology development in implementing low carbon emission energy on underground coal gasification. The study, therefore, leads to discussing the modern stage of underground coal gasification and carbon capture storage development, recent pilot operations, and current developments of the growing market. At the same time, it provides a reference for underground coal gasification combined with CCUS technology.
The effect of meteoric water on the very fine crystalline dolomite reservoir in the shallow burial zone: A case study of the Ma55 submember of Majiagou Formation in Ordos Basin
Authors: Lan Haoxiang , Guo Min , Fu Meiyan , Deng Hucheng , Gluyas Jon , Xu Wang , Tang Mingyuan , Wu Dong , Li Yilin , Guo Hengwei
Published: January 2023

The meteoric water has obviously changed the physical properties of dolostone reservoirs in the vertical vadose zone and the horizontal phreatic zone, but its influence on the dolostone reservoirs in the shallow burial zone beneath the phreatic surface is still unclear. This study aims to reveal the effect of meteoric water on the dolostone reservoirs in the shallow burial zone through X-ray diffraction, cathodoluminescence, C, O, and Sr isotope using the sample from Majiagou Formation in the Daniudi gas field, Ordos Basin. The diagenesis and paragenesis of the Ma 55 submember were identified and interpreted through petrological study, combined with data from electron probe, X-ray diffraction analysis, and geochemical parameters of diagenetic minerals. The color of the very fine crystalline dolomite under the cathodeluminescence is dark red and red. The order degree of dolomite ranges from 0.54 to 0.91, showing the origin of early seepage-reflux dolomitization. There are a large number of different calcite cements as fills within the pores and fractures. The color of the calcite cement under the cathodoluminescence is orange-yellow, with a zonal structure. Hydrothermal fluid during late diagenesis could be identified by the authigenic fluorite filling in the fractures. According to the assembly of diagenetic minerals, the very fine crystalline dolostones have experienced the seepage-reflux dolomitization, meteoric water dissolution, shallow burial cementation and late cementation. The void spaces of the very fine crystalline dolostones are intercrystalline pores and microfractures. Although a large number of dissolved pores and caves developed in the period of meteoric water dissolution, these caves and dissolved pores has been mostly filled by multi-stages of cementation. Therefore, the effect of meteoric water on dolostone reservoirs in the shallow burial zone beneath the phreatic surface is not obvious. The main controlling factor for the quality of dolostone reservoir was dolomitization. This study provides a new understanding of the influence of meteoric water on reservoir quality in the shallow burial zone during the paleokarst period.
Fault diagnosis of a mixed-flow pump under cavitation condition based on deep learning techniques
Authors: Tan Yangyang , Wu Guoying , Qiu Yanlin , Fan Honggang , Wan Jun
Published: January 2023

Deep learning technique is an effective mean of processing complex data that has emerged in recent years, which has been applied to fault diagnosis of a wide range of equipment. In the present study, three types of deep learning techniques, namely, stacked autoencoder (SAE) network, long short term memory (LSTM) network, and convolutional neural network (CNN) are applied to fault diagnosis of a mixed-flow pump under cavitation conditions. Vibration signals of the mixed-flowed pump are collected from experiment measurements, and then employed as input datasets for deep learning networks. The operation status is clarified into normal, minor cavitation, and severe cavitation conditions according to visualized bubble density. The techniques of FFT and dropout algorithms are also applied to improve diagnosis accuracy. The results show that the diagnosis accuracy based on SAE and LSTM networks is lower than 50%, while is higher than 68% when using CNN. The maximum accuracy can reach 87.2% by mean of a combination of CNN, BN, MLP, and using frequency domain data by FFT as inputs, which validates the feasibility of applying CNN in mixed-flow pumps.
Erosion-reducing potential of Salix psammophila roots in the water–wind crisscrossed erosion region of the Chinese Loess Plateau: A simulated investigation
Authors: Zhang Zheng , Yu Weijie , Li Qiang , Sun Hui , Feng Zhidao , Zou Jiatong
Published: January 2023

Laboratory-simulated experiments under a one-way wind erosion–rain erosion sequence were conducted to investigate the effect of S. psammophila roots on wind and water erosion processes and quantify its erosion-reducing potential. With the collected soil of sandy loam and planted shrub of S. psammophila, 16 soil boxes including bare and root-permeated soils were arranged in March 2017 and conducted in August 2017. With the wind speeds of 11 and 14 m s−1 and rainfall intensities of 60 and 100 mm h−1, two levels of interaction (11 m s−1 × 60 mm h−1 and 14 m s−1 × 100 mm h−1) were designed. The particle-size composition and sediment transport flux were examined in the former wind tunnel experiments, and the runoff hydrodynamic parameters and runoff and water erosion rates were determined in the following rainfall tests. The sediment reduction effect by roots (%) was used to quantify the erosion-reducing potential of roots. The results demonstrated that in the former wind tunnel experiments, compared with the bare soils, the root-permeated soils showed a slight coarsening of surface soil and had 18.03% and 35.71% less sediment transport flux at wind speeds of 11 and 14 m s−1, respectively. In the following rainfall tests, S. psammophila roots weakened the hydrodynamic intensity of overland flow and decreased runoff and water erosion rates by 13.34%, 30.70% and 4.44%, 43.72% at rainfall intensities of 60 and 100 mm h−1, respectively. Different from the water erosion process of bare soils, which showed an increased fluctuated trend, the root-permeated soils presented a steady increase in the early stage of rainfall and then a decrease-stable trend at the mid and end of rainfall. In the wind tunnel–rainfall experiments, the sediment reduction effect by Salix psammophila roots showed 24.37% and 39.72% at levels of 11 m s−1 × 60 mm h−1 and 14 m s−1 × 100 mm h−1, respectively. This kind of study may provide more insights into understanding ecological impacts of sandy vegetation construction on the water–wind crisscrossed erosion region of the Chinese Loess Plateau and also sandy land.
Effects of soil grain size and solution chemistry on the transport of biochar nanoparticles
Authors: Zhang Wenke , Meng Jun , Huang Yuwei , Sarkar Binoy , Singh Bhupinder Pal , Zhou Xuanwei , Gao Jian , Teng Yunpeng , Wang Hailong , Chen Wenfu
Published: January 2023

Biochar nanoparticles (BC-NP) have attracted significant attention because of their unique environmental behavior, some of which could potentially limit large-scale field application of biochar. Accurate prediction of the fate and transportability of BC-NP in soil matrix is the key to evaluating their environmental influence. This study investigated the effects of soil grain size and environmentally relevant solution chemistry, such as ionic strength (cation concentration, 0.1 mM–50 mM; cation type, Na+, and Ca2+), and humic acid (HA; 0–10 mg/L), on the transport behavior of BC-NP via systematic column experiments. The transportability of BC-NP in the soil-packed column decreased with decreasing soil grain size and was inversely proportional to soil clay content. At low cation concentrations (0.1–1.0 mM), a considerable proportion of BC-NP (15.95%–67.17%) penetrated the soil columns. Compared with Na+, Ca2+ inhibited the transportability of BC-NP in the soil through a charge shielding effect. With increasing HA concentration, the transportability of BC-NP increased, likely due to an enhanced repulsion force between BC-NP and soil particles. However, at a high HA concentration (10 mg/L), Ca2+ bridging reduced the transportability of BC-NP in the soil. Breakthrough curves of BC-NP were explained by the two-site kinetic retention model. The antagonistic effects of ionic strength and HA indicated that the transport behavior of BC-NP in the soil was governed by competitive effects of some environmental factors, including soil grain size, environmental solution chemistry, and natural organic matter content.
The PNAE (National School Feeding Program) activity system and its mediations
Authors: Alves Da Silva Eliane , Pedrozo Eugenio Avila , Nunes Da Silva Tania
Published: January 2023

The National School Feeding Program (PNAE—Programa Nacional de Alimentação Escolar) is a Brazilian policy that attends to 44 billion students per year, distributed in 5,568 municipalities, providing school meals to public school students. Law No. 11,947 establishes a minimum percentage of 30% to purchase foodstuffs directly from family farming. In addition to the general rules, it is possible to create specific rules for the operationalization of the program; therefore, this paper aims to characterize the dynamic process of the relationships and actions of social agents involved through the Activity System generated by Law No. 11,947 of 2009 in the municipality of Porto Velho in the state of Rondônia, located in the western Amazon. As a theoretical framework, cultural-historical activity theory (CHAT) and mediated action theory (MAT) were used. To achieve the objective, qualitative research and abductive reasoning were adopted, using a unique and incorporated case study as a strategy. In all, 49 interviews were conducted and analyzed using content analysis. The extent of the influenced community and the different realities to which the actors are exposed were verified.
Local working collections as the foundation for an integrated conservation of Theobroma cacao L. in Latin America
Authors: Lavoie Andréanne , Thomas Evert , Olivier Alain
Published: January 2023

The intraspecific diversity of cacao has traditionally been preserved in genebanks. However, these establishments face various challenges, notably insufficient funding, accession redundancy, misidentification and lack of wild cacao population samples. In natural environments, it is expected that unknown varieties of cacao may still be found, but wild populations of cacao are increasingly threatened by climate change, deforestation, habitat loss, land use changes and poor knowledge. Farmers also retain diversity, but on-farm conservation is affected by geopolitical, economic, management and cultural issues, that are influenced at multiple scales, from the household to the international market. Taking separately, ex situ, in situ and on-farm conservation have not achieved adequate conservation fostering the inclusion of all stakeholders and the broad use of cacao diversity. We analyze the use of the traditional conservation strategies (ex situ, in situ and on-farm) and propose an integrated approach based on local working collections to secure cacao diversity in the long term. We argue that national conservation networks should be implemented in countries of origin to simultaneously maximize alpha (diversity held in any given working collection), beta (the change in diversity between working collections in different regions) and gamma diversity (overall diversity in a country).
Comparative transcriptome analyses of immune responses to LPS in peripheral blood mononuclear cells from the giant panda, human, mouse, and monkey
Authors: Li Shun , Li Caiwu , Chen Lixiang , Yang Hua , Ren Xiaonan , Xu Chunhua , Wu Bin , Wang Chao , Ling Yun , Shen Yinzhong , Lu Hongzhou , Liu Weiping , Zhou Xiaohui
Published: January 2023

Gram-negative bacteria are major pathogens that can cause illnesses in giant pandas. Lipopolysaccharides (LPS), components of Gram-negative bacteria, can activate immune responses in mammals (i.e., humans and mice) through recognition by toll-like receptors (TLRs). However, the giant pandas’ immune response to LPS stimulation and the differences between the giant panda and other mammals are not fully known. In this study, we administrated peripheral blood mononuclear cells (PBMCs) from giant pandas, humans, C57BL/6 mice, and rhesus monkeys by LPS treatment at 6 h followed by RNA sequencing (RNA-seq), respectively, with control of non-stimulation. KEGG analyses of differentially expressed genes (DEGs) pathways indicated that LPS could activate the classic signaling pathway of NF-κB in PBMCs from those four tested species. Thus, similar to the other three species, NF-κB is an LPS-responsive regulator of innate immune responses in giant pandas. Furthermore, the expression patterns of adapter genes, inflammatory cytokine genes, chemokines, interferon genes, cytokine genes related to cell growth and development, costimulatory molecules, Th1/Th2 cytokine genes, Th17 cytokine genes, Th9, and Th22 cytokine genes were compared among giant pandas and three other species. Our data indicated that in addition to the similar expression patterns of certain genes among giant pandas and other species, the unique expression pattern response to LPS in giant pandas was also discovered. Furthermore, Th9, Th17, and Th22 cells might be involved in the response to LPS in giant pandas at this tested time point. This study reveals that LPS-induced immune responses have different sensitivities and response timelines in giant pandas compared with other mammals. This study facilitates further understanding of the role of the TLR signaling pathway and the immune system in giant pandas, which might be helpful for disease prevention and protection.
Identification and experimental validation of key m6A modification regulators as potential biomarkers of osteoporosis
Authors: Qiao Yanchun , Li Jie , Liu Dandan , Zhang Chenying , Liu Yang , Zheng Shuguo
Published: January 2023

Osteoporosis (OP) is a severe systemic bone metabolic disease that occurs worldwide. During the coronavirus pandemic, prioritization of urgent services and delay of elective care attenuated routine screening and monitoring of OP patients. There is an urgent need for novel and effective screening diagnostic biomarkers that require minimal technical and time investments. Several studies have indicated that N6-methyladenosine (m6A) regulators play essential roles in metabolic diseases, including OP. The aim of this study was to identify key m6A regulators as biomarkers of OP through gene expression data analysis and experimental verification. GSE56815 dataset was served as the training dataset for 40 women with high bone mineral density (BMD) and 40 women with low BMD. The expression levels of 14 major m6A regulators were analyzed to screen for differentially expressed m6A regulators in the two groups. The impact of m6A modification on bone metabolism microenvironment characteristics was explored, including osteoblast-related and osteoclast-related gene sets. Most m6A regulators and bone metabolism-related gene sets were dysregulated in the low-BMD samples, and their relationship was also tightly linked. In addition, consensus cluster analysis was performed, and two distinct m6A modification patterns were identified in the low-BMD samples. Subsequently, by univariate and multivariate logistic regression analyses, we identified four key m6A regulators, namely, METTL16, CBLL1, FTO, and YTHDF2. We built a diagnostic model based on the four m6A regulators. CBLL1 and YTHDF2 were protective factors, whereas METTL16 and FTO were risk factors, and the ROC curve and test dataset validated that this model had moderate accuracy in distinguishing high- and low-BMD samples. Furthermore, a regulatory network was constructed of the four hub m6A regulators and 26 m6A target bone metabolism-related genes, which enhanced our understanding of the regulatory mechanisms of m6A modification in OP. Finally, the expression of the four key m6A regulators was validated in vivo and in vitro, which is consistent with the bioinformatic analysis results. Our findings identified four key m6A regulators that are essential for bone metabolism and have specific diagnostic value in OP. These modules could be used as biomarkers of OP in the future.
Identification of ubiquitination-related gene classification and a novel ubiquitination-related gene signature for patients with triple-negative breast cancer
Authors: Zhao Kankan , Zheng Yuan , Lu Wenliang , Chen Bo
Published: January 2023

Background: Ubiquitination-related genes (URGs) are important biomarkers and therapeutic targets in cancer. However, URG prognostic prediction models have not been established in triple-negative breast cancer (TNBC) before. Our study aimed to explore the roles of URGs in TNBC.

Methods: The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and the Gene Expression Omnibus (GEO) databases were used to identify URG expression patterns in TNBC. Non-negative matrix factorization (NMF) analysis was used to cluster TNBC patients. The least absolute shrinkage and selection operator (LASSO) analysis was used to construct the multi-URG signature in the training set (METABRIC). Next, we evaluated and validated the signature in the test set (GSE58812). Finally, we evaluated the immune-related characteristics to explore the mechanism.

Results: We identified four clusters with significantly different immune signatures in TNBC based on URGs. Then, we developed an 11-URG signature with good performance for patients with TNBC. According to the 11-URG signature, TNBC patients can be classified into a high-risk group and a low-risk group with significantly different overall survival. The predictive ability of this 11-URG signature was favorable in the test set. Moreover, we constructed a nomogram comprising the risk score and clinicopathological characteristics with favorable predictive ability. All of the immune cells and immune-related pathways were higher in the low-risk group than in the high-risk group.

Conclusion: Our study indicated URGs might interact with the immune phenotype to influence the development of TNBC, which contributes to a further understanding of molecular mechanisms and the development of novel therapeutic targets for TNBC.
Type 2 and type 17 effector cells are increased in the duodenal mucosa but not peripheral blood of patients with functional dyspepsia
Authors: Burns Grace L. , Bruce Jessica K. , Minahan Kyra , Mathe Andrea , Fairlie Thomas , Cameron Raquel , Naudin Crystal , Nair Prema M. , Potter Michael D. E. , Irani Mudar Zand , Bollipo Steven , Foster Robert , Gan Lay T. , Shah Ayesha , Koloski Natasha A. , Foster Paul S. , Horvat Jay C. , Veysey Martin , Holtmann Gerald , Powell Nick , Walker Marjorie M. , Talley Nicholas J. , Keely Simon
Published: January 2023

Background

Functional dyspepsia is characterised by chronic symptoms of post-prandial distress or epigastric pain not associated with defined structural pathology. Increased peripheral gut-homing T cells have been previously identified in patients. To date, it is unknown if these T cells were antigen-experienced, or if a specific phenotype was associated with FD.

Objective

This study aimed to characterise T cell populations in the blood and duodenal mucosa of FD patients that may be implicated in disease pathophysiology.

Methods

We identified duodenal T cell populations from 23 controls and 49 Rome III FD patients by flow cytometry using a surface marker antibody panel. We also analysed T cell populations in peripheral blood from 37 controls and 61 patients. Where available, we examined the number of duodenal eosinophils in patients and controls.

Results

There was a shift in the duodenal T helper cell balance in FD patients compared to controls. For example, patients had increased duodenal mucosal Th2 populations in the effector (13.03 ± 16.11, 19.84 ± 15.51, p=0.038), central memory (23.75 ± 18.97, 37.52 ± 17.51, p=0.007) and effector memory (9.80±10.50 vs 20.53±14.15, p=0.001) populations. Th17 populations were also increased in the effector (31.74±24.73 vs 45.57±23.75, p=0.03) and effector memory (11.95±8.42 vs 18.44±15.63, p=0.027) subsets. Peripheral T cell populations were unchanged between FD and control.

Conclusion

Our findings identify an association between lymphocyte populations and FD, specifically a Th2 and Th17 signature in the duodenal mucosa. The presence of effector and memory cells suggest that the microinflammation in FD is antigen driven.
Type 2 cytokine genes as allergic asthma risk factors after viral bronchiolitis in early childhood
Authors: Dong Zihan , Myklebust Åsne , Johnsen Ingvild Bjellmo , Jartti Tuomas , Døllner Henrik , Risnes Kari , DeWan Andrew T.
Published: January 2023

Background

Genome-wide association studies of asthma have identified associations with variants in type-2 related genes. Also, specific interactions between genetic variants and viral bronchiolitis in the development of asthma has been suggested.

Objective

To conduct a gene-based analysis of genetic variants in type 2 cytokine related genes as risk factors for allergic asthma at school age, and further, to study their interaction with specific viral infections in early childhood.

Methods

A prospectively investigated cohort of children with previous bronchiolitis and controls came for follow-up at school age. The research visit, blinded to viral exposure, included detailed lung function tests, laboratory investigation, and questionnaires. Allergic asthma was defined as typical symptoms plus objective variable airway obstruction, in addition to laboratory verified atopy (elevated eosinophil count or sensitization to an allergen). Targeted and complete sequencing was performed for nine type 2 cytokine candidate genes: IL4, 5, 13, 25, 33 and 37, IL17RB, CRLF2 and TSLP.

Results

At follow-up, there were 109 children with genetic data, 91 with a history of bronchiolitis (46% respiratory syncytial virus, 24% human rhinovirus, 15% human metapneumovirus and 14% mixed viral etiology) and 18 without. The median age was 9.4 years (range 6-13) and 41 (38%) had laboratory verified atopy. Twenty-one children (19%) met the definition of allergic asthma. After adjusting for age, sex and five viral categories, IL33 achieved nominal significance (p = 0.017) for a positive association with allergic asthma development. In the gene-virus interaction analysis, the variant set in IL17RB demonstrated a nominally significant positive interaction with human metapneumovirus infection (p=0.05).

Conclusion

The results highlight the multifactorial nature of allergic asthma risk, with both viral infection and inherited genetic variants contributing to increasing risk. Results for IL33 and IL17RB were nominally significant and are potential candidate targets for designing therapeutics and early screening, but these results must be replicated in an independent study.
Establishment and verification a nomogram for predicting portal vein thrombosis presence among admitted cirrhotic patients
Authors: Liu Guang-hua , Lei Ping , Liao Chu-shu , Li Jing , Long Jiang-wen , Huan Xi-sha , Chen Jie
Published: January 2023

Background

Portal vein thrombosis (PVT) is an increasingly recognized complication of cirrhosis and possibly associated with mortality. This study aims to evaluate provoking factors for PVT, then establish a concise and efficient nomogram for predicting PVT presence among admitted cirrhotic patients.

Materials and methods

All cirrhotic patients admitted in Hunan Provincial People's Hospital between January 2010 and September 2020 were retrospectively reviewed, the clinical and laboratory data were collected. Multivariate logistic regression analysis and the least absolute shrinkage and selection operator regression method were used for screening the independent predictors and constructing the nomogram. The calibration curve was plotted to evaluate the consistent degree between observed outcomes and predicted probabilities. The area under the receiver operating characteristics curve was used to assess the discriminant performance. The decision curve analysis (DCA) was carried out to evaluate the benefits of nomogram.

Results

A total of 4,479 patients with cirrhosis were enrolled and 281 patients were identified with PVT. Smoking history, splenomegaly, esophagogastric varices, surgical history, red blood cell transfusion, and D-dimer were independent risk factors for PVT in cirrhosis. A nomogram was established with a good discrimination capacity and predictive efficiency with an the area under the curve (AUC) of 0.704 (95% CI: 0.664–0.745) in the training set and 0.685 (95% CI: 0.615–0.754) in the validation set. DCA suggested the net benefit of nomogram had a superior risk threshold probability.

Conclusion

A concise and efficient nomogram was established with good performance, which may aid clinical decision making and guide best treatment measures.
Sepsis caused by emphysematous pyelonephritis: A case report
Authors: Yang Zheng , Li Zhihui
Published: January 2023

Purpose

Emphysematous pyelonephritis (EPN) is a rare, life-threatening necrotizing renal parenchymal infection. It is most commonly reported in patients with poor glycemic control.

Patient concerns

We report the case of a 64-year-old woman who presented to the emergency room with fever and weakness over the last few days.

Diagnosis

After a series of tests in the diagnostic workup, the patient was diagnosed with emphysematous pyelonephritis and sepsis.

Intervention and outcome

She received conservative treatment with meropenem and symptomatic treatment, and the symptoms improved significantly.

Lessons

EPN can be reliably diagnosed using non-contrast abdominal CT imaging. The infection is most commonly caused by the Escherichia coli species, and a good curative effect can be achieved with early diagnosis and appropriate and timely treatment.
The molecular mechanism of ferroptosis and its role in COPD
Authors: Meng Dandan , Zhu Chengfeng , Jia Ruixue , Li Zongxin , Wang Wantao , Song Suhua
Published: January 2023

Ferroptosis, a new type of cell death, is mainly characterized by intracellular iron accumulation and lipid peroxidation. The complex regulatory network of iron metabolism, lipid metabolism, amino acid metabolism, p53-related signaling, and Nrf2-related signaling factors is involved in the entire process of ferroptosis. It has been reported that ferroptosis is involved in the pathogenesis of neurological diseases, cancer, and ischemia–reperfusion injury. Recent studies found that ferroptosis is closely related to the pathogenesis of COPD, which, to some extent, indicates that ferroptosis is a potential therapeutic target for COPD. This article mainly discusses the related mechanisms of ferroptosis, including metabolic regulation and signaling pathway regulation, with special attention to its role in the pathogenesis of COPD, aiming to provide safe and effective therapeutic targets for chronic airway inflammatory diseases.
Maternal diet associated with infants’ intestinal microbiota mediated by predominant long-chain fatty acid in breast milk
Authors: Xi Menglu , Na Xiaona , Ma Xia , Lan Hanglian , Sun Ting , Liu Wei-Hsien , Hung Weilian , Zhao Ai
Published: January 2023

Introduction

Long-chain fatty acids in breast milk are affected by the mother’s diet and play an important role in the growth, development, and immune construction of infants. This study aims to explore the correlation between maternal diet, breast milk fatty acids (FAs), and the infant intestinal flora.

Methods

We enrolled 56 paired mothers and their infants; both breast milk samples and infants’ fecal samples were collected to determine the long-chain FA content of breast milk by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS), and metagenomic technology was applied to determine the microbial composition of infant feces. The maternal diet was also investigated using a 24-h dietary recall.

Results

The results indicated that the fat contribution rates of edible oils in the maternal diet are significantly positively correlated with the contents of certain long-chain fatty acids (C16:0, C18:1, C16:1, and C22:4) in breast milk, which mainly regulate the abundance of Lacticaseibacillus rhamnosus, Lacticaseibacillus fermentum, and Lacticaseibacillus paracasei in the infant gut. Through KEGG pathway analysis, our data revealed that the long-chain FAs in different groups of breast milk were significantly correlated with the pathways of biotin metabolism, glycerolipid metabolism, and starch and sucrose metabolism.

Discussion

The results of this study suggest a pathway in which the diets of lactating mothers may affect the composition of the infant intestinal microbiota by influencing breast milk FAs and then further regulating infant health.
Secondary metabolites of Alternaria: A comprehensive review of chemical diversity and pharmacological properties
Authors: Zhao Shiqin , Li Juan , Liu Jinping , Xiao Shaoyujia , Yang Sumei , Mei Jiahui , Ren Mengyao , Wu Shuzhe , Zhang Hongyuan , Yang Xiliang
Published: January 2023

Fungi are considered to be one of the wealthiest sources of bio-metabolites that can be employed for yielding novel biomedical agents. Alternaria, including parasitic, saprophytic, and endophytic species, is a kind of dark fungi that can produce a broad array of secondary metabolites (SMs) widely distributed in many ecosystems. These are categorized into polyketides, nitrogen-containing compounds, quinones, terpenes, and others based on the unique structural features of the metabolites. New natural products derived from Alternaria exhibit excellent bioactivities characterized by antibacterial, antitumor, antioxidative, phytotoxic, and enzyme inhibitory properties. Thus, the bio-metabolites of Alternaria species are significantly meaningful for pharmaceutical, industrial, biotechnological, and medicinal applications. To update the catalog of secondary metabolites synthesized by Alternaria fungi, 216 newly described metabolites isolated from Alternaria fungi were summarized with their diverse chemical structures, pharmacological activity, and possible biosynthetic pathway. In addition, possible insights, avenues, and challenges for future research and development of Alternaria are discussed.
Alterations of gut mycobiota profiles in intrahepatic cholangiocarcinoma
Authors: Zhang Lilong , Chen Chen , Chai Dongqi , Kuang Tianrui , Deng Wenhong , Wang Weixing
Published: January 2023

Objective

Intrahepatic cholangiocarcinoma (ICC) is a silent liver malignancy with an increasing incidence. Gut mycobiota plays a crucial role in benign liver diseases; however, its correlation with ICC remains elusive. This study aimed to elucidate fungal differences in patients with ICC compared to healthy controls.

Methods

The 40 fecal samples from 23 ICC patients and 17 healthy controls were collected and analyzed using ITS2 rDNA sequencing. Obtaining the OTUs and combining effective grouping, we carried out the biodiversity and composition of the fungi, as well as FUNGuild functional annotation.

Results

Our results revealed the presence of intestinal fungal dysbiosis with significant enrichment of opportunistic pathogenic fungi such as Candida and C. albicans, and significant depletion of the beneficial fungus Saccharomyces cerevisiae in ICC patients compared with healthy controls. Alpha-diversity analysis demonstrated that patients with ICC showed decreased fungal diversity compared to healthy controls. Beta diversity analysis indicated that the two groups exhibited significant segregated clustering. Besides, C. albicans was found to be significantly more abundant in the ICC patients with TNM stage III-IV than those with stage I-II. The FUNGuild functional classification predicted that pathotrophs were the most abundant taxon in the ICC group, well above their abundance in healthy controls.

Conclusion

This study indicates that dysbiosis of the fecal mycobiome might be involved in ICC development. Further research into gut fungi may contribute to new therapeutic options for ICC patients.
Microbial metabolites indole derivatives sensitize mice to D-GalN/LPS induced-acute liver failure via the Tlr2/NF-κB pathway
Authors: Zhou Ziyuan , Wang Baohong , Pan Xiaxia , Lv Jiawen , Lou Zhuoqi , Han Yuqiu , Yao Yuanyuan , Chen Jun , Wang Qiangqiang , Li Lanjuan
Published: January 2023

Introduction

Acute liver failure (ALF) is a clinical condition with many causes, fast progression, and a poor prognosis. Previous research has indicated that microbial factors have a role in ALF, but a clear picture has yet to emerge.

Methods

To investigate the specific involvement of microbial metabolites in ALF development, we pretreated D-GalN/LPS-induced ALF mice with indole derivatives, an influential class of gut microbial metabolites.

Results

Contrary to their typical role as anti-inflammatory agents in the host, indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and indolepropionic acid (IPA) gavage sensitize mice to D-GalN/LPS-induced-ALF with a rapid rise in serum transaminases and histologic lesion. For a clearer picture, we performed comprehensive analysis for the IAA therapy. IAA markedly amplified inflammatory response and cellular damage. The transcriptome analysis indicated the participation of the TNF-α/NF-κB signaling pathway. The structure of gut microbiota in ileum and the expression of Toll-like receptor 2 (Tlr2) in the liver were also significantly changed.

Discussion

In conclusion, IAA pretreatment can exacerbate D-GalN/LPS-induced ALF via probable Tlr2/NF-κB pathway involvement and ileac dysbiosis characterized by enriched gram-positive genus with potential pathogenesis. Microbial metabolites IAA may aggravate individual susceptibility to D-GalN/LPS-induced ALF. Further investigation of the underlying mechanism is needed, and intervention with indole derivatives and related commensal species should be undertaken with caution.
Effect of Endosymbiotic Bacteria on Fungal Resistance Toward Heavy Metals
Authors: Lupini Simone , Peña-Bahamonde Janire , Bonito Gregory , Rodrigues Debora F.
Published: January 2023

Most studies on metal removal or tolerance by fungi or bacteria focus on single isolates, without taking into consideration that some fungi in nature may be colonized by endobacteria. To address this knowledge gap, we investigated the tolerance and removal of diverse metals with two fungal species: Linnemannia elongata containing Burkholderia-related endobacteria and Benniella erionia containing Mollicute-related endobacteria. Isogenic lines of both species were generated with antibiotic treatments to remove their respective endobacteria. Experiments involved comparing the isogenic lines and wild type fungi in relation to the minimum inhibitory concentration for the metals, the fungal ability to remove these different metals via atomic adsorption spectroscopy, and the interaction of the metals with specific functional groups of the fungi and fungi-bacteria to determine the role of the bacteria via attenuated total reflection fourier transformed infrared (ATR-FTIR). Finally, we determined the influence of different metal concentrations, associated with moderate and high fungal growth inhibition, on the presence of the endobacteria inside the fungal mycelium via quantitative real-time PCR. Results showed that the presence of the endosymbiont increased B. erionia resistance to Mn2+ and increased the removal of Fe2+ compared to isogenic lines. The absence of the endosymbiont in L. elongata increased the fungal resistance toward Fe2+ and improved the removal of Fe2+. Furthermore, when the bacterial endosymbiont was present in L. elongata, a decrease in the fungal resistance to Ca2+, Fe2+, and Cr6+was noticeable. In the ATR-FTIR analysis, we determined that C-H and C = O were the major functional groups affected by the presence of Cu2+, Mn2+, and Fe2+ for L. elongata and in the presence of Cu2+ and Ca2+ for B. eronia. It is noteworthy that the highest concentration of Pb2+ led to the loss of endobacteria in both L. elongata and B. eronia, while the other metals generally increased the concentration of endosymbionts inside the fungal mycelium. From these results, we concluded that bacterial endosymbionts of fungi can play a fundamental role in fungal resistance to metals. This study provides the first step toward a greater understanding of symbiotic interactions between bacteria and fungi in relation to metal tolerance and remediation.
Effect of chemical modifications of tannins on their antimicrobial and antibiofilm effect against Gram-negative and Gram-positive bacteria
Authors: Villanueva Xabier , Zhen Lili , Ares José Nunez , Vackier Thijs , Lange Heiko , Crestini Claudia , Steenackers Hans P.
Published: January 2023

Background

Tannins have demonstrated antibacterial and antibiofilm activity, but there are still unknown aspects on how the chemical properties of tannins affect their biological properties. We are interested in understanding how to modulate the antibiofilm activity of tannins and in delineating the relationship between chemical determinants and antibiofilm activity.

Materials and methods

The effect of five different naturally acquired tannins and their chemical derivatives on biofilm formation and planktonic growth of Salmonella Typhimurium, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus was determined in the Calgary biofilm device.

Results

Most of the unmodified tannins exhibited specific antibiofilm activity against the assayed bacteria. The chemical modifications were found to alter the antibiofilm activity level and spectrum of the tannins. A positive charge introduced by derivatization with higher amounts of ammonium groups shifted the anti-biofilm spectrum toward Gram-negative bacteria, and derivatization with lower amounts of ammonium groups and acidifying derivatization shifted the spectrum toward Gram-positive bacteria. Furthermore, the quantity of phenolic OH-groups per molecule was found to have a weak impact on the anti-biofilm activity of the tannins.

Conclusion

We were able to modulate the antibiofilm activity of several tannins by specific chemical modifications, providing a first approach for fine tuning of their activity and antibacterial spectrum.
TSPAN4 is a prognostic and immune target in Glioblastoma multiforme
Authors: Zheng Yue , Lang Yuheng , Qi Bingcai , Wang Yuchao , Gao Wenqing , Li Tong
Published: January 2023

Background: Atherosclerosis can impact cancer progression due to the cholesterol and calcium metabolism, illustrating the links between atherosclerosis and cancer metastasis. Tetraspanin 4 (TSPAN4) may help understand migrasomes in diseases and provide novel targets for treatment.

Methods: TSPAN4 expression in atherosclerosis Gene Expression Omnibus (EO) dataset and multiple omics data were explored, such as enriched pathways analysis, protein-protein interaction analysis, immune subtypes as well as diagnostic and prognostic value in pan-cancer. The relationship between Glioblastoma multiforme (GBM) and TSPAN4 was further investigated.

Results: Compared to control, TSPAN4 expression was upregulated in foam cells from patients with atherosclerosis and survival analysis demonstrated high TSPAN4 expression contributes to poor prognosis. TSPAN4 expression differs significantly in immune subtypes of cancers, which can be a diagnostic and prognostic target of cancers due to the high accuracy. Overall survival analysis of subgroups demonstrated that higher TSPAN4 expression had a worse prognosis and the univariate analysis and multivariate analysis demonstrated age, TSPAN4 expression, WHO grade, IDH status and histological types were independent risk factors of Glioblastoma multiforme.

Conclusion: The TSPAN4 expression was associated with atherosclerosis progression and pan-cancer, especially in Glioblastoma multiforme and GBMLGG. Therefore, TSPAN4 may serve as a potential biomarker and the crosstalk between atherosclerosis and tumor progression. The results are not fully validated and further studies are still needed to validate in vivo and in vitro.
Nicotinamide as potential biomarker for Alzheimer’s disease: A translational study based on metabolomics
Authors: Dalmasso María C. , Arán Martín , Galeano Pablo , Perin Silvina , Giavalisco Patrick , Martino Adami Pamela V. , Novack Gisela V. , Castaño Eduardo M. , Cuello A. Claudio , Scherer Martin , Maier Wolfgang , Wagner Michael , Riedel-Heller Steffi , Ramirez Alfredo , Morelli Laura
Published: January 2023

Introduction: The metabolic routes altered in Alzheimer's disease (AD) brain are poorly understood. As the metabolic pathways are evolutionarily conserved, the metabolic profiles carried out in animal models of AD could be directly translated into human studies.

Methods: We performed untargeted Nuclear Magnetic Resonance metabolomics in hippocampus of McGill-R-Thy1-APP transgenic (Tg) rats, a model of AD-like cerebral amyloidosis and the translational potential of these findings was assessed by targeted Gas Chromatography-Electron Impact-Mass Spectrometry in plasma of participants in the German longitudinal cohort AgeCoDe.

Results: In rat hippocampus 26 metabolites were identified. Of these 26 metabolites, nine showed differences between rat genotypes that were nominally significant. Two of them presented partial least square-discriminant analysis (PLS-DA) loadings with the larger absolute weights and the highest Variable Importance in Projection (VIP) scores and were specifically assigned to nicotinamide adenine dinucleotide (NAD) and nicotinamide (Nam). NAD levels were significantly decreased in Tg rat brains as compared to controls. In agreement with these results, plasma of AD patients showed significantly reduced levels of Nam in respect to cognitively normal participants. In addition, high plasma levels of Nam showed a 27% risk reduction of progressing to AD dementia within the following 2.5 years, this hazard ratio is lost afterwards.

Discussion: To our knowledge, this is the first report showing that a decrease of Nam plasma levels is observed couple of years before conversion to AD, thereby suggesting its potential use as biomarker for AD progression.
Decreased default mode network functional connectivity with visual processing regions as potential biomarkers for delayed neurocognitive recovery: A resting-state fMRI study and machine-learning analysis
Authors: Jiang Zhaoshun , Cai Yuxi , Liu Songbin , Ye Pei , Yang Yifeng , Lin Guangwu , Li Shihong , Xu Yan , Zheng Yangjing , Bao Zhijun , Nie Shengdong , Gu Weidong
Published: January 2023

Objectives

The abnormal functional connectivity (FC) pattern of default mode network (DMN) may be key markers for early identification of various cognitive disorders. However, the whole-brain FC changes of DMN in delayed neurocognitive recovery (DNR) are still unclear. Our study was aimed at exploring the whole-brain FC patterns of all regions in DMN and the potential features as biomarkers for the prediction of DNR using machine-learning algorithms.

Methods

Resting-state functional magnetic resonance imaging (fMRI) was conducted before surgery on 74 patients undergoing non-cardiac surgery. Seed-based whole-brain FC with 18 core regions located in the DMN was performed, and FC features that were statistically different between the DNR and non-DNR patients after false discovery correction were extracted. Afterward, based on the extracted FC features, machine-learning algorithms such as support vector machine, logistic regression, decision tree, and random forest were established to recognize DNR. The machine learning experiment procedure mainly included three following steps: feature standardization, parameter adjustment, and performance comparison. Finally, independent testing was conducted to validate the established prediction model. The algorithm performance was evaluated by a permutation test.

Results

We found significantly decreased DMN connectivity with the brain regions involved in visual processing in DNR patients than in non-DNR patients. The best result was obtained from the random forest algorithm based on the 20 decision trees (estimators). The random forest model achieved the accuracy, sensitivity, and specificity of 84.0, 63.1, and 89.5%, respectively. The area under the receiver operating characteristic curve of the classifier reached 86.4%. The feature that contributed the most to the random forest model was the FC between the left retrosplenial cortex/posterior cingulate cortex and left precuneus.

Conclusion

The decreased FC of DMN with regions involved in visual processing might be effective markers for the prediction of DNR and could provide new insights into the neural mechanisms of DNR.

Clinical Trial Registration

: Chinese Clinical Trial Registry, ChiCTR-DCD-15006096.
The distinct role of orbitofrontal and medial prefrontal cortex in encoding impulsive choices in an animal model of attention deficit hyperactivity disorder
Authors: Cao Aihua , Hong Dandan , Che Chao , Yu Xiaoxiao , Cai Zhifeng , Yang Xiaofan , Zhang Di , Yu Ping
Published: January 2023

Attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder affecting up to 5% of children worldwide. The lack of understanding of ADHD etiology prevented the development of effective treatment for the disease. Here, using in vivo electrophysiology recordings, we have recorded and analyzed the neuronal encoding of delay discounting behavior in prefrontal and orbitofrontal cortex of spontaneously hypertensive rat (SHR). We found that in the presence of rewards, neurons in the orbitofrontal cortex (OFC) were activated regardless to the value of the rewards and OFC neurons in SHR exhibited significantly higher rates of neuronal discharging towards the presence of rewards. While in the medial prefrontal cortex (mPFC), neurons of SHR responded similarly in the presence of large rewards compared with control rats whereas they displayed higher firing rates towards smaller rewards. In addition, the reward-predicting neurons in the OFC encodes for value of rewards in control animals and they were strongly activated upon receiving a small immediate reinforcer in the SHR whereas the reward-predicting neurons in the mPFC neurons generally did not respond to the value of the rewards. Our study characterized the neuronal discharging patterns of OFC and mPFC neurons in the SHR and the control animals and provided novel insights for further understanding the neuronal basis of ADHD pathology.