bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-13 Alleviates Cardiomyocyte Apoptosis by Improving Fatty Acid Oxidation in Mitochondria
Authors: Guo Xiaoyu , Hong Ting , Zhang Shen , Wei Yazhong , Jin Haizhen , Miao Qing , Wang Kai , Zhou Miao , Wang Chong , He Bin
Published: September 2021

Sepsis-induced cardiac injury (SIC) is one of the most common complications in the intensive care unit (ICU) with high morbidity and mortality. Mitochondrial dysfunction is one of the main reasons for SIC, and Interleukin-13 (IL-13) is a master regulator of mitochondria biogenesis. The aim of the present study was to investigate the role of IL-13 in SIC and explore the underlying mechanism. It was found that reactive oxygen species (ROS) production and apoptosis were significantly increased in lipopolysaccharide (LPS)-stimulated primary cardiomyocytes, which was accompanied with obvious mitochondria dysfunction. The results of RNA-sequencing (RNA-seq), mitochondrial membrane potential, fatty acid uptake and oxidation rate suggested that treatment with IL-13 could restore the function and morphology of mitochondria, indicating that it played an important role in protecting septic cardiomyocytes. These findings demonstrated that IL-13 alleviated sepsis-induced cardiac inflammation and apoptosis by improving mitochondrial fatty acid uptake and oxidation, suggesting that IL-13 may prove to be a potential promising target for SIC treatment.
Benzopyrazine-Based Small Molecule Inhibitors As Trypanocidal and Leishmanicidal Agents: Green Synthesis, In Vitro, and In Silico Evaluations
Authors: Rock Jonathan , Garcia Daniel , Espino Omar , Shetu Shaila A. , Chan-Bacab Manuel J. , Moo-Puc Rosa , Patel Navin B. , Rivera Gildardo , Bandyopadhyay Debasish
Published: September 2021

World Health Organization (WHO) identified twenty tropical disease categories as neglected tropical diseases (NTDs)1. Chagas’ disease (also known as American trypanosomiasis) and leishmaniasis are two major classes of NTDs. The total number of mortality, morbidity, and disability attributed each year due to these two categories of diseases in magnitudes is much higher than the so-called elite diseases like cancer, diabetes, AIDS, cardiovascular and neurodegenerative diseases. Impoverished communities around the world are the major victim of NTDs. The development of new and novel drugs in the battle against Chagas’ disease and leishmaniasis is highly anticipated. An easy and straightforward on-water green access to synthesize benzopyrazines is reported. This ultrasound-assisted procedure does not require any catalyst/support/additive/hazardous solvents and maintains a high atom economy. A series of eleven benzopyrazines has been synthesized, and most of the synthesized compounds possess the drug-likeness following Lipinski’s “Rule of 5”. Benzopyrazines 3 and 4 demonstrated moderate leishmanicidal activity against L. mexicana (M378) strain. The selective lead compound 1 showed good leishmanicidal, and trypanocidal activities (in vitro) against both L. mexicana (M378) and T. cruzi (NINOA) strains compared to the standard controls. The in vitro trypanocidal and leishmanicidal activities of the lead compound 1 have been validated by molecular docking studies against four biomolecular drug targets viz. T. cruzi histidyl-tRNA synthetase, T. cruzi trans-sialidase, leishmanial rRNA A-site, and leishmania major N-myristoyl transferase.
The Influence of the Chemical Potential on Defects and Function of Perovskites in Catalysis
Authors: Koch Gregor , Hävecker Michael , Kube Pierre , Tarasov Andrey , Schlögl Robert , Trunschke Annette
Published: September 2021

A Sm-deficient Sm0.96MnO3 perovskite was prepared on a gram scale to investigate the influence of the chemical potential of the gas phase on the defect concentration, the oxidation states of the metals and the nature of the oxygen species at the surface. The oxide was treated at 450°C in nitrogen, synthetic air, oxygen, water vapor or CO and investigated for its properties as a catalyst in the oxidative dehydrogenation of propane both before and after treatment. After treatment in water vapor, but especially after treatment with CO, increased selectivity to propene was observed, but only when water vapor was added to the reaction gas. As shown by XRD, SEM, EDX and XRF, the bulk structure of the oxide remained stable under all conditions. In contrast, the surface underwent strong changes. This was shown by AP-XPS and AP-NEXAFS measurements in the presence of the different gas atmospheres at elevated temperatures. The treatment with CO caused a partial reduction of the metals at the surface, leading to changes in the charge of the cations, which was compensated by an increased concentration of oxygen defects. Based on the present experiments, the influence of defects and concentration of electrophilic oxygen species at the catalyst surface on the selectivity in propane oxidation is discussed.
Declining Abundance of Coccinellidae (Coleoptera) Among Crop and Prairie Habitats of Eastern South Dakota, USA
Authors: Hesler Louis S. , Beckendorf Eric A.
Published: September 2021

Lady (= ladybird) beetles (Coleoptera: Coccinellidae) provide agroecosystem services as major predators of aphids and other pests of field crops. Several native coccinellids in North America have declined in association with the introduction of invasive species of lady beetles. In particular, populations of three native species declined drastically (Coccinella transversoguttata richardsoni) or effectively disappeared (Coccinella novemnotata, Adalia bipunctata) from agricultural landscapes in eastern South Dakota, U.S.A., following establishment of an invasive coccinellid (Coccinella septempunctata) in the 1980s. Since then, two other non-native coccinellids (Harmonia axyridisandHippodamia variegata) have established in eastern South Dakota, but long-term analysis of their impact on the aphidophagous coccinellid guild is lacking. This paper summarizes long-term results from 14 years (2007–2020) of sampling coccinellids by sweepnet and timed searches in five field crops and restored prairie in eastern South Dakota. In all, 17,338 aphidophagous coccinellids comprising 10 species were sampled. Two invasive species (Coc. septempunctata, Har. axyridis) were the third- and fourth-most abundant species, respectively. The seven most abundant species constituted 99% of all coccinellids sampled and were recorded from all six habitats. However, coccinellid species ranged considerably in their evenness of habitat use, resulting in differences in rank abundance among habitats. Coccinellid assemblages were similar for alfalfa and winter wheat, but not for other habitats, which possessed distinct coccinellid assemblages based on rank abundance. Annual abundance of coccinellids varied considerably within habitats, but declining trends were evident from significant negative regressions in annual abundance for adult and immature coccinellids in corn and adults in soybean. As a group, native adult coccinellids showed a significant declining trend in corn but not in other habitats, whereas trends for non-native adult coccinellids were non-significant in all habitats. Sample rates of coccinellids in alfalfa, spring grains, and corn in this study were 74, 26, and 6%, respectively, compared to that of a previous study from the region, further indicating substantial decreases in coccinellid abundance. Possible explanations and implications for observed patterns in coccinellid diversity and individual species abundances in field crops and restored prairie of eastern South Dakota are discussed with respect to prey, agronomic trends, and landscape factors.
Endothelial to Mesenchymal Transition: An Insight in Atherosclerosis
Authors: Huang Qingyan , Gan Yuhong , Yu Zhikang , Wu Heming , Zhong Zhixiong
Published: September 2021

Atherosclerosis is a fundamental disease of the cardiovascular system that leads to high morbidity and mortality worldwide. The endothelium is the first protective barrier in atherosclerosis. Endothelial cells have the potential to be transformed into mesenchymal cells, in a process termed endothelial to mesenchymal transition (EndMT). On the one hand, EndMT is known to contribute to atherosclerosis by inducing a number of phenotypes ranging from endothelial cell dysfunction to plaque formation. On the other hand, risk factors for atherosclerosis can lead to EndMT. A substantial body of evidence has suggested that EndMT induces the development of atherosclerosis; therefore, a deeper understanding of the molecular mechanisms underlying EndMT in atherosclerosis might provide insights to reverse this condition.
A Novel Diagnostic Predictive Model for Idiopathic Short Stature in Children
Authors: Yuan Jinghong , Du Zhi , Wu Zhiwen , Yang Yanqin , Cheng Xigao , Liu Xijuan , Jia Jingyu
Published: September 2021

Objective

Idiopathic short stature (ISS), an endocrine-related disease, is difficult to diagnose. Previous studies have shown that many children with some inflammation-related diseases often have short stature, but whether inflammation is the underlying mechanism of ISS has not been studied. Here, we attempt to explore the role of inflammation in the occurrence and development of ISS and to demonstrate an available clinical diagnostic model of ISS.

Methods

Frozen serum samples were collected from ISS patients (n = 4) and control individuals (n = 4). Isobaric tags for relative and absolute quantitation (iTRAQ) combined with LC-MS/MS analysis were applied to quantitative proteomics analysis. To assess clusters of potentially interacting proteins, functional enrichment (GO and KEGG) and protein-protein interaction network analyses were performed, and the crucial proteins were detected by Molecular Complex Detection (MCODE). Furthermore, serum levels of two selected proteins were measured by ELISA between ISS patients (n = 80) and controls (n = 80). In addition, experimentsin vitrowere used to further explore the effects of crucial proteins on endochondral ossification.

Results

A total of 437 proteins were quantified, and 84 DEPs (60 upregulated and 24 downregulated) were identified between patients with ISS and controls. Functional enrichment analysis showed that the DEPs were primarily enriched in blood microparticle, acute inflammatory response, protein activation cascade, collagen-containing extracellular matrix, platelet degranulation, etc. According to the results of top 10 fold change DEPs and MCODE analysis, C1QA and C1QB were selected to further experiment. The expression levels of C1QA and C1QB were validated in serum samples. Based on the logistic regression analysis and ROC curve analysis, we constructed a novel diagnostic model by serum levels of C1QA and C1QB with a specificity of 91.2% and a sensitivity of 75% (AUC = 0.900, p <0.001). Finally, the western blotting analysis confirmed the expression levels of OCN, OPN, RUNX2, and Collagen X were downregulated in chondrocytes, and the outcome of Collagen II was upregulated.

Conclusion

Our study is the first to demonstrate the significant role of inflammation in the development of ISS. In addition, we identify C1QA and C1QB as novel serum biomarkers for the diagnosis of ISS.
Transcriptome Analysis of Ostrinia furnacalis Female Pheromone Gland: Esters Biosynthesis and Requirement for Mating Success
Authors: Yao Shuangyan , Zhou Shuai , Li Xiang , Liu Xiaoguang , Zhao Wenli , Wei Jizhen , Du Mengfang , An Shiheng
Published: September 2021

Female moths use sex pheromones to attract males, and corresponding regulatory mechanism underlying sex pheromone biosynthesis is species-dependent. However, the detailed mechanism involved in sex pheromone biosynthesis in Ostrinia furnacalis has not yet been fully addressed. In the present study, transcriptome sequencing of O. furnacalis pheromone glands screened a serials of candidate genes involved in sex pheromone biosynthesis. Our analysis showed that sex pheromone release in O. furnacalis females arrives its peak at the 2nd scotophase, consistent with its mating behavior. Pheromone biosynthesis-activating neuropeptide (PBAN) was confirmed to regulate sex pheromone biosynthesis, and Ca2+ is the secondary messenger of PBAN signaling in O. furnacalis. The functional analysis of candidate genes demonstrated that the decreased mRNA levels or activities of calcineurin (CaN) and acetyl-CoA carboxylase (ACC) led to significant decrease in sex pheromone production and female capability to attract males, as demonstrated by RNAi-mediated knockdown and pharmacological inhibitor assay. Most importantly, the activities of CaN and ACC depend on the activation of PBAN/PBANR/Ca2+. Furthermore, fatty-acyl reductase 14 was involved in PBAN-mediated sex pheromone biosynthesis. Altogether, our results demonstrated that PBAN regulates sex pheromone biosynthesis through PBANR/Ca2+/CaN/ACC pathway to promote sex pheromone biosynthesis in O. furnacalis and provided a reference for non-model organism to study neuropeptide signal transduction.
An Ensemble Prediction System Based on Artificial Neural Networks and Deep Learning Methods for Deterministic and Probabilistic Carbon Price Forecasting
Authors: Yang Yi , Guo Honggang , Jin Yu , Song Aiyi
Published: September 2021

Carbon price prediction is important for decreasing greenhouse gas emissions and coping with climate change. At present, a variety of models are widely used to predict irregular, nonlinear, and nonstationary carbon price series. However, these models ignore the importance of feature extraction and the inherent defects of using a single model; thus, accurate and stable prediction of carbon prices by relevant industry practitioners and the government is still a huge challenge. This research proposes an ensemble prediction system (EPS) that includes improved data feature extraction technology, three prediction submodels (GBiLSTM, CNN, and ELM), and a multiobjective optimization algorithm weighting strategy. At the same time, based on the best fitting distribution of the prediction error of the EPS, the carbon price prediction interval is constructed as a way to explore its uncertainty. More specifically, EPS integrates the advantages of various submodels and provides more accurate point prediction results; the distribution function based on point prediction error is used to establish the prediction interval of carbon prices and to mine and analyze the volatility characteristics of carbon prices. Numerical simulation of the historical data available for three carbon price markets is also conducted. The experimental results show that the ensemble prediction system can provide more effective and stable carbon price forecasting information and that it can provide valuable suggestions that enterprise managers and governments can use to improve the carbon price market.
Integrative Analysis Reveals Potentially Functional N6-Methylandenosine-Related Long Noncoding RNAs in Colon Adenocarcinoma
Authors: Tan Xinjie , Li Qian , Zhang Qinya , Fan Gang , Liu Zhuo , Zhou Kunyan
Published: September 2021

N6-methyladenosine (m6A) is one of the most prevalent RNA modifications in mRNA and non-coding RNA. In this study, we identified 10 upregulated m6A regulators at both mRNA and protein levels, and 2,479 m6A-related lncRNAs. Moreover, the m6A-related long noncoding RNAs (lncRNAs) could clearly stratify the colon adenocarcinoma (COAD) samples into three subtypes. The subtype 2 had nearly 40% of samples with microsatellite instability (MSI), significantly higher than the two other subtypes. In accordance with this finding, the inflammatory response-related pathways were highly activated in this subtype. The subtype-3 had a shorter overall survival and a higher proportion of patients with advanced stage than subtypes 1 and 2 (p-value < 0.05). Pathway analysis suggested that the energy metabolism-related pathways might be aberrantly activated in subtype 3. In addition, we observed that most of the m6A readers and m6A-related lncRNAs were upregulated in subtype 3, suggesting that the m6A readers and the m6A-related lncRNAs might be associated with metabolic reprogramming and unfavorable outcome in COAD. Among the m6A-related lncRNAs in subtype 3, four were predicted as prognostically relevant. Functional inference suggested that CTD-3184A7.4, RP11-458F8.4, and RP11-108L7.15 were positively correlated with the energy metabolism-related pathways, further suggesting that these lncRNAs might be involved in energy metabolism-related pathways. In summary, we conducted a systematic data analysis to identify the key m6A regulators and m6A-related lncRNAs, and evaluated their clinical and functional importance in COAD, which may provide important evidences for further m6A-related researches.
Synergistic Protective Effect of Konjac Mannan Oligosaccharides and Bacillus subtilis on Intestinal Epithelial Barrier Dysfunction in Caco-2 Cell Model and Mice Model of Lipopolysaccharide Stimulation
Authors: Chen Lupeng , Zhang Shuai , Wu Shi , Ren Zhuqing , Liu Guoquan , Wu Jian
Published: September 2021

As the first line of defense against intestinal bacteria and toxins, intestinal epithelial cells are always exposed to bacteria or lipopolysaccharide (LPS), whereas pathogenic bacteria or LPS can cause intestinal epithelial cell damage. Previous studies have shown that konjac mannan oligosaccharides (KMOS) have a positive effect on maintaining intestinal integrity, and Bacillus subtilis (BS) can promote the barrier effect of the intestine. However, it is still unknown whether KMOS and BS have a synergistic protective effect on the intestines. In this study, we used the LPS-induced Caco-2 cell injury model and mouse intestinal injury model to study the synergistic effects of KMOS and BS. Compared with KMOS or BS alone, co-treatment with KMOS and BS significantly enhanced the activity and antioxidant capacity of Caco-2 cell, protected mouse liver and ileum from LPS-induced oxidative damage, and repaired tight junction and mucus barrier damage by up-regulating the expression of Claudin-1, ZO-1 and MUC-2. Our results demonstrate that the combination of KMOS and BS has a synergistic repair effect on inflammatory and oxidative damage of Caco-2 cells and aIIeviates LPS-induced acute intestinal injury in mice.
Potential Cross-Reactive Immunity to COVID-19 Infection in Individuals With Laboratory-Confirmed MERS-CoV Infection: A National Retrospective Cohort Study From Saudi Arabia
Authors: Khan Anas A. , Alahmari Ahmed A. , Almuzaini Yasir , Alamri Fahad , Alsofayan Yousef Mohammad , Aburas Alhanouf , Al-Muhsen Saleh , Van Kerkhove Maria , Yezli Saber , Ciottone Gregory R. , Assiri Abdullah M. , Jokhdar Hani A.
Published: September 2021

Background

A growing number of experiments have suggested potential cross-reactive immunity between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and previous human coronaviruses. We conducted the present retrospective cohort study to investigate the relationship between previous Middle East respiratory syndrome-coronavirus (MERS-CoV) infection and the risk of SARS-CoV-2 infection as well as the relationship between previous MERS-CoV and COVID-19-related hospitalization and mortality.

Methods

Starting in March 2020, we prospectively followed two groups of individuals who tested negative for COVID-19 infection. The first group had a previously confirmed MERS-CoV infection, which was compared to a control group of MERS-negative individuals. The studied cohort was then followed until November 2020 to track evidence of contracting COVID-19 infection.

Findings

A total of 82 (24%) MERS-positive and 260 (31%) MERS-negative individuals had COVID-19 infection. Patients in the MERS-positive group had a lower risk of COVID-19 infection than those in the MERS-negative group (Risk ratio [RR] 0.696, 95% confidence interval [CI] 0.522-0.929; p =0.014). The risk of COVID-19-related hospitalization in the MERS-positive group was significantly higher (RR 4.036, 95% CI 1.705-9.555; p =0.002). The case fatality rate (CFR) from COVID-19 was 4.9% in the MERS-positive group and 1.2% in the MERS-negative group (p =0.038). The MERS-positive group had a higher risk of death than the MERS-negative group (RR 6.222, 95% CI 1.342-28.839; p =0.019). However, the risk of mortality was similar between the two groups when death was adjusted for age (p =0.068) and age and sex (p =0.057). After controlling for all the independent variables, only healthcare worker occupation and >1 comorbidity were independent predictors of SARS-CoV-2 infection.

Interpretation

Individuals with previous MERS-CoV infection can exhibit a cross-reactive immune response to SARS-CoV-2 infection. Our study demonstrated that patients with MERS-CoV infection had higher risks of COVID-19-related hospitalization and death than MERS-negative individuals.
Group Size of Indo-Pacific Humpback Dolphins (Sousa chinensis): An Examination of Methodological and Biogeographical Variances
Authors: Liu Mingming , Lin Mingli , Tang Xiaoming , Dong Lijun , Zhang Peijun , Lusseau David , Li Songhai
Published: September 2021

Observer-based counts and photo-identification are two well-established methods with an extensive use in cetacean studies. Using these two methods, group size has been widely reported, especially for small dolphins. Both methods may come with potential errors in estimating the group size, yet there is still a lack of comparison between both methods over a broad range of group size. Particularly, biogeographical variances in group size estimates were often mixed with methodological variances, making it difficult to compare estimates from different geographic regions. Here, group size estimates of a small, shallow-water, and near-shore delphinid species, Indo-Pacific humpback dolphins (Sousa chinensis), were simultaneously sampled using observer-based counts and photo-identification at three regions in the northern South China Sea. Data showed that dolphin group size from two methods were highly variable and associated with sampling regions. Generalized linear mixed models (GLMMs) indicated that dolphin group size significantly differed among regions. Statistical examinations further demonstrated dolphin group size could be affected by a complex combination of methodological and biogeographical variances. A common hurdle to examine potential factors influencing the estimation process is the inability to know the true group size at each sample. Therefore, other methods that could generate comparable estimates to represent true group size are warranted in future studies. To conclude, our findings present a better understanding of methodological and biogeographical variances in group size estimates of humpback dolphins, and help yield more robust abundance and density estimation for these vulnerable animals.
Deterministic Transfer of Large-Scale β-Phase Arsenic on Fiber End Cap for Near-Infrared Ultrafast Pulse Generation
Authors: Yu Qiang , Chen Cheng , Guo Kun , Deng Haiqin , Yi Tianan , Zhang Yan , Su Wei , Wu Jian , Zhang Kai
Published: September 2021

Gray arsenic (β-phase) has aroused great attention in photonics and electronics applications, as a novel family member of two-dimensional (2D) elemental crystals of group-VA. Here, β-phase arsenic (β-As) bulk crystals were synthesized via the chemical vapor transport (CVT) method. Meanwhile, large-scale β-As nanoflake was transformed using the polydimethylsiloxane (PDMS)-assisted dry transfer method and was placed on the end cap of optical fiber with high coverage over the core area. Moreover, the β-As was used as a saturable absorber in ytterbium-doped fiber ring cavity resonance, and we demonstrated near-infrared ultrafast pulse fiber laser with the central wavelength, repetition rate, and signal-to-noise ratio (SNR) of 1,037.3 nm, 0.6 MHz, and 67.7 dB, respectively. This research demonstrates a 2D material small area deterministic transfer method and promotes the potential application of group-VA crystals in near-infrared ultrafast laser generation.
A Unified Strength Model of Asphalt Mixture Considering Temperature Effect
Authors: Qian Guoping , Yang Hui , Li Xi , Yu Huanan , Gong Xiangbing , Zhou Hongyu
Published: September 2021

The strength characteristics of asphalt mixture is crucial for the design and construction of asphalt roads. A strength model considering the effect of temperature is presented in this paper based on unified strength theory (UST). Firstly, direct tensile tests, uniaxial compression tests and anti-shear property tests of asphalt mixture were carried out respectively at different temperatures. Key mechanical parameters were obtained, including tensile strength (σt), compressive strength (σc) and shear strength (τ0) at different temperatures. Besides, the temperature sensitivity of σt, σc and τ0 was systematically analyzed. The results showed that the UST parameters of tensile-compression strength ratio α and failure criterion parameter b have a linear relationship with temperature t. A theoretical model to describe strength characteristics with the temperature of asphalt mixture was developed finally. The developed model was validated via applicability analysis. and it will provide theoretical support for the study of strength characteristics of asphalt mixture and engineering practice.
Novel Rotational Combination Regimen of Skin Topicals Improves Facial Photoaging: Efficacy Demonstrated in Double-Blinded Clinical Trials and Laboratory Validation
Authors: DiNatale Lisa , Idkowiak-Baldys Jolanta , Zhuang Young , Gonzalez Anthony , Stephens Thomas J. , Jiang Lily I. , Li Weiping , Basson Rubinder , Bayat Ardeshir
Published: September 2021

Topical antiaging products are often a first-line intervention to counter visible signs of facial photoaging, aiming for sustained cosmetic improvement. However, prolonged application of a single active topical compound was observed clinically to lead to a plateau effect in improving facial photoaging. In view of this, we set out to reduce this effect systematically using a multi-tiered approach with laboratory evidence and clinical trials. The objective of the study was to evaluate the effects of active topical ingredients applied either alone, in combination, or in a rotational manner on modulation of facial photoaging. The study methodology included in vitro, organotypic, and ex vivo skin explants; in vivo biopsy study; as well as clinical trials. We demonstrate for the first time that a pair of known antiaging ingredients applied rotationally, on human dermal fibroblasts, maximized pro-collagen I production. Indeed, rotational treatment with retinol and phytol/glycolic acid (PGA) resulted in better efficacy than application of each active ingredient alone as shown by explants and in vivo biopsy study, with penetration of active ingredients confirmed by Raman spectroscopy. Furthermore, two split-face, randomized, double-blinded clinical trials were conducted, one for 12 months to compare treated vs. untreated and the other for 6 months followed by a 2-month regression to compare treated vs. commercially marketed products. In both studies, rotational regimen showed superior results to its matching comparison as assessed by clinical grading and image analysis of crow's feet wrinkles. In conclusion, rotational regimen using retinol and PGA is effective in treating facial photoaging signs with long-lasting benefits.
Relationships Between the Microbial Composition and the Geochemistry and Mineralogy of the Cobalt-Bearing Legacy Mine Tailings in Northeastern Ontario
Authors: Courchesne Brittaney , Schindler Michael , Mykytczuk Nadia C. S.
Published: September 2021

Mine tailings host dynamic biogeochemical processes that can mobilize a range of elements from the host material and release them into the environment through acidic, neutral, or alkaline mine drainage. Here we use a combination of mineralogical, geochemical, and microbiological techniques that provide a better understanding of biogeochemical processes within the surficial layers of neutral cobalt and arsenic-rich tailings material at Cobalt, ON, Canada. Tailings material within 30-cm depth profiles from three tailings sites (sites A, B, and C) were characterized for their mineralogical, chemical and microbial community compositions. The tailings material at all sites contains (sulf)arsenides (safflorite, arsenopyrite), and arsenates (erythrite and annabergite). Site A contained a higher and lower amount of (sulf)arsenides and arsenates than site B, respectively. Contrary to site A and B, site C depicted a distinct zoning with (sulf)arsenides found in the deeper reduced zone, and arsenates occurring in the shallow oxidized zone. Variations in the abundance of Co+As+Sb+Zn (Co#), Fe (Fe#), total S (S#), and average valence of As indicated differences in the mineralogical composition of the tailings material. For example, material with a high Co#, lo Fe# and high average valence of As commonly have a higher proportion of secondary arsenate to primary (sulf)arsenide minerals. Microbial community profiling indicated that the Cobalt tailings are primarily composed of Actinobacteria and Proteobacteria, and known N, S, Fe, methane, and possible As-cycling bacteria. The tailings from sites B and C had a larger abundance of Fe and S-cycling bacteria (e.g., Sulfurifustis and Thiobacillus), which are more abundant at greater depths, whereas the tailings of site A had a higher proportion of potential As-cycling and -resistant genera (e.g., Methylocystis and Sphingomonas). A multi-variate statistical analysis showed that (1) distinct site-specific groupings occur for the Co # vs. Fe #, Co# vs. S#’s and for the microbial community structure and (2) microbial communities are statistically highly correlated to depth, S#, Fe#, pH and the average valence of As. The variation in As valence correlated well with the abundance of N, S, Fe, and methane-cycling bacteria. The results of this study provide insights into the complex interplay between minerals containing the critical element cobalt, arsenic, and microbial community structure in the Cobalt Mining Camp tailings.
Potential Activities and Long Lifetimes of Organic Carbon-Degrading Extracellular Enzymes in Deep Subsurface Sediments of the Baltic Sea
Authors: Schmidt Jenna M. , Royalty Taylor M. , Lloyd Karen G. , Steen Andrew D.
Published: September 2021

Heterotrophic microorganisms in marine sediments produce extracellular enzymes to hydrolyze organic macromolecules, so their products can be transported inside the cell and used for energy and growth. Therefore, extracellular enzymes may mediate the fate of organic carbon in sediments. The Baltic Sea Basin is a primarily depositional environment with high potential for organic matter preservation. The potential activities of multiple organic carbon-degrading enzymes were measured in samples obtained by the International Ocean Discovery Program Expedition 347 from the Little Belt Strait, Denmark, core M0059C. Potential maximum hydrolysis rates (Vmax) were measured at depths down to 77.9mbsf for the following enzymes: alkaline phosphatase, β-d-xylosidase, β-d-cellobiohydrolase, N-acetyl-β-d-glucosaminidase, β-glucosidase, α-glucosidase, leucyl aminopeptidase, arginyl aminopeptidase, prolyl aminopeptidase, gingipain, and clostripain. Extracellular peptidase activities were detectable at depths shallower than 54.95mbsf, and alkaline phosphatase activity was detectable throughout the core, albeit against a relatively high activity in autoclaved sediments. β-glucosidase activities were detected above 30mbsf; however, activities of other glycosyl hydrolases (β-xylosidase, β-cellobiohydrolase, N-acetyl-β-glucosaminidase, and α-glucosidase) were generally indistinguishable from zero at all depths. These extracellular enzymes appear to be extremely stable: Among all enzymes, a median of 51.3% of enzyme activity was retained after autoclaving for an hour. We show that enzyme turnover times scale with the inverse of community metabolic rates, such that enzyme lifetimes in subsurface sediments, in which metabolic rates are very slow, are likely to be extraordinarily long. A back-of-the-envelope calculation suggests enzyme lifetimes are, at minimum, on the order of 230days, and may be substantially longer. These results lend empirical support to the hypothesis that a population of subsurface microbes persist by using extracellular enzymes to slowly metabolize old, highly degraded organic carbon.
Deep Investigating the Changes of Gut Microbiome and Its Correlation With the Shifts of Host Serum Metabolome Around Parturition in Sows
Authors: Fu Hao , He Maozhang , Wu Jinyuan , Zhou Yunyan , Ke Shanlin , Chen Zhe , Liu Qin , Liu Min , Jiang Hui , Huang Lusheng , Chen Congying
Published: September 2021

Parturition is a crucial event in the sow reproduction cycle, which accompanies by a series of physiological changes, including sex hormones, metabolism, and immunity. More and more studies have indicated the changes of the gut microbiota from pregnancy to parturition. However, what bacterial species and functional capacities of the gut microbiome are changed around parturition has been largely unknown, and the correlations between the changes of gut bacterial species and host metabolome were also uncovered. In this study, by combining 16S rRNA gene and shotgun metagenomic sequencing data, and the profiles of serum metabolome and fecal short-chain fatty acids (SCFAs), we investigated the changes of gut microbiome, serum metabolite features and fecal SCFAs from late pregnancy (LP) to postpartum (PO) stage. We found the significant changes of gut microbiota from LP to PO stage in both 16S rRNA gene sequencing and metagenomic sequencing analyses. The bacterial species from Lactobacillus, Streptococcus, and Clostridium were enriched at the LP stage, while the species from Bacteroides, Escherichia, and Campylobacter had higher abundances at the PO stage. Functional capacities of the gut microbiome were also significantly changed and associated with the shifts of gut bacteria. Untargeted metabolomic analyses revealed that the metabolite features related to taurine and hypotaurine metabolism, and arginine biosynthesis and metabolism were enriched at the LP stage, and positively associated with those bacterial species enriched at the LP stage, while the metabolite features associated with vitamin B6 and glycerophospholipid metabolism had higher abundances at the PO stage and were positively correlated with the bacteria enriched at the PO stage. Six kinds of SCFAs were measured in feces samples and showed higher concentrations at the LP stage. These results suggested that the changes of gut microbiome from LP to PO stage lead to the shifts of host lipid, amino acids and vitamin metabolism and SCFA production. The results from this study provided new insights for the changes of sow gut microbiome and host metabolism around parturition, and gave new knowledge for guiding the feeding and maternal care of sows from late pregnancy to lactation in the pig industry.
Characterization of METTL7B to Evaluate TME and Predict Prognosis by Integrative Analysis of Multi-Omics Data in Glioma
Authors: Chen Xiaochuan , Li Chao , Li Ying , Wu Shihong , Liu Wei , Lin Ting , Li Miaomiao , Weng Youliang , Lin Wanzun , Qiu Sufang
Published: September 2021

Glioma is the most common and aggressive type of primary brain malignant tumor with limited treatment approaches. Methyltransferase-like 7B (METTL7B) is associated with the pathogenesis of several diseases but is rarely studied in glioma. In this study, 1,493 glioma samples (data from our cohort, TCGA, and CGGA) expressing METTL7B were used to explore its prognostic value and mechanism in the immune microenvironment. Results showed that high expression of METTL7B is associated with poor prognosis and abundant immunosuppressive cells. Further, functional enrichment showed that METTL7B is involved in the negative regulation of immunity and carcinogenic signaling pathways. Moreover, a METTL7B-related prognostic signature constructed based on multi-omics showed a good prediction of the overall survival (OS) time of glioma patients. In conclusion, METTL7B is a potential prognostic biomarker. In addition, the prognostic prediction model constructed in this study can be used in clinical setups for the development of novel effective therapeutic strategies for glioma patients and improving overall survival.
Functional Metabolic Mapping Reveals Highly Active Branched-Chain Amino Acid Metabolism in Human Astrocytes, Which Is Impaired in iPSC-Derived Astrocytes in Alzheimer's Disease
Authors: Salcedo Claudia , Andersen Jens V. , Vinten Kasper Tore , Pinborg Lars H. , Waagepetersen Helle S. , Freude Kristine K. , Aldana Blanca I.
Published: September 2021

The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are important nitrogen donors for synthesis of glutamate, the main excitatory neurotransmitter in the brain. The glutamate carbon skeleton originates from the tricarboxylic acid (TCA) cycle intermediate α-ketoglutarate, while the amino group is derived from nitrogen donors such as the BCAAs. Disturbances in neurotransmitter homeostasis, mainly of glutamate, are strongly implicated in the pathophysiology of Alzheimer's disease (AD). The divergent BCAA metabolism in different cell types of the human brain is poorly understood, and so is the involvement of astrocytic and neuronal BCAA metabolism in AD. The goal of this study is to provide the first functional characterization of BCAA metabolism in human brain tissue and to investigate BCAA metabolism in AD pathophysiology using astrocytes and neurons derived from human-induced pluripotent stem cells (hiPSCs). Mapping of BCAA metabolism was performed using mass spectrometry and enriched [15N] and [13C] isotopes of leucine, isoleucine, and valine in acutely isolated slices of surgically resected cerebral cortical tissue from human brain and in hiPSC-derived brain cells carrying mutations in either amyloid precursor protein (APP) or presenilin-1 (PSEN-1). We revealed that both human astrocytes of acutely isolated cerebral cortical slices and hiPSC-derived astrocytes were capable of oxidatively metabolizing the carbon skeleton of BCAAs, particularly to support glutamine synthesis. Interestingly, hiPSC-derived astrocytes with APP and PSEN-1 mutations exhibited decreased amino acid synthesis of glutamate, glutamine, and aspartate derived from leucine metabolism. These results clearly demonstrate that there is an active BCAA metabolism in human astrocytes, and that leucine metabolism is selectively impaired in astrocytes derived from the hiPSC models of AD. This impairment in astrocytic BCAA metabolism may contribute to neurotransmitter and energetic imbalances in the AD brain.
Acid-Sensing Ion Channels: Expression and Function in Resident and Infiltrating Immune Cells in the Central Nervous System
Authors: Foster Victoria S. , Rash Lachlan D. , King Glenn F. , Rank Michelle M.
Published: September 2021

Peripheral and central immune cells are critical for fighting disease, but they can also play a pivotal role in the onset and/or progression of a variety of neurological conditions that affect the central nervous system (CNS). Tissue acidosis is often present in CNS pathologies such as multiple sclerosis, epileptic seizures, and depression, and local pH is also reduced during periods of ischemia following stroke, traumatic brain injury, and spinal cord injury. These pathological increases in extracellular acidity can activate a class of proton-gated channels known as acid-sensing ion channels (ASICs). ASICs have been primarily studied due to their ubiquitous expression throughout the nervous system, but it is less well recognized that they are also found in various types of immune cells. In this review, we explore what is currently known about the expression of ASICs in both peripheral and CNS-resident immune cells, and how channel activation during pathological tissue acidosis may lead to altered immune cell function that in turn modulates inflammatory pathology in the CNS. We identify gaps in the literature where ASICs and immune cell function has not been characterized, such as neurotrauma. Knowledge of the contribution of ASICs to immune cell function in neuropathology will be critical for determining whether the therapeutic benefits of ASIC inhibition might be due in part to an effect on immune cells.
Delayed Onset of Inhibition of Return in Visual Snow Syndrome
Authors: Foletta Paige J. , Clough Meaghan , McKendrick Allison M. , Solly Emma J. , White Owen B. , Fielding Joanne
Published: September 2021

Visual snow syndrome (VSS) is a complex, sensory processing disorder. We have previously shown that visual processing changes manifest in significantly faster eye movements toward a suddenly appearing visual stimulus and difficulty inhibiting an eye movement toward a non-target visual stimulus. We propose that these changes reflect poor attentional control and occur whether attention is directed exogenously by a suddenly appearing event, or endogenously as a function of manipulating expectation surrounding an upcoming event. Irrespective of how attention is captured, competing facilitatory and inhibitory processes prioritise sensory information that is important to us, filtering out that which is irrelevant. A well-known feature of this conflict is the alteration to behaviour that accompanies variation in the temporal relationship between competing sensory events that manipulate facilitatory and inhibitory processes. A classic example of this is the “Inhibition of Return” (IOR) phenomenon that describes the relative slowing of a response to a validly cued location compared to invalidly cued location with longer cue/target intervals. This study explored temporal changes in the allocation of attention using an ocular motor version of Posner's IOR paradigm, manipulating attention exogenously by varying the temporal relationship between a non-predictive visual cue and target stimulus. Forty participants with VSS (20 with migraine) and 20 controls participated. Saccades were generated to both validly cued and invalidly cued targets with 67, 150, 300, and 500 ms cue/target intervals. VSS participants demonstrated delayed onset of IOR. Unlike controls, who exhibited IOR with 300 and 500 ms cue/target intervals, VSS participants only exhibited IOR with 500 ms cue/target intervals. These findings provide further evidence that attention is impacted in VSS, manifesting in a distinct saccadic behavioural profile, and delayed onset of IOR. Whether IOR is perceived as the build-up of an inhibitory bias against returning attention to an already inspected location or a consequence of a stronger attentional orienting response elicited by the cue, our results are consistent with the proposal that in VSS, a shift of attention elicits a stronger increase in saccade-related activity than healthy controls. This work provides a more refined saccadic behavioural profile of VSS that can be interrogated further using sophisticated neuroimaging techniques and may, in combination with other saccadic markers, be used to monitor the efficacy of any future treatments.
Associations of Nutritional, Lifestyle, and Metabolic Factors With Non-alcoholic Fatty Liver Disease: An Umbrella Review With More Than 380,000 Participants
Authors: Xia Yang , Wu Qijun , Dai Huixu , Lv Jiale , Liu Yashu , Sun Hui , Jiang Yuting , Chang Qing , Niu Kaijun , Zhao Yuhong
Published: September 2021

Background & Aims:Nonalcoholic fatty liver disease (NAFLD) is the most common liver injury. We performed this umbrella review of meta-analyses to summarize the evidence on the associations of nutritional, lifestyle, and metabolic factors with NAFLD.

Methods:We searched the PubMed, Embase, and Web of Science databases from inception until July 2, 2020, to identify meta-analyses of observational studies which explored the associations of nutritional, lifestyle, and metabolic factors with NAFLD. Evidence levels were assessed using summary effect sizes, 95% prediction intervals, between-study heterogeneity, evidence of small-study effects, and evidence of excess significance bias for each meta-analysis. (No. of PROSPERO, CRD42020200124).

Results:Twenty two risk or protective factors from 10 published meta-analyses were included and studied. Three risk factors (sugar-sweetened beverage consumption, serum fetuin-A, and waist circumference) with highly suggestive levels of evidence and three risk factors (soft drink consumption, former smoking, and body mass index) with suggestive levels of evidence were identified. Only two protective factors (physical activity and serum vitamin D level [among adults in Western countries]) with suggestive levels of evidence were identified. Furthermore, other six risk factors and two protective factors with weak levels of evidence were identified.

Conclusions:We found varying levels of evidence of associations of nutritional, lifestyle, and metabolic factors and NAFLD. The results suggest that nutritional and lifestyle management should be considered as a major primary preventive strategy for NAFLD. Moreover, considering the low quality of included meta-analyses and limited area of research topics, future high-quality original studies and meta-analyses should be performed to study these associations.
Lymph Node Parameters Predict Adjuvant Chemoradiotherapy Efficacy and Disease-Free Survival in Pathologic N2 Non-Small Cell Lung Cancer
Authors: Zhang Chen-Chen , Hou Run-Ping , Feng Wen , Fu Xiao–Long
Published: September 2021

Pathologic N2 non-small cell lung cancer (NSCLC) is prominently intrinsically heterogeneous. We aimed to identify homogeneous prognostic subgroups and evaluate the role of different adjuvant treatments. We retrospectively collected patients with resected pathologic T1-3N2M0 NSCLC from the Shanghai Chest Hospital as the primary cohort and randomly allocated them (3:1) to the training set and the validation set 1. We had patients from the Fudan University Shanghai Cancer Center as an external validation cohort (validation set 2) with the same inclusion and exclusion criteria. Variables significantly related to disease-free survival (DFS) were used to build an adaptive Elastic-Net Cox regression model. Nomogram was used to visualize the model. The discriminative and calibration abilities of the model were assessed by time-dependent area under the receiver operating characteristic curves (AUCs) and calibration curves. The primary cohort consisted of 1,312 patients. Tumor size, histology, grade, skip N2, involved N2 stations, lymph node ratio (LNR), and adjuvant treatment pattern were identified as significant variables associated with DFS and integrated into the adaptive Elastic-Net Cox regression model. A nomogram was developed to predict DFS. The model showed good discrimination (the median AUC in the validation set 1: 0.66, range 0.62 to 0.71; validation set 2: 0.66, range 0.61 to 0.73). We developed and validated a nomogram that contains multiple variables describing lymph node status (skip N2, involved N2 stations, and LNR) to predict the DFS of patients with resected pathologic N2 NSCLC. Through this model, we could identify a subtype of NSCLC with a more malignant clinical biological behavior and found that this subtype remained at high risk of disease recurrence after adjuvant chemoradiotherapy.