bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comprehensive Game Theoretical Defense Strategy in Demand Side Management Against Price Tampering Attacks
Authors: Fu Rong , Chen Jie , Zhang Xiaofei , Zhang Jie
Published: November 2021

Price tamping attacks may cause market turbulence, attack detection and defense strategy are needed to study. Firstly, demand response characteristics are analyzed in a User Energy System. A quantitative model is established to describe the load changes caused by price tampering attacks. Secondly, a space-based cumulative intrusion detection method is proposed to pick up the discrepancy under tampering attacks. To verify the practicability of the proposed method, intrusion detection experiments are tested in the Principal Information and Safety Laboratory. Then, comprehensively considering the purchase of electricity from the power grid, self-generation, and load shedding, a quantitative model of attack consequences is established based on the allocation coefficient. Thus, the intrusion detection algorithm is used as a defense resource, and a demand-side defense protection strategy is formed to find an optimal deployment method based on non-cooperative game theory. The defensive protection strategy takes the quantitative model of attack consequences as the solution target, and solves the Nash equilibrium solution under different attack modes. Finally, in the IEEE-33 node system simulations, the defense resource is deployed using intrusion detection strategy, and the defense decision is executed to show the effectiveness of the comprehensive protection strategies.
Hosting Capacity Assessment in Distribution Networks Considering Wind–Photovoltaic–Load Temporal Characteristics
Authors: Du Nianchun , Tang Fei , Liao Qingfen , Wang Chenxu , Gao Xin , Xie Jiarui , Zhang Jian , Lu Runzhao
Published: November 2021

Under the background of clean and low-carbon energy transformation, renewable distributed generation is connected to the distribution system on a large scale. This study proposes a probabilistic assessment method of hosting capacity considering wind–photovoltaic–load temporal characteristics in distribution networks. First, based on time series of wind, photovoltaic, and load demands, a discretization–aggregation technique is introduced to generate and filter extreme combinations. The method can effectively reduce the scenarios that need to be evaluated. Then a holomorphic embedding method considering generation and load scaling directions is proposed. The holomorphic function of voltage about an embedding variable is established, and it is analytically expanded in the form of series. The hosting capacity restrained by the voltage violation problem is calculated quickly and accurately. Finally, the proposed stochastic framework is implemented to evaluate hosting capacity involving renewable energy types, penetration levels, and locations. The hosting capacity of single energy and hybrid wind–solar renewable energy systems is evaluated from the perspective of probability analysis. The results verify the outstanding performance of the hybrid wind–solar energy system in improving the hosting capacity.
Evolved Gas Analysis and Kinetics of Catalytic and Non-Catalytic Pyrolysis of Microalgae Chlorella sp. Biomass With Ni/θ-Al2O3 Catalyst via Thermogravimetric Analysis
Authors: Farooq Wasif , Ali Imtiaz , Raza Naqvi Salman , Sajid Mohd , Abbas Khan Hassnain , Adamu Sagir
Published: November 2021

This study investigates the efficacy of a prepared Ni/θ-Al2O3 catalyst during the pyrolytic conversion of Parachlorella kessleri HY-6 and compares the results with non-catalytic conversion. The catalyst was characterized by techniques such as Brunauer–Emmett–Teller (BET) for surface area, acidity, and X-ray powder diffraction (XRD). Isoconversional and combined kinetic methods were used to study the pyrolytic kinetics of the process. Ni/θ-Al2O3 was used at 10, 20, and 30% of the algal biomass. The addition of Ni/θ-Al2O3 facilitated the conversion by lowering the mean activation energy during pyrolysis. The catalytic effect was more pronounced at lower and higher conversions. The presence of the catalyst facilitated the pyrolysis as indicated by the lower value of activation energy and ∆H, and ∆G. Gases evolved during pyrolysis were qualitatively analyzed by FTIR to see the effect of catalyst on evolved gas composition during the pyrolysis process.
Review on the Change Law of the Properties and Performance of Polymer-Matrix Nuclear Radiation Shielding Materials Under the Coupling of Nuclear Radiation and Thermal Effects
Authors: Hu Guang , Sun Weiqiang , Yan Yihong , Wu Rongjun , Xu Hu
Published: November 2021

The polymer-matrix nuclear radiation shielding material is an important component of nuclear power plants. However, its mechanical properties and shielding performance gradually deteriorate due to the long-term synergy of nuclear radiation and thermal effects, which brings hidden dangers to the safe operation of the device. Based on this problem, this article makes a comprehensive review. First, the degradation of mechanical properties and shielding performance of polymer-matrix nuclear radiation materials in service is briefly described. Then, the research methods adopted by scholars to study the change law of properties and performance are introduced, and the main existing difficulties encountered by the study are summarized. Finally, the physical mechanism of the change of material properties is explained in detail, and a reference approach to solving the problem is proposed.
Bacterial Diversity in House Dust: Characterization of a Core Indoor Microbiome
Authors: Thompson Jonathan R. , Argyraki Ariadne , Bashton Matthew , Bramwell Lindsay , Crown Matthew , Hursthouse Andrew S. , Jabeen Khadija , Marinho Reis Paula , Namdeo Anil , Nelson Andrew , Pearce David A. , Potgieter-Vermaak Sanja , Rasmussen Pat E. , Wragg Joanna , Entwistle Jane A.
Published: November 2021

Our indoor microbiome consists of a wide range of microbial taxa. Whilst many of these microbes are benign, some are beneficial, some harmful, yet our knowledge of the spatial heterogeneity of bacterial assemblages in our residential environment remains limited. To investigate the existence of a common core house dust bacterial microbiome we selected household vacuum dusts, collected through a citizen science approach, from homes across two bioclimatic regions (UK, Oceanic/Maritime and Greece, Mediterranean). Following the extraction of DNA from each dust sample, we targeted the bacterial 16S rRNA gene using Illumina NextSeq sequencing. PERMANOVA analysis of the microbial communities at family level grouped samples within their distinct bioclimatic region and SIMPER analysis at genus level identified the statistically significant taxa responsible for driving diversity between these groups. A “common to all” core house dust microbiome consisted of Acinetobacter, Massalia, Rubellimicrobium, Sphingomonas and Staphylococcus; genera typically associated with human occupancy and common environmental sources. Additionally, a “unique location specific” microbiome was identified, reflective of the bioclimatic region. The Greek dusts indicated a lower average diversity than the UK house dusts, with a high abundance of Rhizobiaceae in the Greek samples. Our study highlights citizen science as a powerful approach to access the indoor residential environment, at scale, and establishes the existence of a “core” house dust microbiome independent of bioclimatic region.
Occurrence, Profile, and Potential Risks of Novel and Legacy Polyfluoroalkyl Substances in Bullfrogs: Pilot Study in an Intensive Aquaculture Region, China
Authors: Sun Qiongping , Xiong Yonglong , Bi Ran , Zhan Xinyi , Fan Yueyao , Su Chuanghong , Chen Zhenwei , Zheng Zhao , Diao Jieyi , Wang Tieyu
Published: November 2021

Per- and polyfluoroalkyl substances (PFASs) have captured worldwide attention due to their persistent and bioaccumulative characteristics. The bullfrog is a highly nutritious and edible aquatic product, but the PFAS accumulation characteristics of bullfrogs had not been paid attention. The present study analyzed the PFAS concentrations in different tissues of cultured bullfrogs and relevant water and sediments collected from the aquaculture region in the coastal area of South China. Results showed that total PFAS concentrations were 50.26–364.25 ng/L in water, with a mean of 135.58 ng/L; concentrations in effluent water were significantly higher than those in influent water, which means bullfrog farming could increase contaminants into the surroundings. The total PFAS concentrations varied from 2.89 to 162.26 ng/g·dw in sediment. The distribution profile of PFASs in sediment was similar to that of water, with short chain playing a significant role. Total PFASs in bullfrog tissues were 3.36–84.07 ng/g·dw, with the highest values in the digestive system (intestines and stomach). As for one novel PFAS alternative, chlorinated polyfluorinated ether sulfonate (F-53B) was found at high detectable levels in all habitat samples and had a higher value of logarithmic bioaccumulation factors. The estimated dietary intake (EDI) for residents in the study area was generally higher than that in other regions; however, the hazard ratios (HRs) for most detected PFASs were far below the safety threshold value “1.” These results suggest that frequent consumption of these bullfrogs would basically not cause severe health effects on local residents in terms of PFASs.
Microplastics Reduce the Negative Effects of Litter-Derived Plant Secondary Metabolites on Nematodes in Soil
Authors: Kim Shin Woong , Liang Yun , Lozano Yudi M. , Rillig Matthias C.
Published: November 2021

Microplastics and plant litter are ubiquitous in the soil environment, and both materials can influence soil properties and biota. Plant litter releases secondary metabolites (e.g., phenolic compounds) during the decomposition process, including chemical compounds active in plant defense. Effects of microplastics and plant litter on soil biota have been studied independently but we have limited information about the combined effects of both sources of chemicals. Here, we specifically focused on the interaction between plant litter and microplastics, as well as their potential effects on soil biota (i.e., nematodes). We used soils from a previous experiment that included three different types of microplastic fibers (MFs) and four different types of plant litter, which were incubated in the soil in all combinations of materials. After soil incubation (42 days) in the previous experiment, we here tested for effects on nematodes (Caenorhabditis elegans). Plant litter treatments negatively affected the reproduction of nematodes, but these effects were reduced when the soils were incubated along with MFs. We measured the phenolic concentrations in plant litter extracts in a kinetic experiment and found that phenolic concentrations significantly decreased with some of the MF additions. Our results suggest that microplastics can affect the potential effects of natural chemicals such as plant phenolic compounds. We urge future studies to consider this possibility as a key explanatory process underpinning effects of microplastic in the soil environment.
A Comparative Analysis of Super-Enhancers and Broad H3K4me3 Domains in Pig, Human, and Mouse Tissues
Authors: Peng Yanling , Kang Huifang , Luo Jing , Zhang Yubo
Published: November 2021

Super-enhancers (SEs) and broad H3K4me3 domains (BDs) are crucial regulators in the control of tissue identity in human and mouse. However, their features in pig remain largely unknown. In this study, by integrative computational analyses of epigenomic and transcriptomic data, we have characterized SEs and BDs in six pig tissues and analyzed their conservation in comparison with human and mouse tissues. Similar to human and mouse, pig SEs and BDs display higher tissue specificity than their typical counterparts. Genes proximal to SEs and BDs are associated with tissue identity in most tissues. About 55–182 SEs (5–17% in total) and 99–309 BDs (8–16% in total) across pig tissues are considered as functionally conserved elements because they have orthologous SEs and BDs in human and mouse. However, these elements do not necessarily exhibit sequence conservation. The functionally conserved SEs are correlated to tissue identity in majority of pig tissues, while those conserved BDs are linked to tissue identity in a few tissues. Our study provides resources for future gene regulatory studies in pig. It highlights that SEs are more effective in defining tissue identity than BDs, which is contrasting to a previous study. It also provides novel insights on understanding the sequence features of functionally conserved elements.
Structural Equation Modeling of In silico Perturbations
Authors: Li Jianying , Bushel Pierre R. , Lin Lin , Day Kevin , Wang Tianyuan , DeMayo Francesco J. , Wu San-Pin , Li Jian-Liang
Published: November 2021

Gene expression is controlled by multiple regulators and their interactions. Data from genome-wide gene expression assays can be used to estimate molecular activities of regulators within a model organism and extrapolate them to biological processes in humans. This approach is valuable in studies to better understand complex human biological systems which may be involved in diseases and hence, have potential clinical relevance. In order to achieve this, it is necessary to infer gene interactions that are not directly observed (i.e. latent or hidden) by way of structural equation modeling (SEM) on the expression levels or activities of the downstream targets of regulator genes. Here we developed an R Shiny application, termed “Structural Equation Modeling of In silico Perturbations (SEMIPs)” to compute a two-sided t-statistic (T-score) from analysis of gene expression data, as a surrogate to gene activity in a given human specimen. SEMIPs can be used in either correlational studies between outcome variables of interest or subsequent model fitting on multiple variables. This application implements a 3-node SEM model that consists of two upstream regulators as input variables and one downstream reporter as an outcome variable to examine the significance of interactions among these variables. SEMIPs enables scientists to investigate gene interactions among three variables through computational and mathematical modeling (i.e. in silico). In a case study using SEMIPs, we have shown that putative direct downstream genes of the GATA Binding Protein 2 (GATA2) transcription factor are sufficient to infer its activities in silico for the conserved progesterone receptor (PGR)-GATA2-SRY-box transcription factor 17 (SOX17) genetic network in the human uterine endometrium.
Effects of Maternal Nutrition on Female Offspring Weight Gain and Sexual Development
Authors: Cracco Roberta Cavalcante , Bussiman Fernando de Oliveira , Polizel Guilherme Henrique Gebim , Furlan Édison , Garcia Nara Pontes , Poit Diego Angelo Schmidt , Pugliesi Guilherme , Santana Miguel Henrique de Almeida
Published: November 2021

Maternal nutrition during pregnancy influences postnatal life of animals; nevertheless, few studies have investigated its effects on the productive performance and reproductive development of heifers. This study evaluated the performance, reproductive development, and correlation between reproduction × fat thickness and performance × ribeye area (REA) traits of heifers. We also performed an exploratory genomic association during the rearing period in heifers submitted to fetal programming. The study comprised 55 Nellore heifers born to dams exposed to one of the following nutritional planes: control, without protein-energy supplementation; PELT, protein-energy last trimester, protein-energy supplementation offered in the final third of pregnancy; and PEWG, protein-energy whole gestation, protein-energy supplementation upon pregnancy confirmation. Protein-energy supplementation occurred at the level of 0.3% live weight. After weaning, heifers were submitted to periodic evaluations of weight and body composition by ultrasonography. From 12 to 18 months, we evaluated the reproductive tract of heifers to monitor its development for sexual precocity and ovarian follicle population. The treatments had no effect (p > 0.05) on average daily gain; however, the weight of the animals showed a significant difference over time (p = 0.017). No differences were found between treatments for REA, backfat, and rump fat thickness, nor for puberty age, antral follicular count, and other traits related to reproductive tract development (p > 0.05). The correlation analysis between performance traits and REA showed high correlations (r > 0.37) between REA at weaning and year versus weight from weaning until yearling; however, no correlation was found for reproductive development traits versus fat thickness (p > 0.05). The exploratory genomic association study showed one single-nucleotide polymorphism (SNP) for each treatment on an intergenic region for control and PEWG, and the one for PELT on an intronic region of RAPGEF1 gene. Maternal nutrition affected only the weight of the animals throughout the rearing period.
Ancient Mitogenomes Reveal the Domestication and Distribution of Cattle During the Longshan Culture Period in North China
Authors: Zhang Xing , Yang Liu , Hou Lingyun , Li Hua , Xiang Hai , Zhao Xingbo
Published: November 2021

Cattle, as an important tool for agricultural production in ancient China, have a complex history of domestication and distribution in China. Although it is generally accepted that ancient Chinese taurine cattle originated from the Near East, the explanation regarding their spread through China and whether or not this spread was associated with native aurochs during ancient times are still unclear. In this study, we obtained three nearly complete mitochondrial genomes (mitogenomes) from bovine remains dating back ca. 4,000 years at the Taosi and Guchengzhai sites in North China. For the first time at the mitogenome level, phylogenetic analyses confirmed the approximately 4,000-year-old bovines from North China as taurine cattle. All ancient cattle from both sites belonged to the T3 haplogroup, suggesting their origin from the Near East. The high affinity between ancient samples and southern Chinese taurine cattle indicated that ancient Chinese cattle had a genetic contribution to the taurine cattle of South China. A rapid decrease in the female effective population size ca. 4.65 thousand years ago (kya) and a steep increase ca. 1.99 kya occurred in Chinese taurine cattle. Overall, these results provide increasing evidence of the origin of cattle in the middle Yellow River region of China.
Leukocyte Membrane Enzymes Play the Cell Adhesion Game
Authors: López-Cortés Georgina I. , Díaz-Alvarez Laura , Ortega Enrique
Published: November 2021

For a long time, proteins with enzymatic activity have not been usually considered to carry out other functions different from catalyzing chemical reactions within or outside the cell. Nevertheless, in the last few years several reports have uncovered the participation of numerous enzymes in other processes, placing them in the category of moonlighting proteins. Some moonlighting enzymes have been shown to participate in complex processes such as cell adhesion. Cell adhesion plays a physiological role in multiple processes: it enables cells to establish close contact with one another, allowing communication; it is a key step during cell migration; it is also involved in tightly binding neighboring cells in tissues, etc. Importantly, cell adhesion is also of great importance in pathophysiological scenarios like migration and metastasis establishment of cancer cells. Cell adhesion is strictly regulated through numerous switches: proteins, glycoproteins and other components of the cell membrane. Recently, several cell membrane enzymes have been reported to participate in distinct steps of the cell adhesion process. Here, we review a variety of examples of membrane bound enzymes participating in adhesion of immune cells.
Dietary β-Carotene on Postpartum Uterine Recovery in Mice: Crosstalk Between Gut Microbiota and Inflammation
Authors: Yang Xizi , He Ziyu , Hu Ruizhi , Yan Jiahao , Zhang Qianjin , Li Baizhen , Yuan Xupeng , Zhang Hongfu , He Jianhua , Wu Shusong
Published: November 2021

As the precursor of vitamin A, β-carotene has a positive effect on reproductive performance. Our previous study has shown that β-carotene can increase antioxidant enzyme activity potentially through regulating gut microbiota in pregnant sows. This study aimed to clarify the effect of β-carotene on reproductive performance and postpartum uterine recovery from the aspect of inflammation and gut microbiota by using a mouse model. Twenty-seven 6 weeks old female Kunming mice were randomly assigned into 3 groups (n=9), and fed with a diet containing 0, 30 or 90 mg/kg β-carotene, respectively. The results showed that dietary supplementation of β-carotene reduced postpartum uterine hyperemia and uterine mass index (P<0.05), improved intestinal villus height and villus height to crypt depth ratio, decreased serum TNF-α and IL-4 concentration (P<0.05), while no differences were observed in litter size and litter weight among three treatments. Characterization of gut microbiota revealed that β-carotene up-regulated the relative abundance of genera Akkermansia, Candidatus Stoquefichus and Faecalibaculum, but down-regulated the relative abundance of Alloprevotella and Helicobacter. Correlation analysis revealed that Akkermansia was negatively correlated with the IL-4 concentration, while Candidatus Stoquefichus and Faecalibaculum had a negative linear correlation with both TNF-α and IL-4 concentration. On the other hand, Alloprevotella was positively correlated with the TNF-α, and Helicobacter had a positive correlation with both TNF-α and IL-4 concentration. These data demonstrated that dietary supplementation of β-carotene contributes to postpartum uterine recovery by decreasing postpartum uterine hemorrhage and inhibiting the production of inflammatory cytokines potentially through modulating gut microbiota.
Identification of Immune-Related Gene Signatures in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
Authors: Li Na , Wang Jiahong , Zhan Xianquan
Published: November 2021

Accumulating evidence indicates that immunotherapy helped to improve the survival and quality-of-life of patients with lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC) besides chemotherapy and gene targeting treatment. This study aimed to develop immune-related gene signatures in LUAD and LUSC subtypes, respectively. LUAD and LUSC samples were divided into high- and low-abundance groups of immune cell infiltration (Immunity_H and Immunity_L) based on the abundance of immune cell infiltrations. The distribution of immune cells was significantly different between the high- and low-immunity subtypes in LUAD and LUSC samples. The differentially expressed genes (DEGs) between those two groups in LUAD and LUSC contain some key immune-related genes, such as PDL1, PD1, CTLA-4, and HLA families. The DEGs were enriched in multiple immune-related pathways. Furthermore, the seven-immune-related-gene-signature (CD1B, CHRNA6, CLEC12B, CLEC17A, CLNK, INHA, and SLC14A2) prognostic model-based high- and low-risk groups were significantly associated with LUAD overall survival and clinical characteristics. The eight-immune-related-gene-signature (C4BPB, FCAMR, GRAPL, MAP1LC3C, MGC2889, TRIM55, UGT1A1, and VIPR2) prognostic model-based high- and low-risk groups were significantly associated with LUSC overall survival and clinical characteristics. The prognostic models were tested as good ones by receiver operating characteristic, principal component analysis, univariate and multivariate analysis, and nomogram. The verifications of these two immune-related-gene-signature prognostic models showed consistency in the train and test cohorts of LUAD and LUSC. In addition, patients with LUAD in the low-risk group responded better to immunotherapy than those in the high-risk group. This study revealed two reliable immune-related-gene-signature models that were significantly associated with prognosis and tumor microenvironment cell infiltration in LUAD and LUSC, respectively. Evaluation of the integrated characterization of multiple immune-related genes and pathways could help to predict the response to immunotherapy and monitor immunotherapy strategies.
Enhanced Immunogenicity of a Whole-Inactivated Influenza A Virus Vaccine Using Optimised Irradiation Conditions
Authors: Singleton Eve Victoria , Gates Chloe Jayne , David Shannon Christa , Hirst Timothy Raymond , Davies Justin Bryan , Alsharifi Mohammed
Published: November 2021

Influenza A virus presents a constant pandemic threat due to the mutagenic nature of the virus and the inadequacy of current vaccines to protect against emerging strains. We have developed a whole-inactivated influenza vaccine using γ-irradiation (γ-Flu) that can protect against both vaccine-included strains as well as emerging pandemic strains. γ-irradiation is a widely used inactivation method and several γ-irradiated vaccines are currently in clinical or pre-clinical testing. To enhance vaccine efficacy, irradiation conditions should be carefully considered, particularly irradiation temperature. Specifically, while more damage to virus structure is expected when using higher irradiation temperatures, reduced radiation doses will be required to achieve sterility. In this study, we compared immunogenicity of γ-Flu irradiated at room temperature, chilled on ice or frozen on dry ice using different doses of γ-irradiation to meet internationally accepted sterility assurance levels. We found that, when irradiating at sterilising doses, the structural integrity and vaccine efficacy were well maintained in all preparations regardless of irradiation temperature. In fact, using a higher temperature and lower radiation dose appeared to induce higher neutralising antibody responses and more effective cytotoxic T cell responses. This outcome is expected to simplify irradiation protocols for manufacturing of highly effective irradiated vaccines.
Addition of Fibroblast-Stromal Cell Markers to Immune Synovium Pathotypes Better Predicts Radiographic Progression at 1 Year in Active Rheumatoid Arthritis
Authors: Zhang Xue-Pei , Ma Jian-Da , Mo Ying-Qian , Jing Jun , Zheng Dong-Hui , Chen Le-Feng , Wu Tao , Chen Chu-Tao , Zhang Qian , Zou Yao-Yao , Lin Jian-Zi , Xu Yan-Hui , Zou Yao-Wei , Yang Ze-Hong , Ling Li , Miossec Pierre , Dai Lie
Published: November 2021

Objectives

This study aims to investigate if addition of fibroblast-stromal cell markers to a classification of synovial pathotypes improves their predictive value on clinical outcomes in rheumatoid arthritis (RA).

Methods

Active RA patients with a knee needle synovial biopsy at baseline and finished 1-year follow-up were recruited from a real-world prospective cohort. Positive staining for CD20, CD38, CD3, CD68, CD31, and CD90 were scored semiquantitatively (0-4). The primary outcome was radiographic progression defined as a minimum increase of 0.5 units of the modified total Sharp score from baseline to 1 year.

Results

Among 150 recruited RA patients, 123 (82%) had qualified synovial tissue. Higher scores of CD20+ B cells, sublining CD68+ macrophages, CD31+ endothelial cells, and CD90+ fibroblasts were associated with less decrease in disease activity and greater increase in radiographic progression. A new fibroblast-based classification of synovial pathotypes giving more priority to myeloid and stromal cells classified samples as myeloid-stromal (57.7%, 71/123), lymphoid (31.7%, 39/123), and paucicellular pathotypes (10.6%, 13/123). RA patients with myeloid-stromal pathotype showed the highest rate of radiographic progression (43.7% vs. 23.1% vs. 7.7%, p = 0.011), together with the lowest rate of Boolean remission at 3, 6, and 12 months. Baseline synovial myeloid-stromal pathotype independently predicted radiographic progression at 1 year (adjusted OR: 3.199, 95% confidence interval (95% CI): 1.278, 8.010). Similar results were obtained in a subgroup analysis of treatment-naive RA.

Conclusions

This novel fibroblast-based myeloid-stromal pathotype could predict radiographic progression at 1 year in active RA patients which may contribute to the shift of therapeutic decision in RA.
Glycolysis Rate-Limiting Enzymes: Novel Potential Regulators of Rheumatoid Arthritis Pathogenesis
Authors: Zuo Jianlin , Tang Jinshuo , Lu Meng , Zhou Zhongsheng , Li Yang , Tian Hao , Liu Enbo , Gao Baoying , Liu Te , Shao Pu
Published: November 2021

Rheumatoid arthritis (RA) is a classic autoimmune disease characterized by uncontrolled synovial proliferation, pannus formation, cartilage injury, and bone destruction. The specific pathogenesis of RA, a chronic inflammatory disease, remains unclear. However, both key glycolysis rate-limiting enzymes, hexokinase-II (HK-II), phosphofructokinase-1 (PFK-1), and pyruvate kinase M2 (PKM2), as well as indirect rate-limiting enzymes, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), are thought to participate in the pathogenesis of RA. In here, we review the latest literature on the pathogenesis of RA, introduce the pathophysiological characteristics of HK-II, PFK-1/PFKFB3, and PKM2 and their expression characteristics in this autoimmune disease, and systematically assess the association between the glycolytic rate-limiting enzymes and RA from a molecular level. Moreover, we highlight HK-II, PFK-1/PFKFB3, and PKM2 as potential targets for the clinical treatment of RA. There is great potential to develop new anti-rheumatic therapies through safe inhibition or overexpression of glycolysis rate-limiting enzymes.
Fpr2/CXCL1/2 Controls Rapid Neutrophil Infiltration to Inhibit Streptococcus agalactiae Infection
Authors: Sun Zeyu , Huang Wenhua , Zheng Yuling , Liu Peng , Yang Wenbo , Guo Zinan , Kong Decong , Lv Qingyu , Zhou Xinyu , Du Zongmin , Jiang Hua , Jiang Yongqiang
Published: November 2021

Streptococcus agalactiae, also known as group B streptococcus (GBS), can cause pneumonia, meningitis, and bacteremia, making it a pathogen that can increase the risk of death in newborns and immunodeficient individuals. Neutrophils are the first barrier to a host’s innate immune defense against these infections. Fpr2(Formyl peptide receptor 2) is an important chemotactic receptor of neutrophils, though its activation would cause pro- and anti-inflammatory effects. In this study, we found that mice without Fpr2 receptor were highly susceptible to GBS infections. These mice demonstrated decreased chemotaxis to neutrophils, decreased bactericidal ability of neutrophils, and high mortality. RNA-seq and Luminex assay indicated that Fpr2 activates key signal molecules downstream and produces chemokines CXCL1/2 to chemotaxis neutrophils. Like Fpr2-/-, CXCL1/2 or neutrophil depletion impairs host’s ability to defend against GBS infection. Altogether, these data indicate that Fpr2 contributes to a host’s ability to control GBS infection and that a lack of Fpr2 was associated with selective impairment during the production of chemokines CXCL1 and CXCL2 as well as neutrophil recruitment. Here, We clarified that Fpr2, as a chemotactic receptor, could not only directly chemotactic neutrophils, but also regulate the production of chemokines to control infection by chemotactic neutrophils.
Recent Advances in Developmental Hematopoiesis: Diving Deeper With New Technologies
Authors: Weijts Bart , Yvernogeau Laurent , Robin Catherine
Published: November 2021

The journey of a hematopoietic stem cell (HSC) involves the passage through successive anatomical sites where HSCs are in direct contact with their surrounding microenvironment, also known as niche. These spatial and temporal cellular interactions throughout development are required for the acquisition of stem cell properties, and for maintaining the HSC pool through balancing self-renewal, quiescence and lineage commitment. Understanding the context and consequences of these interactions will be imperative for our understanding of HSC biology and will lead to the improvement of in vitro production of HSCs for clinical purposes. The aorta-gonad-mesonephros (AGM) region is in this light of particular interest since this is the cradle of HSC emergence during the embryonic development of all vertebrate species. In this review, we will focus on the developmental origin of HSCs and will discuss the novel technological approaches and recent progress made to identify the cellular composition of the HSC supportive niche and the underlying molecular events occurring in the AGM region.
Data-Limited Stock Assessment for Fish Species Devoid of Catch Statistics: Case Studies for Pampus argenteus and Setipinna taty in the Bohai and Yellow Seas
Authors: Han Qingpeng , Shan Xiujuan , Jin Xianshi , Gorfine Harry , Yang Tao , Su Chengcheng
Published: November 2021

For many fish stocks, such as Pampus argenteus and Setipinna taty in China, size composition data are more accessible than catch data. Varied results can arise when different length-based stock assessment models are applied to these data, and fishery managers often need to reconcile conflicting estimates of population status. Superensemble modeling, a relatively recent innovation in fish stock assessments commonly used in other fields, may provide an effective solution to resolving uncertainties among the results from multiple length-based models. To verify potential for this approach to improve estimates of population status, we applied ensemble modeling to fit simulated data of P. argenteus and S. taty in the Bohai and Yellow Seas using predictions from a length-based integrated mixed effects (LIME) and length-based spawning potential ratio (LB-SPR) models as covariables in a superensemble model developed in this study. All simulation modeling of P. argenteus and S. taty in the Bohai and Yellow Seas was conducted using the operating model in the R package LIME. Initially, the LIME and LB-SPR performances were tested separately under three scenarios of fishing mortality and recruitment variability (“equilibrium scenario,” “endogenous scenario,” and “one-way base scenario”). Then, estimates of spawning potential ratio (SPR) were combined with the superensemble models (a linear model, a support vector machines, a random forest and a boosted regression tree). We trained our superensemble models with 80% of the simulated data and tested them with the remaining 20%. Our results showed that superensemble modeling substantially improved the estimates of SPR, with support vector machines performing the best at estimating population status: precision improved by 12.7% for S. taty and 8% for P. argenteus on average (namely, median absolute proportional error decreased by 0.127 and 0.08 on average) compared to the individual models. This finding has important implications for fisheries management in the context of species for which catch data are unavailable. Applying the size composition survey data, the results from support vector machines superensemble model suggested that neither S. taty nor P. argenteus in the Bohai Sea in 2019 are overfished, but the stock status of P. argenteus warrants vigilant monitoring.
Connectivity Patterns for Direct Developing Invertebrates in Fragmented Marine Habitats: Fish Farms Fouling as Source Population in the Establishment and Maintenance of Local Metapopulations
Authors: Fernandez-Gonzalez Victoria , Navarro-Mayoral Sandra , Sanchez-Jerez Pablo
Published: November 2021

Artificial structures can be considered as high spatially structured habitats in the marine pelagic system, where patch connectivity would be strongly dependent on the exchange of larvae or dispersing individuals. Fish-farms located offshore may alter ecological connectivity, modifying trophic resources, and species dispersal among patches. High population densities of invertebrates can be found associated with fish-farm fouling communities, which can act as a seed source, contributing to the patterns of connectivity through individuals exchange between subpopulations or with sink populations. A field experiment was performed to analyse the role of fish-farms in the colonisation of new uninhabited habitats (floating experimental units) located at different positions relative to the fish farm and the main current, containing artificial habitats with and without feed pellets similar to those used in the fish farm. Amphipods were used as example of direct developing invertebrates for studying dispersing individuals from the fish farm to the new habitats. The richest and most abundant populations in this study were found close to and downstream of the fish farm, surpassing 1,000 amphipods at their maximum. Moreover, some floating habitats located more than 2 km from the fish farm were colonised in only 15 days. Thus, the role of fish farms has been shown to extend beyond a ‘stepping-stones’ effect in species dispersal, and have an additional effect on ecological connectivity by increasing population sizes and acting as population source. Our study aims to provide recommendations for coastal zone management in order to predict potential spread from fish farms to other platforms in the future and promote solutions related to interactions and consequences of connectivity within and between marine facilities.
A Molecular Dynamics Simulation Study: The Inkjet Printing of Graphene Inks on Polyimide Substrates
Authors: Wu Lingjun , Wang Wei , Zhao Haitao , Gao Libo , Lu Jibao , Sun Rong
Published: November 2021

Inkjet printing-based 2D materials for flexible electronics have aroused much interest due to their highly low-cost customization and manufacturing resolution. However, there is a lack of investigation and essential understanding of the surface adhesion affected by the printing parameters at the atomic scale. Herein, we conducted a systematic molecular dynamics simulation investigating the inkjet printing of graphitic inks on polyimide substrates under various conditions. Simulations under different temperatures, inkjet velocities, and mechanical loadings such as pressure and deformation are performed. The results show that the best adhesion is achieved in the plasma-modified polyimide/graphene-oxide (mPI/GO) interfacial system (the interaction energy (Ein) between mPI and GO is ca. 1.2 times than with graphene). The adhesion strength decreases with increasing temperature, and higher inkjet velocities lead to both larger impact force as well as interfacial fluctuation, while the latter may result in greater interfacial instability. When loaded with pressure, the adhesion strength reaches a threshold without further improvement as continuing compacting of polymer slabs can hardly be achieved. The detachment of the interfaces was also explored and mPI/GO shows better resistance against delamination. Hopefully, our simulation study paves the way for future inkjet printing-based manufacturing of graphene-based flexible electronics.
The Influence of Sevelamer Hydrochloride and Calcium Carbonate on Markers of Inflammation and Oxidative Stress in Hemodialysis at Six Months of Follow-Up
Authors: Díaz-De la Cruz Elodia Nataly , Cerrillos-Gutiérrez José Ignacio , García-Sánchez Andrés , Prado-Nevárez Carlos Gerardo , Andrade-Sierra Jorge , Jalomo-Martínez Basilio , Banda-López Adriana , Rojas-Campos Enrique , Miranda-Díaz Alejandra Guillermina
Published: November 2021

Patients with end-stage renal disease (ESRD) present alterations in mineral and bone metabolism. Hyperphosphatemia in ESRD is considered an independent risk factor for cardiovascular disease (CVD), increasing morbidity, and mortality. Sevelamer hydrochloride is a calcium-free, non-absorbable phosphate-chelating polymer. Calcium carbonate chelator is helpful in controlling serum phosphate levels. There is insufficient information on the influence of sevelamer hydrochloride and calcium carbonate on the behavior of oxidative stress (OS) markers and inflammation in patients on hemodialysis (HD). A randomized open clinical trial was carried out on patients to evaluate sevelamer hydrochloride and calcium carbonate influence at 6 months of study follow-up. Levels of oxidants (LPO, NO, and 8-isoprostanes), antioxidants (SOD and TAC), oxidative DNA damage (8-OHdG and hOGG1), pro-inflammatory cytokines (IL-6 and TNF-α), and inflammation markers (ferritin and C-reactive protein) were measured with colorimetric and ELISA methods. We found a significant increase in oxidants LPO and NO, and antioxidants SOD and TAC, and downregulation of IL-6 and TNF-α. Ferritin decrease at 6 months follow-up in the sevelamer hydrochloride group. Increase in C-reactive protein was found in the group of patients treated with calcium carbonate. In conclusion, we found an oxidative state imbalance with increase in LPO and NO oxidants. The activity of the antioxidant enzymes (SOD and TAC) was also found to increase, suggesting a compensatory effect in the face of increase in oxidants. The same phenomenon was observed with increase in the oxidative damage marker to DNA and the increase in the DNA repair enzyme, suggesting a compensatory effect. Pro-inflammatory cytokines were predominantly downregulated by TNF-α in the group that ingested sevelamer hydrochloride in the final determination at 6 months of follow-up. Serum ferritin levels decreased significantly at the end of follow-up in patients on HD in the sevelamer hydrochloride group. The management of hyperphosphatemia with sevelamer hydrochloride appears to have obvious anti-inflammatory and antioxidant benefits.
Perspectives, Expectations, and Concerns of European Patient Advocates on Advanced Therapy Medicinal Products
Authors: Benvenuti Stefano , Wang Chiuhui Mary , Borroni Simona
Published: November 2021

This paper presents the results of a qualitative study based on semi-structured interviews of 10 expert patient advocates on several different issues around Advanced Therapy Medicinal Products (ATMPs). The interviews were conducted between February and May 2020 based on a guideline with a list of 8 topics that covered concerns about safety and ethics, access problems and limitations, pricing of ATMPs and educational needs for patient communities. Overall, the interviewees expressed a high degree of convergence of opinions on most of the topics and especially on the identification of the reasons for concern. Conversely, when asked about possible solutions, quite a wide range of solutions were proposed, although with many common points. However, it highlights that the debate is still in its infancy and that there are not yet consolidated positions across the whole community. A general concern emerging from all the interviews is the potential limitation of access to approved ATMPs, both due to the high prices and to the geographical concentration of treatment centers. However, patients recognize the value of a model with a limited number of specialized clinical centers administering these therapies. On the ethical side, patients do not show particular concern as long as ATMPs and the underlying technology is used to treat severe diseases. Finally, patients are asking for both more education on ATMPs as well as for a more continuous involvement of patient representatives in the whole “life-cycle” of a new ATMP, from the development phase to the authorization, from the definition of the reimbursement scheme to the collection of Real Word Data on safety and long-term efficacy of the treatment.
Metabolic Reprogramming and Reconstruction: Integration of Experimental and Computational Studies to Set the Path Forward in ADPKD
Authors: Pagliarini Roberto , Podrini Christine
Published: November 2021

Metabolic reprogramming is a key feature of Autosomal Dominant Polycystic Kidney Disease (ADPKD) characterized by changes in cellular pathways occurring in response to the pathological cell conditions. In ADPKD, a broad range of dysregulated pathways have been found. The studies supporting alterations in cell metabolism have shown that the metabolic preference for abnormal cystic growth is to utilize aerobic glycolysis, increasing glutamine uptake and reducing oxidative phosphorylation, consequently resulting in ADPKD cells shifting their energy to alternative energetic pathways. The mechanism behind the role of the polycystin proteins and how it leads to disease remains unclear, despite the identification of numerous signaling pathways. The integration of computational data analysis that accompanies experimental findings was pivotal in the identification of metabolic reprogramming in ADPKD. Here, we summarize the important results and argue that their exploitation may give further insights into the regulative mechanisms driving metabolic reprogramming in ADPKD. The aim of this review is to provide a comprehensive overview on metabolic focused studies and potential targets for treatment, and to propose that computational approaches could be instrumental in advancing this field of research.
Exploring Factors Associated With the Motivation of Clinical Pharmacists: A Focus on the South African Context
Authors: Crafford Lucille , Wouters Anouk , Bronkhorst Elmien , Gous Andries G. S. , Kusurkar Rashmi A.
Published: November 2021

Introduction: Pharmacy practice in many middle to low-income countries has slowly transitioned from being product-focused to a more patient-focused clinical practice. Lack of motivation is one of the factors contributing to the scarcity of pharmacists in the wards. As little is known about motivation in clinical pharmacists, this study aimed to obtain insight into the quantity and quality of their work motivation and factors associated with it.

Methods: Self-determination Theory, used as the framework, describes autonomous motivation as being generated from within or through personal endorsement and controlled motivation as originating from external factors. An online questionnaire including the Academic Motivation Scale to measure autonomous motivation, controlled motivation and amotivation, was sent to clinical pharmacy graduates from 2000 to 2020 across South Africa, followed by interviews to explain some results. Independent t-test was used to analyze differences in motivation of clinical pharmacists to perform clinical services based on personal and environmental factors. Interview data were transcribed and analyzed to explain significant quantitative findings.

Results: Higher amotivation was found in graduates who are currently not practicing in dedicated clinical pharmacist positions, as well as in graduates who do not receive additional financial benefits for clinical services. We found no significant differences in the work motivation of clinical pharmacists based on their gender, age, current practice setting, work experience and additional training received. The interviews revealed that relatedness and autonomy are the most important factors for clinical pharmacists' work motivation.

Discussion: Overall participants had a high mean autonomous motivation, a high mean controlled motivation and low mean amotivation. In line with Self-determination Theory literature, considering the basic psychological needs for relatedness and autonomy could assist with designing interventions, like creating a supportive work environment, to optimize motivation. This could improve professional wellbeing, service implementation and prevent possible adverse events. Future research is necessary to understand barriers and facilitators of clinical pharmacists' work motivation.