bluuebunny/crossref_metadata_2025 huggingface dataset:
Ijara as an Innovative Product in Agricultural Financing
Authors: Kantoroeva Aijamal K. , Toktomamatova Nurzat K.
Published: August 2021

The relevance of the study is due to the necessity to solve the problems of agricultural lending in the Kyrgyz Republic. The problems of financing and lending to agriculture are still urgent in the Kyrgyz Republic, therefore, specific financial instruments of Islamic banking, which are highly appreciated in the practise of other countries, are well suited for project financing, work in conditions of high uncertainty characteristic of agriculture in the Kyrgyz Republic. The purpose of the study was to identify alternative loan products for agricultural economic entities based on Islamic principles of financing in the Kyrgyz Republic. Research objectives: to provide brief information on the current state in the field of agricultural lending; give brief information on the development of Islamic principles of lending in the Kyrgyz Republic; define the concept and classification of Islamic banking instruments in agriculture; define the financial instrument “Ijara” and identify its advantages. Research methods: methods of the empirical level (studying of literature and other sources of information, observation, comparison), methods of the theoretical level (study and generalisation, analysis and synthesis). In the process of writing this article, Islamic banking instruments have been reviewed and classified. The concept of Ijara contract was considered, new modern technologies in the field of Islamic banking were investigated. The main distinctive principles of Islamic banking from the Western model of financial leasing were analysed. The credit history of agriculture and forestry of the Kyrgyz Republic was analysed.
ZiBuPiYin Recipe Prevented and Treated Cognitive Decline in ZDF Rats With Diabetes-Associated Cognitive Decline via Microbiota–Gut–Brain Axis Dialogue
Authors: Bi Tingting , Feng Ruiqi , Zhan Libin , Ren Weiming , Lu Xiaoguang
Published: August 2021

Gut microbiota is becoming one of the key determinants in human health and disease. Shifts in gut microbiota composition affect cognitive function and provide new insights for the prevention and treatment of neurological diseases. Diabetes-associated cognitive decline (DACD) is one of the central nervous system complications of type 2 diabetes mellitus (T2DM). ZiBuPiYin recipe (ZBPYR), a traditional Chinese medicine (TCM) formula, has long been used for the treatment of T2DM and prevention of DACD. However, the contribution of ZBPYR treatment to the interaction between the gut microbiota and metabolism for preventing and treating DACD remains to be clarified. Here, we investigate whether the gut microbiota plays a key role in ZBPYR-mediated prevention of DACD and treatment of T2DM via incorporating microbiomics and metabolomics, and investigate the links between the microbiota–gut–brain axis interaction and the efficacy of ZBPYR in ZDF rats. In the current study, we found that ZBPYR treatment produced lasting changes in gut microbiota community and metabolites and remotely affected hippocampus metabolic changes, thereby improving memory deficits and reversing β-amyloid deposition and insulin resistance in the brain of ZDF rats from T2DM to DACD. This may be related to a series of metabolic changes affected by gut microbiota, including alanine, aspartic acid, and glutamic acid metabolism; branched-chain amino acid metabolism; short-chain fatty acid metabolism; and linoleic acid/unsaturated fatty acid metabolism. In summary, this study demonstrates that prevention and treatment of DACD by ZBPYR partly depends on the gut microbiota, and the regulatory effects of bacteria-derived metabolites and microbiota–gut–brain axis are important protective mechanisms of ZBPYR.
The Application of Single-Cell RNA Sequencing in Mammalian Meiosis Studies
Authors: Peng Yiheng , Qiao Huanyu
Published: August 2021

Meiosis is a cellular division process that produces gametes for sexual reproduction. Disruption of complex events throughout meiosis, such as synapsis and homologous recombination, can lead to infertility and aneuploidy. To reveal the molecular mechanisms of these events, transcriptome studies of specific substages must be conducted. However, conventional methods, such as bulk RNA-seq and RT-qPCR, are not able to detect the transcriptional variations effectively and precisely, especially for identifying cell types and stages with subtle differences. In recent years, mammalian meiotic transcriptomes have been intensively studied at the single-cell level by using single-cell RNA-seq (scRNA-seq) approaches, especially through two widely used platforms, Smart-seq2 and Drop-seq. The scRNA-seq protocols along with their downstream analysis enable researchers to accurately identify cell heterogeneities and investigate meiotic transcriptomes at a higher resolution. In this review, we compared bulk RNA-seq and scRNA-seq to show the advantages of the scRNA-seq in meiosis studies; meanwhile, we also pointed out the challenges and limitations of the scRNA-seq. We listed recent findings from mammalian meiosis (male and female) studies where scRNA-seq applied. Next, we summarized the scRNA-seq analysis methods and the meiotic marker genes from spermatocytes and oocytes. Specifically, we emphasized the different features of the two scRNA-seq protocols (Smart-seq2 and Drop-seq) in the context of meiosis studies and discussed their strengths and weaknesses in terms of different research purposes. Finally, we discussed the future applications of scRNA-seq in the meiosis field.
CRISPR Toolbox for Genome Editing in Dictyostelium
Authors: Yamashita Kensuke , Iriki Hoshie , Kamimura Yoichiro , Muramoto Tetsuya
Published: August 2021

The development of new techniques to create gene knockouts and knock-ins is essential for successful investigation of gene functions and elucidation of the causes of diseases and their associated fundamental cellular processes. In the biomedical model organism Dictyostelium discoideum, the methodology for gene targeting with homologous recombination to generate mutants is well-established. Recently, we have applied CRISPR/Cas9-mediated approaches in Dictyostelium, allowing the rapid generation of mutants by transiently expressing sgRNA and Cas9 using an all-in-one vector. CRISPR/Cas9 techniques not only provide an alternative to homologous recombination-based gene knockouts but also enable the creation of mutants that were technically unfeasible previously. Herein, we provide a detailed protocol for the CRISPR/Cas9-based method in Dictyostelium. We also describe new tools, including double knockouts using a single CRISPR vector, drug-inducible knockouts, and gene knockdown using CRISPR interference (CRISPRi). We demonstrate the use of these tools for some candidate genes. Our data indicate that more suitable mutants can be rapidly generated using CRISPR/Cas9-based techniques to study gene function in Dictyostelium.
α1-nAchR-Mediated Signaling Through Lipid Raft Is Required for Nicotine-Induced NLRP3 Inflammasome Activation and Nicotine-Accelerated Atherosclerosis
Authors: Duan Fengqi , Zeng Cheng , Liu Sijun , Gong Jianfeng , Hu Jia , Li Hongyu , Tan Hongmei
Published: August 2021

Background

Nicotine exerts direct effects on multiple cell types in the cardiovascular system by associating with its high-affinity nicotinic acetylcholine receptors (nAchRs). Lipid raft is a membrane microdomain that recruits various receptors and signaling molecules for coordinating cellular immune response and many others signaling processes. Here, we aim to identify the essential role of lipid raft in mediating nicotine-triggered inflammatory and nicotine-accelerated atherosclerosis, and to figure out the specific receptor of nicotine-induced Nod-like receptor protein 3 (NLRP3) inflammasome activation in macrophage.

Methods and Results

ApoE–/– mice were fed with a high-fat diet to build atherosclerosis model. Methyl-β-cyclodextrin was used to interrupt intact lipid raft. We confirmed that nicotine triggered NLRP3 inflammasome activation and induced macrophage migration into atherosclerotic plaque, thus accelerated atherosclerosis in apoE–/– mice fed with a high-fat diet. Mechanically, nicotine increased the expression of α1-nAChR and stimulated the accumulation of α1-nAChR in lipid raft, leading to NLRP3 inflammasome activation in macrophage. Conversely, silencing of α1-nAChR in macrophage sufficiently blocked the pro-inflammasome activation effect of nicotine, indicating that α1-nAChR was the specific receptor for nicotine in triggering NLRP3 inflammasome in macrophage. Furthermore, both the destruction of lipid raft by methyl-β-cyclodextrin and the interference of lipid raft clustering by silencing acid sphingomyelinase reversed nicotine-induced NLRP3 inflammasome activation by reducing the accumulation of α1-nAChR in lipid raft in macrophage, suggesting lipid raft–mediated accumulation of α1-nAChR was the key event in regulating the pro-inflammatory effects of nicotine in macrophage. Importantly, nicotine-induced NLRP3 inflammasome activation and macrophage migration into atherosclerotic plaque were reversed by methyl-β-cyclodextrin, making a significant improvement for atherosclerosis in apoE–/– mice fed with a high-fat diet.

Conclusion

α1-nAChR-mediated signaling through lipid raft is required for NLRP3 inflammasome activation and pro-atherosclerotic property of nicotine.
Facile Synthesis and Electrochemical Studies of Mn2O3/Graphene Composite as an Electrode Material for Supercapacitor Application
Authors: Mustafa Ghulam , Mehboob Gohar , Khisro Said Nasir , Javed Muhammad , Chen Xinman , Ahmed M. Shafiq , Ashfaq J. M. , Asghar G. , Hussain Shahnwaz , Rashid Amin ur , Mehboob Ghazanfar
Published: August 2021

A simplified sol-gel method that can be scaled up for large-scale production was adopted for the preparation of manganese oxide nanocrystals. Prepared Mn2O3 exhibited micron-sized particles with a nanoporous structure. In the present study, a simple and low-cost strategy has been employed to fabricate nanoporous Mn2O3 with an increased surface area for an electrode/electrolyte interface that improved the conduction of Mn2O3 material. The crystal phase and morphology of the prepared material was investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). The prepared electrode materials were deposited on a nickel foam substrate to investigate the electrochemical properties. The galvanostatic charge/discharge (GCD), cyclic voltammetry (CV), and complex impedance studies confirmed excellent specific capacitance and capacitive behavior of the prepared material. The synthesized Mn2O3/graphene composites exhibited an excellent specific capacitance of 391 F/g at a scan rate of 5 mV/S. Moreover, a specific capacitance of 369 F/g was recorded at a current density of 0.5 A/g using the galvanostatic charge/discharge test. The high porosity of the materials provided a better electrolyte-electrode interface with a larger specific area, thus suggesting its suitability for energy storage applications.
Secure Dynamic State Estimation for Cyber Security of AC Microgrids
Authors: Fooladivanda Dariush , Hu Qie , Chang Young Hwan
Published: August 2021

A timely, accurate, and secure dynamic state estimation is needed for reliable monitoring and efficient control of microgrids. The synchrophasor technology enables system operators to obtain synchronized measurements in real-time and to develop dynamic state estimators for monitoring and control of microgrids. However, in practice, sensor measurements can be corrupted or attacked. In this study, we consider an AC microgrid comprising several synchronous generators and inverter-interface power supplies, and focus on securely estimating the dynamic states of the microgrid from a set of corrupted data. We propose a secure dynamic state estimator which allows the microgrid operator to reconstruct the dynamic states of the microgrid from a set of attacked or corrupted data without any assumption on attacks or corruptions. Finally, we consider an AC microgrid with the same topology as the IEEE 33-bus distribution system, and show that the proposed secure estimation algorithm can accurately reconstruct the attack signals.
The Potential Therapeutic Role of Celastrol in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Ajmal Maryam , Ajmal Aisha , Huang Lei , Zeng Lingfang
Published: August 2021

Analysis of left ventricular systolic dysfunction remained at the centre of heart failure research for many years (also known as heart failure with reduced ejection fraction, HFrEF). Although more than 50% of all heart failure patients experience a form of heart failure characterised by preserved ejection fraction (HFpEF), the pathophysiological mechanisms leading to this form of heart failure remain not well-understood. Several evidence-based treatments for HFrEF are in routine use, but there are limited evidence-based therapies for HFpEF. The effects of these remain controversial, with current treatment options being limited to managing the associated symptoms and conditions. Accumulating evidence demonstrates that pro-inflammatory and oxidative stress pathways play key roles in the development and progression of HFpEF, such as the Unfolded Protein Response (UPR) and inducible nitric oxide synthase. Celastrol, derived from medicinal plants, is a bioactive compound with strong anti-inflammatory properties, which could deem it as fruitful in overcoming the effects of such dysregulated UPR. This literature review therefore focuses on Celastrol's anti-inflammatory and antioxidant activities, alongside its other potential therapeutic activities, and its ability to impede the pathways that are thought to be involved in the development of HFpEF, such as the JAK2/STAT pathway, to elucidate the potential therapeutic role of this bioactive compound, in the treatment of HFpEF.
Middle Ordovician Upwelling-Related Ironstone of North Wales: Coated Grains, Ocean Chemistry, and Biological Evolution
Authors: Dunn Sarah K. , Pufahl Peir K. , Murphy J. Brendan , Lokier Stephen W.
Published: August 2021

Middle Ordovician phosphatic ironstone of the Welsh Basin provides new insight into the paleoenvironmental significance of ironstone and Ordovician ocean chemistry. Deposition occurred in a back-arc basin along the southern margin of Avalonia as the Rheic Ocean opened to the south. Ironstone is interpreted to have accumulated as part of an aggradational parasequence on a storm-dominated shelf with coastal upwelling. This parasequence has a laminated pyritic mudstone base that grades upward into variably bioturbated mudstone and coated grain-rich, intraclastic ironstone, which is overlain in turn by cross-stratified grainstone composed entirely of coated Fe grains. A coarser clastic parasequence composed of more proximal lithofacies rests conformably above and suggests the contact between the two parasequences is a maximum flooding surface marking the onset of highstand conditions. Lithofacies associations suggest that sustained coastal upwelling created a wedge of nutrient-rich, ferruginous seawater on the middle shelf that stimulated high surface ocean productivities. Large, coated Fe grains (granule size) composed of discontinuous and concentric carbonate fluorapatite, hematite, and chamosite cortical layers record fluctuations in pore water Eh that are interpreted to have been related to changes in upwelling intensity and intermittent storm reworking of the seafloor. Results support an emerging model for Ordovician ironstone underpinned by the development of ferruginous bottom water that was periodically tapped by coastal upwelling. Expanding, semi-restricted seaways such as the Rheic Ocean were ideal locations for the ponding of this anoxic, hydrothermally enriched seawater, especially during the early Paleozoic when the deep ocean was variably and inconsistently oxygenated. The coincidence of ironstone depositional episodes with graptolite diversification events suggests that, in addition to Fe, the sustained supply of upwelling-related P may have driven the radiation of some planktonic ecosystems during the Great Ordovician Biodiversification Event. Concomitant minor extinctions of benthic trilobites occurred as these ferruginous waters impinged on the shelf.
Perception of Online Learning Among Students From India Set Against the Pandemic
Authors: Bast Felix
Published: August 2021

India is the second-most populous country in the world. There had been a tremendous shift towards online learning through Indian Government’s digital initiatives in general, and during COVID-19 lockdown in particular. An online self-report survey (n = 1,318) was conducted to assess students’ perception of online learning in this changed situation in comparison with traditional classroom learning. The study analysed eight independent variables on student’s perception towards online learning, viz., gender, nature of the settlement, economic background, religiosity, primary electronic device, technology-receptiveness, age, and educational institution, with each of these variables forming respective research hypotheses. Results revealed several exciting facets of students’ perceptions. Receptiveness towards online learning was significantly higher for students from urban areas compared with rural areas. Possible reasons for these results are discussed, impediments to student’s motivation with digital education are identified and the findings are contextualized in a broader perspective.
A Facile Procedure for One-Pot Stable Conjugation of Two Proglucagon Cysteine-Containing Peptide Analogs
Authors: He Rongjun , Mowery Stephanie A. , Chabenne Joseph , Finan Brian , Mayer John P. , DiMarchi Richard D.
Published: August 2021

Optimization of peptides for therapeutic purposes often includes chemical conjugation or modification with substituents that serve to broaden pharmacology or improve pharmacokinetics. We report a convenient and rapid procedure for one-pot, site-specific conjugation of two cysteine-containing peptides that utilizes a bivalent linker comprising maleimide and iodoacetyl functional groups. Following maleimide-mediated peptide conjugation the linker was converted from an unstable thiosuccinimide to a stable thioether bond suitable for biological study by mild aqueous hydrolysis. The procedure is exemplified by peptide-peptide, peptide-small molecule, and peptide-fatty acid conjugations. The method provides a facile approach to search for enhanced biological outcomes through additive and sustained peptide pharmacology unencumbered by the prospect of chemical rearrangement in the course of biological study.
Experimental Study on the Effect of Combination of Thermodynamic Inhibitors’ and Kinetic Inhibitors’ Hydrate Inhibition
Authors: Gao Yonghai , Wang Yanlong , Xin Guizhen , Wang Xiangdong , Yue Cheng , Chen Litao
Published: August 2021

In deepwater gas well testing, the high-pressure and low-temperature environment in the wellbore provides conditions for hydrate formation. When the thermodynamic inhibitor is used, it needs a large amount and is difficult to inject. Low-dose hydrate inhibitors such as kinetic inhibitors are rarely used in high supercooling and natural gas–dominated environments. The mixed use of thermodynamic inhibitors and kinetic inhibitors provides a new way. By simulating the wellbore temperature and pressure conditions during the deepwater gas well testing, the inhibiting effect of the mixtures of PVCap and methanol with various concentrations was experimentally tested by using rocking cells with a step-cooling method at 21MPa. The effect of PVCap and its mixture with methanol on hydrate plugging was evaluated by monitoring the movement of slider in the rocking cell. The results showed that 5 wt%, 16 wt%, and 20 wt% methanol mixed with 0.5 wt% PVCap could prolong the induction time, and the higher the methanol concentration, the longer the hydrate induction time. Among them, the best combination of 20wt% methanol and 0.5wt% PVCap can inhibit the hydrate for 379 min. The hydrate was formed but did not block the rocking cell, indicating that the combination of PVCap and methanol could not only prolong the hydrate formation time but also avoid the blockage after hydrate formation. The hydrate formation rate with various inhibitor concentrations was calculated; it may provide some guidance for making a shut-in plan for on-site wells.
Charging Strategy for Electric Vehicles Considering Consumer Psychology and Trip Chain
Authors: Gou Jiwei , Lin Changsheng , Li Jun , Geng Bo , Li Zhi , Cao Yang , Li Yang , Bao Yuqing
Published: August 2021

As a kind of movable storage device, the electrical vehicles (EVs) are able to support load shaving through orderly charging. The existing researches mostly focus on the design of EVs charging control technology with little consideration of trip-chain-based consumer psychology of EV owners. To fill this gap, this article proposes a price-based orderly charging strategy for EVs considering both consumer psychology and trip chain. Then, the load shaving problem is transformed into a multiobjective optimization problem, to minimize peak-to-valley difference and network loss. A time-of-use price optimization model based on consumer psychology is established to describe the charging behavior of EV owners influenced by electricity price. Finally, the examples verify the feasibility of the proposed strategy by comparing the impact of EVs connected to grid under different ratios, different load transfer rates, and different scenarios.
Engineering an Ecological Civilization Along Shanghai’s Main Waterfront and Coastline: Evaluating Ongoing Efforts to Construct an Urban Eco-Network
Authors: Den Hartog H.
Published: August 2021

Recent ecological civilization policies make clear that China is willing to play a leading role in a sustainable green transition. But there are still discrepancies in definitions, appreciation and evaluation of ecological assets. This paper examines how Shanghai works on a sustainability transition, with a focus on its main urban waterfronts and coastline, in the context of an extremely high population concentration, world’s highest real estate values, and continuous urban development pressure. This paper will mobilize insights from the academic field of sustainability transitions to show how urban planning and design ambitions are translated into realities on the ground. In its latest Shanghai Master Plan (2017-2035), the city commits itself to set an example for other Chinese cities. Moreover, Shanghai’s city leaders want to inspire and push cities internationally to become more adaptable and resilient, both in the Global South and Global North. The spatially most radical action to realize this ambition is to create “a green and open eco-network” with 60% of Shanghai’s municipal territory to be used for ecological purposes, mostly wetlands. This paper will examine three urban planning and design projects that have key positions within this eco-network. On all three sites there are land-use conflicts, between urban development and ecological (re-)development. The first case is the recent transformation of no less than 120 km of former industrial dominated waterfront along the Huangpu River, of which half was completed between 2016 and 2021. The second case, Nanhui Coastal Wetland Reserve with adjacent Lingang New City; and the third case, Chongming Eco-Island, started both around the millennium and had a 2020 planning horizon. After learning lessons from their previous sustainable innovation journeys these latter two projects entered a new phase as part of the eco-network. The paper concludes with seven practical recommendations aimed to reduce discrepancies between expectations and their implementation in practice: 1) use clear definitions; 2) co-create a shared vision for the future; 3) stop building on vulnerable locations; 4) create conditions of social learning; 5) supervision needs to go beyond planning boundaries; 6) step beyond an anthropocentric approach; and 7) foster a more experimental approach.
Increased Neutrophil Aging Contributes to T Cell Immune Suppression by PD-L1 and Arginase-1 in HIV-1 Treatment Naïve Patients
Authors: Liu Kai , Huang Hui-Huang , Yang Tao , Jiao Yan-Mei , Zhang Chao , Song Jin-Wen , Zhang Ji-Yuan , Zhou Chun-Bao , Yuan Jin-Hong , Cao Wen-Jing , Mu Xiu-Ying , Zhou Ming-Ju , Li Hua-Jie , Shi Ming , Xu Ruonan , Wang Fu-Sheng
Published: August 2021

Neutrophils are characterized by their heterogeneity. They fight against pathogens and are involved in tissue injury repair and immune system regulation. Neutrophils have an extremely short life span in the peripheral blood and undergo aging after being released from the bone marrow. The over-aggregation of aged neutrophils is associated with phenotypical and functional changes. Here, we aimed to investigate the dynamics of neutrophil aging and its relationship with T cell exhaustion in HIV-1 infection, as they are not well understood. In this study, we enrolled 23 treatment naïve (TN) patients, 23 individuals that had received antiretroviral therapy (ART), and 21 healthy controls (HC). In these cohorts, we measured the degree of neutrophil aging, and its possible correlation with T cell dysfunction. In TN patients, peripheral neutrophils showed a more distinct aging phenotype and were over-activated compared to those in ART-treated patients. The degree of neutrophil aging was positively correlated with HIV-1 RNA viral load and negatively correlated with CD4+ T cell count. Moreover, aged neutrophils had impaired reactive oxygen species (ROS) production after lipopolysaccharide (LPS) stimulation, and were characterized by increased PD-L1 and arginase-1 expression in a time-dependent manner. Aged neutrophils demonstrated an increased inhibition of IFN-γ and TNF-α secretion by CD8+ T cell compared to non-aged neutrophils. The inhibition effect could be partially reversed by blocking PD-L1 and arginase-1 in vitro, and LPS was identified as an important activator of neutrophil aging. These results provide evidence that dampening neutrophil aging may provide a novel approach to recover T cell dysfunction in patients with HIV-1 infection.
Selective Binding of Heparin/Heparan Sulfate Oligosaccharides to Factor H and Factor H-Related Proteins: Therapeutic Potential for C3 Glomerulopathies
Authors: Loeven Markus A. , Maciej-Hulme Marissa L. , Yanginlar Cansu , Hubers Melanie C. , Kellenbach Edwin , de Graaf Mark , van Kuppevelt Toin H. , Wetzels Jack , Rabelink Ton J. , Smith Richard J. H. , van der Vlag Johan
Published: August 2021

Complement dysregulation is characteristic of the renal diseases atypical hemolytic uremic syndrome (aHUS) and complement component 3 glomerulopathy (C3G). Complement regulatory protein Factor H (FH) inhibits complement activity, whereas FH-related proteins (FHRs) lack a complement regulatory domain. FH and FHRs compete for binding to host cell glycans, in particular heparan sulfates (HS). HS is a glycosaminoglycan with an immense structural variability, where distinct sulfation patterns mediate specific binding of proteins. Mutations in FH, FHRs, or an altered glomerular HS structure may disturb the FH : FHRs balance on glomerular endothelial cells, thereby leading to complement activation and the subsequent development of aHUS/C3G. In this study, we aimed to identify specific HS structures that could specifically compete off FHRs from HS glycocalyx (HSGlx), without interfering with FH binding. FH/FHR binding to human conditionally immortalized glomerular endothelial cells (ciGEnCs) and HSGlxpurified from ciGEnC glycocalyx was assessed. HS modifications important for FH/FHR binding to HSGlxwere analyzed using selectively desulfated heparins in competition with purified HSGlx. We further assessed effects of heparinoids on FHR1- and FHR5-mediated C3b deposition on ciGEnCs. In the presence of C3b, binding of FH, FHR1 and FHR5 to ciGEnCs was significantly increased, whereas binding of FHR2 was minimal. FHR1 and 5 competitively inhibited FH binding to HSGlx, leading to alternative pathway dysregulation. FHR1 and FHR5 binding was primarily mediated by N-sulfation while FH binding depended on N-, 2-O- and 6-O-sulfation. Addition of 2-O-desulfated heparin significantly reduced FHR1- and FHR5-mediated C3b deposition on ciGEnCs. We identify 2-O-desulfated heparin derivatives as potential therapeutics for C3G and other diseases with dysregulated complement.
In Vitro Modelling of Respiratory Virus Infections in Human Airway Epithelial Cells – A Systematic Review
Authors: Rijsbergen Laurine C. , van Dijk Laura L. A. , Engel Maarten F. M. , de Vries Rory D. , de Swart Rik L.
Published: August 2021

Respiratory tract infections (RTI) are a major cause of morbidity and mortality in humans. A large number of RTIs is caused by viruses, often resulting in more severe disease in infants, elderly and the immunocompromised. Upon viral infection, most individuals experience common cold-like symptoms associated with an upper RTI. However, in some cases a severe and sometimes life-threatening lower RTI may develop. Reproducible and scalablein vitroculture models that accurately reflect the human respiratory tract are needed to study interactions between respiratory viruses and the host, and to test novel therapeutic interventions. Multiplein vitrorespiratory cell culture systems have been described, but the majority of these are based on immortalized cell lines. Although useful for studying certain aspects of viral infections, such monomorphic, unicellular systems fall short in creating an understanding of the processes that occur at an integrated tissue level. Novelin vitromodels involving primary human airway epithelial cells and, more recently, human airway organoids, are now in use. In this review, we describe the evolution ofin vitrocell culture systems and their characteristics in the context of viral RTIs, starting from advances after immortalized cell cultures to more recently developed organoid systems. Furthermore, we describe how these models are used in studying virus-host interactions, e.g. tropism and receptor studies as well as interactions with the innate immune system. Finally, we provide an outlook for future developments in this field, including co-factors that mimic the microenvironment in the respiratory tract.
Ferroptosis: A Trigger of Proinflammatory State Progression to Immunogenicity in Necroinflammatory Disease
Authors: Li Jing-yan , Yao Yong-ming , Tian Ying-ping
Published: August 2021

Until recently, necrosis is generally regarded as traumatic cell death due to mechanical shear stress or other physicochemical factors, while apoptosis is commonly thought to be programmed cell death, which is silent to immunological response. Actually, multiple modalities of cell death are programmed to maintain systematic immunity. Programmed necrosis, such as necrosis, pyroptosis, and ferroptosis, are inherently more immunogenic than apoptosis. Programmed necrosis leads to the release of inflammatory cytokines, defined as danger-associated molecular patterns (DAMPs), resulting in a necroinflammatory response, which can drive the proinflammatory state under certain biological circumstances. Ferroptosis as a newly discovered non-apoptotic form of cell death, is characterized by excessive lipid peroxidation and overload iron, which occurs in cancer, neurodegeneration, immune and inflammatory diseases, as well as ischemia/reperfusion (I/R) injury. It is triggered by a surplus of reactive oxygen species (ROS) induced in an imbalanced redox reaction due to the decrease in glutathione synthesis and inaction of enzyme glutathione peroxidase 4 (GPX4). Ferroptosis is considered as a potential therapeutic and molecular target for the treatment of necroinflammatory disease, and further investigation into the underlying pathophysiological characteristics and molecular mechanisms implicated may lay the foundations for an interventional therapeutic strategy. This review aims to demonstrate the key roles of ferroptosis in the development of necroinflammatory diseases, the major regulatory mechanisms involved, and its potential as a therapeutic target.
A Novel Measurement-Based Model for Calculating Diffusive Fluxes Across Substrate-Water Interfaces of Marine Aggregates, Sediments and Biofilms
Authors: Moradi Nasrollah , Klawonn Isabell , Iversen Morten H. , Wenzhöfer Frank , Grossart Hans-Peter , Ploug Helle , Fischer Gerhard , Khalili Arzhang
Published: August 2021

Our understanding of the small-scale processes that drive global biogeochemical cycles and the Earth’s climate is dependent on accurate estimations of interfacial diffusive fluxes to and from biologically-active substrates in aquatic environments. In this study, we present a novel model approach for accurate calculations of diffusive fluxes of dissolved gases, nutrients, and solutes from concentration profiles measured across the substrate-water interfaces using microsensors. The model offers a robust computational scheme for automatized determination of the interface position and enables precise calculations of the interfacial diffusive fluxes simultaneously. In contrast to other methods, the new approach is not restricted to any particular substrate geometry, does not requirea prioridetermination of the interface position for the flux calculation, and, thus, reduces the uncertainties in calculated fluxes arising from partly subjective identification of the interface position. In addition, it is robust when applied to measured profiles containing scattered data points and insensitive to reasonable decreases of the spatial resolution of the data points. The latter feature allows for significantly reducing measurement time which is a crucial factor forin situexperiments.
Variation of Isoprenoid GDGTs in the Stratified Marine Water Column: Implications for GDGT-Based TEX86 Paleothermometry
Authors: Guo Jinqiang , Yuan Huamao , Song Jinming , Qu Baoxiao , Xing Jianwei , Wang Qidong , Li Xuegang , Duan Liqin , Li Ning , Wang Yingxia
Published: August 2021

Isoprenoid glycerol dialkyl glycerol tetraethers (isoGDGTs) derived from archaea are lipid biomarkers that exhibit high sensitivity to changes in water temperature, leading to the widespread application of the isoGDGT-based tetraether index of 86 carbon atoms (TEX86) in surface seawater temperature (SST) reconstruction. However, there remain some uncertainties regarding the robustness of TEX86 under changing water conditions (e.g., variations in water depth, oxygen and pH). Here, we analyzed isoGDGTs in suspended particles at different depths of the East China Sea (ECS) during summer 2020, aiming to constrain the applicability of the TEX86 proxy in coastal waters. Our data showed that the isoGDGTs were mainly derived from planktonic Thaumarchaeota, as revealed by the low ratio of GDGT-0/crenarchaeol (<0.5). The vertical distribution of isoGDGT concentration depicted a downward increase from the surface to the bottom. This observation was likely shaped by Thaumarchaeota, which regulate the extent of ammonia oxidation based on the availability of ammonium. The occurrence of maximal isoGDGT concentrations in the bottom layer suggests that the isoGDGTs in sediments are mainly controlled by bottom archaeal production rather than surface archaeal production. By reanalyzing the published isoGDGT data of surface sediments in the ECS inner shelf, we found that the sedimentary TEX86 relates much better to the annual mean bottom seawater temperature (BST) than to the annual mean SST, indicating that sedimentary TEX86 is more inclined to be a proxy for the BST in the shallow ECS. In addition, the positive bias of TEX86 driven by low dissolved oxygen and low pH was observed under the pycnocline, indicating that the application of TEX86 to reconstruct seawater temperature should be carefully appraised in coastal environments with strong water column stratification.
Initial Renal Function (eGFR) Is a Prognostic Marker of Severe Acute Pancreatitis: A Cohort-Analysis of 1,224 Prospectively Collected Cases
Authors: Tod Pál , Farkas Nelli , Németh Dávid , Szénási Gábor , Vincze Áron , Hágendorn Roland , Czakó László , Illés Dóra , Izbéki Ferenc , Dunás-Varga Veronika , Papp Mária , Hamvas József , Varga Márta , Gombos Katalin , Nagy Tamás , Márton Zsolt , Faluhelyi Nándor , Török Imola , Ince Ali Tüzün , Galeev Shamil , Hegyi Péter Jenő , Szentesi Andrea , Párniczky Andrea , Szakács Zsolt , Hegyi Péter , Hamar Péter
Published: August 2021

Background: Acute pancreatitis (AP) is a life-threatening disease. We aimed to explore the prognostic relevance of renal function based on estimated glomerular filtration rate (eGFR).

Methods: A prospective registry of AP patients was established by the Hungarian Pancreatic Study Group. Data of 1,224 consecutive patients were collected between 2012 and 2017. Patients were divided into 3 groups according to their eGFR measured within 24 h of hospitalization: normal renal function: >90 mL/min, mild to moderate renal functional impairment: 30–90 mL/min and severe renal dysfunction: <30 mL/min. Associations of eGFR with outcome (survival, length of hospitalization, AP severity, blood glucose), inflammatory markers (erythrocyte sedimentation rate, white blood cell count), anemia and organ failure (heart, kidney, liver) were analyzed.

Results: Death, longer hospitalization and severe AP, but not the cause of AP, were significantly associated with lower eGFR. The inflammatory markers (CRP, WBC count) but not anemia (Hb, Htk) were closely associated with severe renal dysfunction. Renal function was associated with heart and renal failure but not with other complications of AP such as respiratory failure, local pancreatic complications, diabetes or peptic ulcer. eGFR was not associated with liver damage (ALAT, γ-GT) or liver function (serum bilirubin) although biliary complications, alcohol and metabolic syndrome were the most common etiologies of AP.

Conclusions: Our study suggests a useful prognostic value of initial eGFR in AP patients. Even mild eGFR reduction predicted mortality, severity of AP and the length of hospitalization. Thus, precise evaluation of renal function should be considered for assessing AP severity and outcome.
Immune System Disequilibrium—Neutrophils, Their Extracellular Traps, and COVID-19-Induced Sepsis
Authors: Keane Colm , Coalter Matthew , Martin-Loeches Ignacio
Published: August 2021

Equilibrium within the immune system can often determine the fate of its host. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. Immune dysregulation remains one of the main pathophysiological components of SARS-CoV-2-associated organ injury, with over-activation of the innate immune system, and induced apoptosis of adaptive immune cells. Here, we provide an overview of the innate immune system, both in general and relating to COVID-19. We specifically discuss “NETosis,” the process of neutrophil release of their extracellular traps, which may be a more recently described form of cell death that is different from apoptosis, and how this may propagate organ dysfunction in COVID-19. We complete this review by discussing Stem Cell Therapies in COVID-19 and emerging COVID-19 phenotypes, which may allow for more targeted therapy in the future. Finally, we consider the array of potential therapeutic targets in COVID-19, and associated therapeutics.
Early Origins of Psoriatic Arthritis: Clinical, Genetic and Molecular Biomarkers of Progression From Psoriasis to Psoriatic Arthritis
Authors: Pennington Stephen R. , FitzGerald Oliver
Published: August 2021

Greater than 90% of patients with psoriatic arthritis (PsA) first develop their arthritis on a background of known psoriasis (Pso). Thus, having skin/nail Pso certainly is an important risk factor for PsA but as PsA develops in <30% of those affected with Pso, the presence of Pso alone is insufficient as a means of identifying which patients with Pso will develop PsA. It is hoped that with further molecular assessment of Pso patients who do not have any evidence of inflammatory musculoskeletal disease compared to those with early PsA features, that the “at risk” profile of Pso patients destined to develop PsA can be refined such that disease prevention studies can be designed and a new era of treatment for PsA can emerge. In this article, the early stages in the development of PsA are outlined and what is currently known about clinical features, genetic factors and soluble or tissue biomarkers associated with the development of PsA in patients with Pso is reviewed in detail. Finally, proposals are outlined regarding the approaches required in order to address this important research area.
Adaptive Laboratory Evolution of Microalgae: A Review of the Regulation of Growth, Stress Resistance, Metabolic Processes, and Biodegradation of Pollutants
Authors: Zhang Bo , Wu Jiangyue , Meng Fanping
Published: August 2021

Adaptive laboratory evolution (ALE) experiments are a serviceable method for the industrial utilization of the microalgae, which can improve the phenotype, performance, and stability of microalgae to obtain strains containing beneficial mutations. In this article, we reviewed the research into the microalgae ALE test and assessed the improvement of microalgae growth, tolerance, metabolism, and substrate utilization by ALE. In addition, the principles of ALE and the key factors of experimental design, as well as the issues and drawbacks of the microalgae ALE method were discussed. In general, improving the efficiency of ALE and verifying the stability of ALE resulting strains are the primary problems that need to be solved in future research, making it a promising method for the application of microalgae biotechnology.
Deliberative Decision-Making in Macaques Removes Reward-Driven Response Vigor
Authors: Daddaoua Nabil , Jedema Hank P. , Bradberry Charles W.
Published: August 2021

Most of our daily decisions are governed by one of two systems: an impulsive system driving instantaneous decisions and a deliberative system driving thoughtful ones. The impulsive system reacts to immediately available concrete rewards. In contrast, the deliberative system reacts to more delayed rewards and/or punishments, which imposes consideration of longer-term choice consequences. Contingency management for addiction treatment is hypothesized to engage deliberative processes. Ultimately, in both decision-making situations, an action is needed to enact the decision. Whether those actions differ in implementation is an open question whose answer could inform as to whether distinct neural systems are engaged. To explore whether there is evidence of separate mechanisms between deliberated and immediate choices, we trained monkeys to perform a decision-making task where they made a choice on a touch screen between two visual cues predicting different amounts of reward. In immediate choice (IC) trials, the cues appeared at the final response locations where subjects could immediately touch the chosen cue. In deliberated choice (DC) trials, compound cues appeared orthogonally to the response locations. After a delay, allowing for decision formation, an identifying cue component was displaced to the randomly assigned response locations, permitting subjects to reach for the chosen cue. Both trial types showed an effect of cue value on cue selection time. However, only IC trials showed an effect of the competing cue on response vigor (measured by movement duration) and a reach trajectory that deviated in the direction of the competing cue, suggesting a decision reexamination process. Reward modulation of response vigor implicates dopaminergic mechanisms. In DC trials, reach trajectories revealed a commitment to the chosen choice target, and reach vigor was not modulated by the value of the competing cue. Our results suggest that choice–action dynamics are shaped by competing offers only during instantaneous, impulsive choice. After a deliberated decision, choice–action dynamics are unaffected by the alternative offer cue, demonstrating a commitment to the choice. The potential relevance to contingency management is discussed.
Individual Differences in Conditioned Fear and Extinction in Female Rats
Authors: Tryon Sarah C. , Sakamoto Iris M. , Kellis Devin M. , Kaigler Kris F. , Wilson Marlene A.
Published: August 2021

The inability to extinguish a traumatic memory is a key aspect of post-traumatic stress disorder (PTSD). While PTSD affects 10–20% of individuals who experience a trauma, women are particularly susceptible to developing the disorder. Despite this notable female vulnerability, few studies have investigated this particular resistance to fear extinction observed in females. Similar to humans, rodent models of Pavlovian fear learning and extinction show a wide range of individual differences in fear learning and extinction, although female rodents are considerably understudied. Therefore, the present study examined individual differences in fear responses, including freezing behavior and ultrasonic vocalizations (USVs), of female Long–Evans rats during acquisition of fear conditioning and cued fear extinction. Similar to prior studies in males, female rats displayed individual variation in freezing during cued fear extinction and were divided into extinction competent (EC) and extinction resistant (ER) phenotypes. Differences in freezing between ER and EC females were accompanied by shifts in rearing during extinction, but no darting was seen in any trial. Freezing behavior during fear learning did not differ between the EC and ER females. Vocalizations emitted in the 22 and 50 kHz ranges during fear learning and extinction were also examined. Unlike vocalizations seen in previous studies in males, very few 22 kHz distress vocalizations were emitted by female rats during fear acquisition and extinction, with no difference between ER and EC groups. Interestingly, all female rats produced significant levels of 50 kHz USVs, and EC females emitted significantly more 50 kHz USVs than ER rats. This difference in 50 kHz USVs was most apparent during initial exposure to the testing environment. These results suggest that like males, female rodents show individual differences in both freezing and USVs during fear extinction, although females appear to vocalize more in the 50 kHz range, especially during initial periods of exposure to the testing environment, and emit very few of the 22 kHz distress calls that are typically observed in males during fear learning or extinction paradigms. Overall, these findings show that female rodents display fear behavior repertoires divergent from males.