bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic and ChIP-seq Integrative Analysis Identifies KDM5A-Target Genes in Cardiac Fibroblasts
Authors: Jiang Yiyao , Zhang Xu , Wei Ting , Qi Xianjie , Abba Isah Amir , Zhang Nana , Chen Yao , Wang Ran , Shi Chao
Published: July 2022

Cardiac fibrosis is a common pathological feature in cardiac remodeling. This study aimed to explore the role of KDM5A in cardiac fibrosis via bioinformatics analysis. Cardiac fibroblasts (CFs) were harvested and cultured from 10 dilated cardiomyopathy (DCM) patients who underwent heart transplantation. Western blotting was applied to verify that KDM5A is regulated by angiotensin II (Ang II) via the PI3k/AKT signaling pathway. The differentially expressed genes (DEGs) were analyzed by transcriptomics. ChIP-seq and ChIP-qPCR were used to identify the genes bound by KDM5A. In integrative analysis, weighted gene coexpression network analysis (WGCNA) was performed to identify highly relevant gene modules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the key genes in modules. The STRING database, Cytoscape, and MCODE were applied to construct the protein–protein interaction (PPI) network and screen hub genes. To verify the expression of DEGs regulated by KDM5A, Western blotting and immunofluorescence were performed in myocardial tissue samples. Immunofluorescence verified the vimentin positivity of CFs. Ang II upregulated the expression of KDM5A in CFs via the PI3K/AKT signaling pathway. GO analysis of DEGs indicated that regulation of vasoconstriction, extracellular region, and calcium ion binding were enriched when KDM5A interfered with CPI or Ang II. KEGG analysis of the DEGs revealed the involvement of ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, cell adhesion, and arrhythmogenic right ventricular cardiomyopathy pathways. Three hub genes (IGF1, MYH11, and TGFB3) were identified via four different algorithms. Subsequent verification in patient samples demonstrated that the hub genes, which were regulated by KDM5A, were downregulated in DCM samples. KDM5A is a key regulator in the progression of cardiac fibrosis. In this successful integrative analysis, IGF1, MYH11, and TGFB3 were determined to be coordinately expressed to participate in cardiac fibrosis.
Prognostic Value of Modified Model for End-Stage Liver Disease Score in Patients Undergoing Isolated Tricuspid Valve Replacement
Authors: Xu Hongjie , Wang He , Chen Shisong , Chen Qian , Xu Tianyu , Xu Zhiyun , Sun Yangyong
Published: July 2022

Objective

Though the prognostic value of the model for end-stage liver disease (MELD) score in tricuspid surgery was confirmed, the unstable international normalized ratio (INR) may affect the evaluation effectiveness of the MELD score for isolated tricuspid valve replacement (ITVR). The aim of the study was to assess the prognostic value of modified MELD for ITVR.

Methods and Results

A total of 152 patients who underwent ITVR were evaluated. The adverse outcome was defined as in-hospital mortality after surgery. The receiver operating characteristic (ROC) curve analysis demonstrated that a modified MELD score with albumin replacing INR (MELD-albumin) score presented well prognostic value [area under the curve (AUC) = 0.731, p = 0.006] for in-hospital mortality. Through Cox regression and further interval validation, the MELD-albumin score was identified as an independent predictor for in-hospital mortality. The optimal cutoff value of MELD-albumin was identified as 8.58 through maximally selected log-rank statistics. In addition, restricted cubic spline analysis demonstrated the linear inverse relationship between MELD-albumin and hazard ratio (HR) for in-hospital mortality. Kaplan–Meier analysis illustrated that in-hospital mortality was increased significantly in the high MELD-albumin (MELD-albumin ≥8.58) group than in the low MELD-albumin group (MELD-albumin <8.58; p < 0.001). Furthermore, high MELD-albumin was associated with lower body mass index (BMI), the incidence of lower extremities edema and moderate drinking history, and the MELD-albumin score was correlated with the value of aspartate transaminase (AST), alanine transaminase (ALT), and albumin. Furthermore, the incidence of renal failure (p = 0.003) and pulmonary infection (p = 0.042) was increased significantly in the high MELD-albumin group.

Conclusion

The MELD-albumin score could provide prognostic value for ITVR. In addition, the MELD-albumin score was useful in risk stratification and patient selection for patients with tricuspid regurgitation (TR) prior to ITVR.
The Agriculture and Society in the Yiluo River Basin: Archaeobotanical Evidence From the Suyang Site
Authors: Yang Fan , Duan Qimeng , Cheng Baozeng , Ren Guang , Jia Yin , Jin Guiyun
Published: July 2022

The Yiluo River Basin is located in the Central plains of China, an area commonly known as the center of origin of ancient Chinese civilization. Agriculture lays the foundation for social and economic development and triggers societal change and archaeobotany can provide important clues on this issue. archaeobotanical study is an important perspective on the relationship between agriculture and society development. However, relatively few archaeobotanical studies have been conducted in the Yiluo River basin, and the paucity of data has hindered our understanding of the relationship between agriculture and society. Therefore, the archaeobotanical analysis at the Suyang site in the middle reach of the Luo River provides an opportunity to understand how and why agriculture and society developed. Our analytical results of carbonized plant remains and phytolith, coupled with radiocarbon dating, showed that millet was the main crop in the late Yangshao culture (5,500–5000 BP), followed by rice. However, rice cultivation in the area expanded during the Longshan culture (5,000–4000 BP), and its importance as a crop possibly exceeded millet at Suyang. From the late Yangshao to Longshan, rice was cultivated in wet fields by utilizing the Luo River floodplain on a large scale. The proportion of rice at Suyang is the highest among contemporary sites in the Central Plains. It may be related to many reasons such as suitable environmental and geomorphological conditions, advanced water management, the influence of the Qujialing culture, and population growth. In the late Yangshao culture, crop processing seemed to have been concentrated in communal areas. However, during the Longshan culture, different steps of crop processing were scattered throughout the site. This change is hypothesized as a change in the family structure and economic production. After the Yangshao period, the nuclear family became the fundamental unit for social, cultural, and economic production in the Central Plains.
Stratigraphic-Tectonic Evolution and Characterization of the Carboniferous in the Karamay–Baikouquan Fault Zone in the Northwestern Margin of the Junggar Basin, Northwest China
Authors: Ma Yinshan , Wang Tao , Yang Yazhou , Liu Zhiwei , Zhang Lei , Bai Yu
Published: July 2022

The northwestern margin of the Junggar Basin has a complex tectonic history, which is challenging for hydrocarbon exploration. This study highlights the structural patterns, tectonic evolution, and controlling factors of the Karamay–Baikouquan Fault Zone (KBFZ) in the northwestern margin of the Junggar Basin based on well-log and 3D seismic data. The main findings of this study include the following: spatially, we have divided the structural patterns of KBFZ into three zones on the plane, namely, northern, central, and southern zones; temporarily, the tectonic evolution has been divided into five stages from Late Carboniferous to Cretaceous, namely, Early-Middle Carboniferous, Late Carboniferous-Early Permian, Middle-Late Permian, Triassic-Middle Jurassic, and Late Jurassic-Cretaceous. During the Hercynian and Indochina orogeny, the compressional stress from the movement of the Dalabute strike-slip fault and the Genghis–Junggar strike-slip fault produced various degrees of deformation in different locations in the KBFZ. The general structural style is a mixture of strike-slip and thrust-nappe. The main controlling factors include stress period, stress direction, and stratigraphic-lithologic associations. This study has implications for hydrocarbon exploration and development in the northwestern margin of the Junggar Basin.
Volcanic and Seismic Source Modeling: An Open Tool for Geodetic Data Modeling
Authors: Trasatti Elisa
Published: July 2022

Volcanic and Seismic source Modeling (VSM) is an open-source Python tool to model ground deformation. VSM allows the user to choose one or more deformation sources of various shapes as a forward model among sphere, spheroid, ellipsoid, rectangular dislocation, and sill. It supports multiple datasets from most satellite and terrestrial geodetic techniques: Interferometric SAR, GNSS, leveling, Electronic Distance Measurements, tiltmeters, and strainmeters. Two sampling algorithms are available: one is a global optimization algorithm based on the Voronoi cells and yields the best-fitting solution and the second follows a probabilistic approach to parameters estimation based on the Bayes theorem and the Markov chain Monte Carlo method. VSM can be executed as Python script, in Jupyter Notebook environments, or by its Graphical User Interface. Its broad applications range from high-level research to teaching, from single studies to near real-time hazard estimates. Potential users range from early-career scientists to experts. It is freely available on GitHub (https://github.com/EliTras/VSM) and is accompanied by step-by-step documentation in Jupyter Notebooks. This study presents the functionalities of VSM and test cases to describe its use and comparisons among possible settings.
Bottom Drag Variations Under Waves and Currents: A Case Study on a Muddy Deposit off the Shandong Peninsula
Authors: Qi Fukang , Liu Zhiqiang , Xu Jingping
Published: July 2022

Bottom drag coefficient is one of the key parameters in quantifying shelf hydrodynamics and sediment transport processes. It varies markedly due to dynamic forcing and bed type differences, so a set of empirical values have been used for beds of coarse material where bedforms are often present. In comparison, dramatically fewer such rule-of-thumb values are available for muddy beds. Here, we present results of variations in bottom drag as calculated from in situ measurements by bottom-mounted tripods that were placed across the top of a muddy deposit during two different deployments, one in summer and another in winter. A tidal asymmetry of bottom drag was observed, most likely caused by variations of local bed roughness. For hydrodynamically smooth (Re<2.3×105) flows, computed values of bottom drag coefficient were fairly scattered but still showed an overall decreasing trend with an increase in Reynolds number. The bottom drag coefficient for hydrodynamically rough or transitional flow was typically constant, while the averaged drag coefficient over all observation periods was 1.7×10−3. Smaller waves (bottom orbital velocity ub <0.1 m/s) had a very limited impact on the bottom drag coefficient. However, with an increase in ub, the wave–current interactions can decrease the time-averaged near-bed velocity and enhance turbulent kinetic energy, thus leading to an increase in the drag coefficient.
Investigation on Compressibility and Microstructure Evolution of Intact Loess at Different Wetting States
Authors: Jian Tao , Kong Lingwei , Bai Wei , Sun Zhiliang
Published: July 2022

Loess is widely deposited in arid and semi-arid areas and is characterized by low dry density, developed pore space, and loose structure, which is not commensurate with high structural strength and shear strength in the dry state. Many natural phenomena and experimental results show that intact loess is very sensitive to the change of water content, and a slight increase in water content can cause a rapid reduction in strength. Abundant information is available in the literature for the collapsibility of loess. However, research on the evolution of loess compressibility during wetting, which is very helpful in understanding loess collapsible deformation caused by long-term irrigation, remains minimal. To this end, in this article, the evolution of the compressibility of intact loess at different wetting stages is investigated by oedometer tests, and microstructure and pore size distribution (PSD) were characterized on intact loess specimens at different water contents before and after oedometer tests by scanning electron microscope (SEM) and mercury intrusion porosimetry (MIP) methods. The results show that the compression index (Cc) and secondary compression index (Cα) of intact loess depend on water content and vertical stress and change abruptly when vertical stress exceeds yield stress. Cα/Cc values of intact loess are not constant, which increases with vertical stress to a peak and then gradually decreases to 0.025. Wetting and loading can cause damage to the microstructure of intact loess; specifically, loading leads to the collapse of the overhead structure and the transformation from a bimodal PSD into a unimodal PSD, and wetting intensifies the collapse of the microstructure to form a compacted interlocking structure and promotes the transformation of medium pores into small pores.
Perspective: Successes and Challenges in Developing a New Biomolecular Modeling and Design Summer High School Research Internship
Authors: Vater Ashley , Caster Ryan , Haddox Hugh , Olshefsky Audrey , Said Meerit , King Neil P. , Siegel Justin B.
Published: July 2022

In response to the limited research experiences for young scholars during the COVID-19 pandemic and community interest, we developed the Pre-College Rosetta Internship Opportunity (PCR-IO). The mission of PCR-IO was to offer a program to increase equitable access to computational biomolecular research. The PCR-IO program engaged rising senior high school students in a protein therapeutic design project in which they produced novel structural models using the PyRosetta and Foldit software packages. The program comprised a year-long series of activities, with an immersive summer internship that involved students in research as the cornerstone. These activities aimed to support the overarching goal of the program by expanding participating students’ social capital and technical skills, making them more likely to consider and succeed in STEM in their future endeavors. Here we describe the program’s components and rollout and discuss successes and challenges in implementing a remote computational research-based educational high school program. We observed considerable student skill development and conclude that the program created real added value to student participants’ education. We also uncovered issues associated with curriculum pace and found that the required mentorship effort exceeded our expectations. This perspective is intended to offer insight, share recommendations, and create dialog to increase propagation of research-based computational internships, and to shed light on how much novice students can accomplish with mentorship, structured curricula, and access to the research community.
Pan-phylum In Silico Analyses of Nematode Endocannabinoid Signalling Systems Highlight Novel Opportunities for Parasite Drug Target Discovery
Authors: Crooks Bethany A. , Mckenzie Darrin , Cadd Luke C. , McCoy Ciaran J. , McVeigh Paul , Marks Nikki J. , Maule Aaron G. , Mousley Angela , Atkinson Louise E.
Published: July 2022

The endocannabinoid signalling (ECS) system is a complex lipid signalling pathway that modulates diverse physiological processes in both vertebrate and invertebrate systems. In nematodes, knowledge of endocannabinoid (EC) biology is derived primarily from the free-living model species Caenorhabditis elegans, where ECS has been linked to key aspects of nematode biology. The conservation and complexity of nematode ECS beyond C. elegans is largely uncharacterised, undermining the understanding of ECS biology in nematodes including species with key importance to human, veterinary and plant health. In this study we exploited publicly available omics datasets, in silico bioinformatics and phylogenetic analyses to examine the presence, conservation and life stage expression profiles of EC-effectors across phylum Nematoda. Our data demonstrate that: (i) ECS is broadly conserved across phylum Nematoda, including in therapeutically and agriculturally relevant species; (ii) EC-effectors appear to display clade and lifestyle-specific conservation patterns; (iii) filarial species possess a reduced EC-effector complement; (iv) there are key differences between nematode and vertebrate EC-effectors; (v) life stage-, tissue- and sex-specific EC-effector expression profiles suggest a role for ECS in therapeutically relevant parasitic nematodes. To our knowledge, this study represents the most comprehensive characterisation of ECS pathways in phylum Nematoda and inform our understanding of nematode ECS complexity. Fundamental knowledge of nematode ECS systems will seed follow-on functional studies in key nematode parasites to underpin novel drug target discovery efforts.
Advanced Engineering Materials for Enhancing Thermal Management and Thermal Safety of Lithium-Ion Batteries: A Review
Authors: Yang Shichun , Lin Jiayuan , Zhang Zhengjie , Zhang Cheng , Zheng Xu , Xie Wentao , Wang Lijing , Chen Siyan , Liu Xinhua
Published: July 2022

Lithium-ion batteries (LiBs) are the key power source for electric vehicles (EVs). Battery thermal management system (BTMS) is essential to ensure safety and extend service life of LIBs. This paper reviews the various refrigeration materials used in the BTMS in EVs, including liquid coolant, phase change material (PCM). The thermal properties of these refrigerant materials are summarized and the innovative ways to improve the cooling efficiency of the BTMS are analyzed. The various ways to enhance the battery’s thermal performance by modifying the materials of the electrode, separator, and electrolyte are also reviewed. Finally, the research prospect in area of BTMS is summarized. This review will inspire new BTMS design and further improvement in battery safety and performance with the aid of advanced intelligent technologies.
Growth in the Economic and Hydraulic Engineering Capacities Drives Water Quality Improvement in the Eastern Region of Nansi Lake, China
Authors: Zhao Yuhang , Wu Shiqiang , Dai Jiangyu , Wu Xiufeng , Zhang Yu , Yang Rui , Wu Chenhui , Feng Kedong
Published: July 2022

Knowledge of the extent of water pollution along a diversion channel is essential for ensuring the security and effectiveness of water diversion projects. Thus, identifying the trends in the water quality and the factors which influence the trends along a diverted river is a prerequisite to ensuring the safety of the water diversion. As an important control unit of the Eastern Route of the South to North Water Diversion Project, the hilly eastern region of Nansi Lake Basin (ENLB) suffers excess water pollution in the water transferred into Nansi Lake during the flood season. The comprehensive pollution index (CPI), the Mann-Kendall trend test and analysis of variances were used to characterize the spatiotemporal variation of water quality in the three main mountainous rivers of the ENLB. The contribution of different factors which influencing the variation of the water quality parameters may be explained using ridge regression analysis. The results showed that the CPI for the three major rivers decreased significantly from 2000 to 2012. The rivers had problems in compliance, and this was most noticeable in the Guangfu River. The main pollutants exceeding the water quality standards were the chemical oxygen demand and total phosphorus. The GDP per capita was the largest factor which influenced the changes in the regional water quality, with the average contribution being 30%. An increase in the water storage capacity was shown to have a positive effect on improving the water quality. The results provided a scientific basis for establishing a regional pollution control strategy and would give support to the planning of future water diversion projects.
Nitrogen Fertilization of Lawns Enhanced Soil Nitrous Oxide Emissions by Increasing Autotrophic Nitrification
Authors: Xun Zhifeng , Xu Tianyue , Ren Baihui , Zhao Xinghan , Quan Zhi , Bai Long , Fang Yunting
Published: July 2022

As nitrous oxide (N2O) is one of the most important greenhouse gases, N2O emission pathways and regulation techniques in soils with different vegetation types have become a research focus. Currently, a diverse array of research exists on the N2O emissions from soils of different vegetation types, e.g., forest, grassland, and agriculture. Few studies have investigated the microbial processes of N2O emissions from lawn soils. Fertilization levels in lawn soils are often similar to or much higher than those in agricultural ecosystems, thus fertilized lawn is an important source of atmospheric N2O. In the study, we employed the 15N-nitrate labelling method combined with the nitrification inhibition technique to distinguish microbial processes and their contribution to N2O emissions in long-term nitrogen fertilised lawns. We found that the N2O emission rate from the control treatment was 1.0 nmol g−1 h−1 over the incubation, with autotrophic nitrification contributing 60%. The N2O emission rate increased to 1.4 nmol g−1 h−1 from the soil treated with long-term N fertilization, and the contribution of autotrophic nitrification increased to 69%. N fertilization did not significantly increase the contribution of denitrification (24–26%) in the total N2O emissions. However, N fertilization substantially decreased the contribution of heterotrophic nitrification from 13 to 0.4% in the total N2O emissions. Co-denitrification to N2O was detected but the overall contribution was of minor importance (3–5%). The correlation analysis revealed that soil NO3− levels were the main influencing factors in the N2O producing microbial processes. Our results suggest that N fertilization altered both N2O production rates and the contribution pattern of microbial processes, and indicate the autotrophic nitrification and heterotrophic nitrification are more sensitive to N fertilization than denitrification and co-denitrification.
Would the Urban Environmental Legislation Realize the Porter Hypothesis? Empirical Evidence Based on Panel Data of Chinese Prefecture Cities
Authors: Zhang Fan , Yang Yiwu , Ahmad Mahmood , Shao Junjie
Published: July 2022

The Porter hypothesis suggests that well-designed environmental regulation can trigger regional technological innovation that helps gain competitiveness. Little attention has been paid to whether China’s urban environmental legislation supports Porter hypothesis (PH). An empirical test was conducted based on panel data of 218 prefecture-level cities during 2003–2017 to examine the effects of urban environmental legislation on innovation and green total factor productivity (green TFP). The findings reveal that the urban environmental legislation increased the number of local green patents, which means that the weak Porter hypothesis was established. However, the urban environmental legislation did not lead to an increase in green TFP so that the strong version of PH did not hold. Further analysis showed that the urban environmental legislation led to the decline of green TFP and the increase of green patents in the west of China, but in the east and central cities, the changes were not visible. Besides, the legislation did not promote green TFP improvement through green innovation in the short term, which means it did not realize process compensation.
Food Restriction Reveals Individual Differences in Insulin-Like Growth Factor-1 Reaction Norms
Authors: Tóth Zsófia , Mahr Katharina , Ölveczki Gyula , Őri Levente , Lendvai Ádám Zoltán
Published: July 2022

Most organisms have to cope with unpredictable environmental challenges such as fluctuations in nutritional resources. Insulin-like growth factor-1 (IGF-1) is an evolutionarily conserved hormone that is highly sensitive to the individual nutritional status and regulates major life-history traits including lifespan and reproduction across vertebrates. We investigated the role of IGF-1 during periods of food shortages by altering between two feeding regimes (110 and 70% of daily food intake) after a period ofad libitumfeeding in captive bearded reedlings (Panurus biarmicus). Each dietary treatment was repeated twice. Birds lost mass under food restriction, but the magnitude of mass change depended on the preceding dietary conditions. Moreover, bearded reedlings showed large, repeatable individual differences in their IGF-1 reaction norms with some individuals increasing IGF-1 levels in response to a restricted diet, whereas others showed no responses or decreased IGF-1 levels. This variation was explained by differences in average body mass: heavier individuals had higher IGF-1 levels during the control treatment and were more likely to decrease IGF-1 levels in response to the dietary restriction than did lighter ones. This result uncovers an individual by environment interaction (I × E) and may have important implications for the evolution of IGF-1 related hormonal phenotypes in this species.
Spatiotemporal Variations of Human Pressure on Key Biodiversity Areas in the Qinghai–Tibet Plateau: A Comparative Analysis
Authors: Zeng Yuxi , Wang Ling-en , Zhong Linsheng
Published: July 2022

A key biodiversity area (KBA) is one of the important emerging area-based conservation measures that is being implemented recently in China; however, the human pressure faced by a KBA is still unclear. This study analyzed the spatiotemporal variation of human pressure on KBAs from 1990 to 2017 and compared it with the human pressure on national natural reserves (NNRs) through a case study of the Qinghai–Tibet Plateau. In addition, changes in the trend of human pressure before and after 2010 were analyzed to examine the influence of conservation policies on human pressure. Results showed that human pressure on KBAs and NNRs gradually increased from 1990 to 2017. Furthermore, the growth rates and mean values of human pressure in KBAs were higher than those in NNRs. After the implementation of conservation policies in 2010, the growth rates of human pressure on both KBAs and NNRs have significantly slowed, and the areas with negative growth in both KBAs and NNRs have gradually expanded. In addition to providing an understanding of the changing spatiotemporal trends of human pressure on KBAs, this study can serve as a reference to formulate policies for the improvement of the effectiveness of conservation.
Provenance Differences in Water-Use Efficiency Among Sessile Oak Populations Grown in a Mesic Common Garden
Authors: Rabarijaona Arivoara , Ponton Stéphane , Bert Didier , Ducousso Alexis , Richard Béatrice , Levillain Joseph , Brendel Oliver
Published: July 2022

Context

As a widespread species, sessile oak (Quercus petraea) populations occupy a wide range of ecological conditions, with large gradients of soil water availability. Drought acclimation involves a plastic increase in water-use efficiency (WUE), a trait that is easily measured using the carbon isotope composition (δ13C). However, the question remains whether WUE is an adaptive trait that impacts the fitness of trees in natural environments.

Objectives and Methods

To investigate whether WUE was a drought-adaptive trait, we studied a sample of 600 trees originating from 16 provenances, grown for 21 years in a common garden. Intrinsic WUE (WUEi), estimated from tree ring δ13C, was compared among and within populations for three climatically contrasted years. The adaptive character of WUEi was evaluated by relating population mean WUEi, as well as its plasticity to drought, to the pedoclimatic conditions of their provenance sites. The contribution of WUEi to tree and population fitness was finally assessed from the relationship between WUEi and tree radial growth (GI).

Results

Significant differences in WUEi were found among populations but a much larger variability was observed within than among populations. The population WUEi of the juvenile oak trees growing in the relatively mesic conditions of the common garden showed no relationship with a modeled water deficit index for the provenance sites. However, a higher population WUEi plasticity to severe drought was related to a higher proportion of silt and carbon and a lower proportion of sand in the soil of the provenance sites. In response to severe drought, populations with a higher increase in WUEi showed a lower decrease in GI. Populations with lower GI reduction were from sites with higher vapor pressure deficit in May–July (VPD). For the wet year only, populations with a higher WUEi also had a higher GI.

Conclusion

The correlations observed at the common garden site between (i) population means of WUEi plasticity to drought and soil texture of the provenance sites, and (ii) GI plasticity to drought and VPD, suggested a local adaptation of sessile oak.
Antimicrobial Effect of Extracellular Vesicles Derived From Human Oral Mucosal Epithelial Cells on Candida albicans
Authors: Zhao Maomao , Zhang Miaomiao , Xu Kaiyuan , Wu Kaihui , Xie Ruiqi , Li Ruowei , Wang Qiong , Liu Weida , Wang Wenmei , Wang Xiang
Published: July 2022

Candida albicans (C. albicans) is a commensal microorganism that colonizes the mucosal surfaces of healthy individuals. Changes in the host or environment can lead to overgrowth of C. albicans and infection of the host. Extracellular vesicles (EVs) are released by almost all cell types and play an increasingly recognized role in fighting microbial infection. The aim of the present study was to assess whether EVs derived from human oral mucosal epithelial (Leuk-1) cells can suppress the growth and invasion of C. albicans. The in vitro efficacy of Leuk-1-EVs against C. albicans was assessed by optical microscopy, laser scanning confocal microscopy, scanning electron microscopy, and transmission electron microscopy. The germ tube formation rate, the percentage of hyphae and the microcolony optical density were also used to analyze the growth of C. albicans in a coculture model with Leuk-1 cells and EVs or after inhibition of the secretion of EVs. A mouse model of oral candidiasis was established and submucosal injection of Leuk-1-EVs in the tongue was performed. Macroscopic observation, H&E staining, PAS staining, and scanning electron microscopy were used to assess antifungal effects of Leuk-1-EVs in vivo. The in vitro results showed that the growth of C. albicans was inhibited and that the morphology and ultrastructure were changed following Leuk-1-EVs treatment. The in vivo results exhibited that white lesions of the tongue, C. albicans infection, and oral mucosal inflammation of the infected mice were significantly alleviated after Leuk-1-EVs treatment. We thus reveal an antifungal capability of EVs derived from oral epithelial cells against C. albicans that is mediated by direct damage effects and potential synergy between EVs and human oral mucosal epithelial cells. This finding offers an intriguing, previously overlooked method of antifungal defense against C. albicans.
Recruited and Tissue-Resident Natural Killer Cells in the Lung During Infection and Cancer
Authors: Franklin Miriam , Connolly Emma , Hussell Tracy
Published: July 2022

Natural killer (NK) cells are an important component of the innate immune system, and have a key role in host defense against infection and in tumor surveillance. Tumors and viruses employ remarkably similar strategies to avoid recognition and killing by NK cells and so much can be learnt by comparing NK cells in these disparate diseases. The lung is a unique tissue environment and immune cells in this organ, including NK cells, exist in a hypofunctional state to prevent activation against innocuous stimuli. Upon infection, rapid NK cell infiltration into the lung occurs, the amplitude of which is determined by the extent of inflammation and damage. Activated NK cells kill infected cells and produce pro-inflammatory cytokines and chemokines to recruit cells of the adaptive immune system. More recent evidence has shown that NK cells also play an additional role in resolution of inflammation. In lung cancer however, NK cell recruitment is impaired and those that are present have reduced functionality. The majority of lung NK cells are circulatory, however recently a small population of tissue-resident lung NK cells has been described. The specific role of this subset is yet to be determined, but they show similarity to resident memory T cell subsets. Whether resident or recruited, NK cells are important in the control of pulmonary infections, but equally, can drive excessive inflammation if not regulated. In this review we discuss how NK cells are recruited, controlled and retained in the specific environment of the lung in health and disease. Understanding these mechanisms in the context of infection may provide opportunities to promote NK cell recruitment and function in the lung tumor setting.
The Neutrophil-to-Lymphocyte and Monocyte-to-Lymphocyte Ratios Are Independently Associated With the Severity of Autoimmune Encephalitis
Authors: Liu Zhiwei , Li Yimeng , Wang Yaoyao , Zhang Haifeng , Lian Yajun , Cheng Xuan
Published: July 2022

Background

The neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) are biomarkers that may reflect inflammatory status in some immune-related diseases. This study aims to investigate the association of NLR and MLR with the severity and prognosis of autoimmune encephalitis (AE).

Methods

A total of 199 patients diagnosed with AE in the First Affiliated Hospital of Zhengzhou University from October 2015 to October 2021 were retrospectively analyzed. The Clinical Assessment Scale for Autoimmune Encephalitis (CASE) and the modified Rankin Scale (mRS) were used to evaluate the severity of the patients at admission, and the patients were divided into mild group (CASE ≤ 4) and severe group (CASE ≥ 5) according to the CASE score. Poor prognosis was described as an mRS of 3 or more at 12 months. Binary logistic regression analysis was performed to assess risk factors for the severity and prognosis of AE.

Results

NLR and MLR of severe group were significantly higher than that of mild group. NLR and MLR were positively correlated with the CASE score (r = 0.659, P < 0.001; r = 0.533, P < 0.001) and the mRS score (r = 0.609, P < 0.001;r = 0.478, P < 0.001) in AE patients. Multivariate logistic analysis showed that NLR (OR = 1.475, 95%CI: 1.211-1.796, P < 0.001) and MLR (OR = 15.228, 95%CI: 1.654-140.232, P = 0.016) were independent risk factors for the severity of AE. In addition, the CASE score and the mRS score were positively correlated (r = 0.849, P < 0.001). Multivariate logistic analysis showed that the CASE at admission (OR = 1.133, 95%CI: 1.043-1.229, P = 0.003) and age (OR = 1.105, 95%CI: 1.062-1.150, P < 0.001) were independent risk factors for the poor prognosis of AE patients. The NLR and MLR at admission and whether they decreased after immunotherapy were not associated with the prognosis of AE patients (P > 0.05).

Conclusions

NLR and MLR, readily available and widespread inflammatory markers, were helpful for clinicians to monitor disease progression and identify potentially severe patients of AE early to optimize clinical treatment decisions.
Unveiling Leukocyte Extracellular Traps in Inflammatory Responses of the Central Nervous System
Authors: Colciaghi Francesca , Costanza Massimo
Published: July 2022

Over the past nearly two decades, increasing evidence has uncovered how immune cells can actively extrude genetic material to entrap invading pathogens or convey sterile inflammatory signals that contribute to shaping immune responses. Originally identified in neutrophils, the release of decondensed chromatin fibers decorated with antimicrobial proteins, called extracellular traps (ETs), has been recognized as a specific form of programmed inflammatory cell death, which is now known to occur in several other leukocytes. Subsequent reports have shown that self-DNA can be extruded from immune cells even in the absence of cell death phenomena. More recent data suggest that ETs formation could exacerbate neuroinflammation in several disorders of the central nervous system (CNS). This review article provides an overview of the varied types, sources, and potential functions of extracellular DNA released by immune cells. Key evidence suggesting the involvement of ETs in neurodegenerative, traumatic, autoimmune, and oncological disorders of the CNS will be discussed, outlining ongoing challenges and drawing potentially novel lines of investigation.
A Path-Based Analysis of Infected Cell Line and COVID-19 Patient Transcriptome Reveals Novel Potential Targets and Drugs Against SARS-CoV-2
Authors: Agrawal Piyush , Sambaturu Narmada , Olgun Gulden , Hannenhalli Sridhar
Published: July 2022

Most transcriptomic studies of SARS-CoV-2 infection have focused on differentially expressed genes, which do not necessarily reveal the genes mediating the transcriptomic changes. In contrast, exploiting curated biological network, our PathExt tool identifies central genes from the differentially active paths mediating global transcriptomic response. Here we apply PathExt to multiple cell line infection models of SARS-CoV-2 and other viruses, as well as to COVID-19 patient-derived PBMCs. The central genes mediating SARS-CoV-2 response in cell lines were uniquely enriched for ATP metabolic process, G1/S transition, leukocyte activation and migration. In contrast, PBMC response reveals dysregulated cell-cycle processes. In PBMC, the most frequently central genes are associated with COVID-19 severity. Importantly, relative to differential genes, PathExt-identified genes show greater concordance with several benchmark anti-COVID-19 target gene sets. We propose six novel anti-SARS-CoV-2 targets ADCY2, ADSL, OCRL, TIAM1, PBK, and BUB1, and potential drugs targeting these genes, such as Bemcentinib, Phthalocyanine, and Conivaptan.
Two Main Cellular Components in Rheumatoid Arthritis: Communication Between T Cells and Fibroblast-Like Synoviocytes in the Joint Synovium
Authors: Tu Jiajie , Huang Wei , Zhang Weiwei , Mei Jiawei , Zhu Chen
Published: July 2022

Rheumatoid arthritis (RA) is a chronic autoimmune disease that endangers the health of approximately 1% of the global population. Current RA medications on the market mainly include non-steroidal anti-inflammatory drugs, biological agents, and disease-modifying drugs. These drugs aim to inhibit the overactivated immune response or inflammation of RA, but they cannot cure RA. A better understanding of the pathogenesis of RA will provide a new understanding to search for RA targets and for drug development. The infiltration of T cells and hyper-proliferation of fibroblast-like synoviocytes (FLS) in the synovium of patients with RA are significantly upregulated. Furthermore, the abnormal activation of these two types of cells has been confirmed to promote development of the course of A by many studies. This article systematically summarizes the interactions between T cells and FLS in RA synovial tissues, including one-way/mutual regulation and direct/indirect regulation between the two. It further aims to investigate the pathogenesis of RA from the perspective of mutual regulation between T cells and FLS and to provide new insights into RA research.
Inside-Out of Complement in Cancer
Authors: Kolev Martin , Das Madhumita , Gerber Monica , Baver Scott , Deschatelets Pascal , Markiewski Maciej M.
Published: July 2022

The role of complement in cancer has received increasing attention over the last decade. Recent studies provide compelling evidence that complement accelerates cancer progression. Despite the pivotal role of complement in fighting microbes, complement seems to suppress antitumor immunityviaregulation of host cell in the tumor microenvironment. Although most studies link complement in cancer to complement activation in the extracellular space, the discovery of intracellular activation of complement, raises the question: what is the relevance of this process for malignancy? Intracellular activation is pivotal for the survival of immune cells. Therefore, complement can be important for tumor cell survival and growth regardless of the role in immunosuppression. On the other hand, because intracellular complement (the complosome) is indispensable for activation of T cells, these functions will be essential for priming antitumor T cell responses. Here, we review functions of complement in cancer with the consideration of extra and intracellular pathways of complement activation and spatial distribution of complement proteins in tumors and periphery and provide our take on potential significance of complement as biomarker and target for cancer therapy.
TIGIT Deficiency Protects Mice From DSS-Induced Colitis by Regulating IL-17A–Producing CD4+ Tissue-Resident Memory T Cells
Authors: Chen Binfeng , Ye Baokui , Li Mengyuan , Wang Shuyi , Li Jin , Lai Yimei , Yang Niansheng , Ke Zunfu , Zhang Hui
Published: July 2022

Tissue-resident memory T cells (TRM cells) have been shown to play an instrumental role in providing local immune responses for pathogen clearance in barrier tissues. However, their contribution to inflammatory bowel diseases (IBDs) and the underlying regulation are less clear. Here, we identified a critical role of T-cell immunoreceptor with immunoglobulin and ITIM (TIGIT) in regulating CD4+ TRM cells in an experimental model of intestinal inflammation. We found that CD4+ TRM cells were increased and correlated with disease activities in mice with dextran sulfate sodium (DSS)-induced colitis. Phenotypically, these CD4+ TRM cells could be classified into CD69+CD103− and CD69+CD103+ subsets. Functionally, these CD4+ TRM cells were heterogeneous. CD69+CD103− CD4+ TRM cells were pro-inflammatory and produced interferon-γ (IFNγ) and interleukin-17A (IL-17A), which accounted for 68.7% and 62.9% of total IFNγ+ and IL-17A+ CD4+ T cells, respectively, whereas CD69+CD103+ CD4+ TRM cells accounted for 73.7% Foxp3+ regulatory T cells. TIGIT expression was increased in CD4+ T cells in the gut of mice with DSS-induced colitis. TIGIT deficiency impaired IL-17A expression in CD69+CD103− CD4+ TRM cells specifically, resulting in ameliorated gut inflammation and tissue injury. Together, this study provides new insights into the regulation of gut inflammation that TIGIT deficiency protects mice from DSS-induced colitis, which might have a potential therapeutic value in the treatment of IBDs.
African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING
Authors: Zheng Wanglong , Xia Nengwen , Zhang Jiajia , Cao Qi , Jiang Sen , Luo Jia , Wang Hui , Chen Nanhua , Zhang Quan , Meurens François , Zhu Jianzhong
Published: July 2022

African swine fever virus (ASFV) encodes more than 150 proteins, which establish complex interactions with the host for the benefit of the virus in order to evade the host’s defenses. However, currently, there is still a lack of information regarding the roles of the viral proteins in host cells. Here, our data demonstrated that ASFV structural protein p17 exerts a negative regulatory effect on cGAS-STING signaling pathway and the STING signaling dependent anti-HSV1 and anti-VSV functions. Further, the results indicated that ASFV p17 was located in ER and Golgi apparatus, and interacted with STING. ASFV p17 could interfere the STING to recruit TBK1 and IKKϵ through its interaction with STING. It was also suggested that the transmembrane domain (amino acids 39–59) of p17 is required for interacting with STING and inhibiting cGAS-STING pathway. Additionally, with the p17 specific siRNA, the ASFV induced IFN-β, ISG15, ISG56, IL-6 and IL-8 gene transcriptions were upregulated in ASFV infected primary porcine alveolar macrophages (PAMs). Taken together, ASFV p17 can inhibit the cGAS-STING pathway through its interaction with STING and interference of the recruitment of TBK1 and IKKϵ. Our work establishes the role of p17 in the immune evasion and thus provides insights on ASFV pathogenesis.
SARS-CoV-2 Achieves Immune Escape by Destroying Mitochondrial Quality: Comprehensive Analysis of the Cellular Landscapes of Lung and Blood Specimens From Patients With COVID-19
Authors: Duan Chenyang , Ma Ruiyan , Zeng Xue , Chen Bing , Hou Dongyao , Liu Ruixue , Li Xuehan , Liu Liangming , Li Tao , Huang He
Published: July 2022

Mitochondria get caught in the crossfire of coronavirus disease 2019 (COVID-19) and antiviral immunity. The mitochondria-mediated antiviral immunity represents the host’s first line of defense against viral infection, and the mitochondria are important targets of COVID-19. However, the specific manifestations of mitochondrial damage in patients with COVID-19 have not been systematically clarified. This study comprehensively analyzed one single-cell RNA-sequencing dataset of lung tissue and two bulk RNA-sequencing datasets of blood from COVID-19 patients. We found significant changes in mitochondrion-related gene expression, mitochondrial functions, and related metabolic pathways in patients with COVID-19. SARS-CoV-2 first infected the host alveolar epithelial cells, which may have induced excessive mitochondrial fission, inhibited mitochondrial degradation, and destroyed the mitochondrial calcium uniporter (MCU). The type II alveolar epithelial cell count decreased and the transformation from type II to type I alveolar epithelial cells was blocked, which exacerbated viral immune escape and replication in COVID-19 patients. Subsequently, alveolar macrophages phagocytized the infected alveolar epithelial cells, which decreased mitochondrial respiratory capacity and activated the ROS–HIF1A pathway in macrophages, thereby aggravating the pro-inflammatory reaction in the lungs. Infected macrophages released large amounts of interferon into the blood, activating mitochondrial IFI27 expression and destroying energy metabolism in immune cells. The plasma differentiation of B cells and lung-blood interaction of regulatory T cells (Tregs) was exacerbated, resulting in a cytokine storm and excessive inflammation. Thus, our findings systematically explain immune escape and excessive inflammation seen during COVID-19 from the perspective of mitochondrial quality imbalance.