bluuebunny/crossref_metadata_2025 huggingface dataset:
INFLUENCE OF LONG-TERM APPLICATION OF FERTILIZERS ON BOTANICAL COMPOSITION OF HAYFIELD PHYTOCENOSIS AND THE QUALITY OF THE RECEIVED FODDER
Authors: Teberdiev Dalhat , Rodionova Anna , Zapivalov Sergey , Shchannikova Maria
Published: July 2021

In the Federal Williams Research Center of Forage Production and Agroecology in 1947 the study of the effectiveness of mineral and organic fertilizers was started. For 74 years of using the herbage without re-sowing, the features of succession variability have been revealed. There was a reformation of the seeded legume-grass herbage into two types: low grass-legume-motley grass against the background of the use of one- and two-component mineral fertilizers and manure (regressive succession) and grass-motley grass with the application of complete mineral fertilizer with high doses of nitrogen (progressive succession). On the herbage of the first type, the predominant species is the introduced species — red fescue (43.8–75.4%), on the herbage of the second type — high grasses (meadow foxtail, cocksfoot, awnless brome). The reformation of the herbage did not lead to a decrease in yield. Over the past 28 years (average for 1993–2020), the yield of herbage with regressive succession exceeded the control (3.3 t/ha dry matter) by 1.1–1.9 times, with progressive succession by 1.9–2.6 times. The annual consumption of nitrogen by grasses in the control was 54 kg, P2O5 — 14 kg, K2O — 46 kg. The application of one- and two-component mineral fertilizer and manure increases the consumption of nitrogen by 1.1–2.4 times, phos-phorus — by 1.3–3.1 times, potassium — by 1.3–3.6 times, the application of complete mineral fertilizer, respectively, in 2.3–3.5, 2.9–3.9 and 2.4–3.9 times. The quality of the received feed for the content of crude protein, crude fiber and crude ash on both types of herbage met the requirements of standard for the first and second class. The content of mineral elements also met the zootechnical standards.
The Effect of Step Width on Muscle Contributions to Body Mass Center Acceleration During the First Stance of Sprinting
Authors: Wang Ruoli , Martín de Azcárate Laura , Sandamas Paul , Arndt Anton , Gutierrez-Farewik Elena M.
Published: July 2021

Background

At the beginning of a sprint, the acceleration of the body center of mass (COM) is driven mostly forward and vertically in order to move from an initial crouched position to a more forward-leaning position. Individual muscle contributions to COM accelerations have not been previously studied in a sprint with induced acceleration analysis, nor have muscle contributions to the mediolateral COM accelerations received much attention. This study aimed to analyze major lower-limb muscle contributions to the body COM in the three global planes during the first step of a sprint start. We also investigated the influence of step width on muscle contributions in both naturally wide sprint starts (natural trials) and in sprint starts in which the step width was restricted (narrow trials).

Method

Motion data from four competitive sprinters (2 male and 2 female) were collected in their natural sprint style and in trials with a restricted step width. An induced acceleration analysis was performed to study the contribution from eight major lower limb muscles (soleus, gastrocnemius, rectus femoris, vasti, gluteus maximus, gluteus medius, biceps femoris, and adductors) to acceleration of the body COM.

Results

In natural trials, soleus was the main contributor to forward (propulsion) and vertical (support) COM acceleration and the three vasti (vastus intermedius, lateralis and medialis) were the main contributors to medial COM acceleration. In the narrow trials, soleus was still the major contributor to COM propulsion, though its contribution was considerably decreased. Likewise, the three vasti were still the main contributors to support and to medial COM acceleration, though their contribution was lower than in the natural trials. Overall, most muscle contributions to COM acceleration in the sagittal plane were reduced. At the joint level, muscles contributed overall more to COM support than to propulsion in the first step of sprinting. In the narrow trials, reduced COM propulsion and particularly support were observed compared to the natural trials.

Conclusion

The natural wide steps provide a preferable body configuration to propel and support the COM in the sprint starts. No advantage in muscular contributions to support or propel the COM was found in narrower step widths.
Biomechanical Analysis of Cervical Artificial Disc Replacement Using Cervical Subtotal Discectomy Prosthesis
Authors: Wo Jin , Lv Zhenjing , Wang Jing , Shen Kui , Zhu Haoran , Liu Yang , Huang Yuen , Sun Guodong , Li Zhizhong
Published: July 2021

Background: Anterior cervical discectomy and fusion (ACDF) sacrifices segmental mobility, which can lead to the acceleration of adjacent segment degeneration. The challenge has promoted cervical artificial disc replacement (CADR) as a substitute for ACDF. However, CADR has revealed a series of new issues that are not found in ACDF, such as hypermobility, subsidence, and wear phenomenon. This study designed a cervical subtotal discectomy prosthesis (CSDP) consisting of a cervical disc prosthesis structure (CDP structure), cervical vertebra fixation structure (CVF structure), link structure, and locking screw, aiming to facilitate motion control and reduce subsidence. The aim of this study was to assess the biomechanics of the CSDP using finite element (FE) analysis, friction-wear test, and non-human primates implantation study.

Study Design: For the FE analysis, based on an intact FE C2-C7 spinal model, a CSDP was implanted at C5-C6 to establish the CSDP FE model and compare it with the Prestige LP prosthesis (Medtronic Sofamor Danek, Minneapolis, MN, United States). The range of motion (ROM), bone-implant interface stress, and facet joint force were calculated under flexion extension, lateral bending, and axial rotation. In addition, CSDP was elevated 1 mm to mimic an improper implantation technique to analyze the biomechanics of CSDP errors in the FE model. Moreover, the friction-wear test was conducted in vitro to research CSDP durability and observe surface wear morphology and total wear volume. Finally, the CSDP was implanted into non-human primates, and its properties were evaluated and verified by radiology.

Results: In the FE analysis, the ROM of the CSDP FE model was close to that of the intact FE model in the operative and adjacent segments. In the operative segment, the CSDP error FE model increased ROM in flexion extension, lateral bending, and axial rotation. The maximum stress in the CSDP FE model was similar to that of the intact FE model and was located in the peripheral cortical bone region. The facet joint force changes were minimal in extension, lateral bending, and axial rotation loads in CSDP. In the friction-wear test, after the 150-W movement simulation, both the CVF-link-junction and the CDP-link-junction had slight wear. In the CSDP non-human primate implantation study, no subsidence, dislocation, or loosening was observed.

Conclusion: In the FE analysis, the biomechanical parameters of the CSDP FE model were relatively close to those of the intact FE model when compared with the Prestige LP FE model. In terms of CSDP error FE models, we demonstrated that the implantation position influences CSDP performance, such as ROM, bone-implant interface stress, and facet joint force. In addition, we performed a friction-wear test on the CSDP to prove its durability. Finally, CSDP studies with non-human primates have shown that the CSDP is effective.
Enzyme Catalyzed Copolymerization of Lignosulfonates for Hydrophobic Coatings
Authors: Mayr Sebastian A. , Schwaiger Nikolaus , Weber Hedda K. , Kovač Janez , Guebitz Georg M. , Nyanhongo Gibson S.
Published: July 2021

Enzymatic polymerization of lignin can generate a variety of value-added products concomitantly replacing fossil-based resources. In line with this approach, a laccase from the thermophilic fungus Myceliophthora thermophila (MtL) was used to couple a hydrophobicity enhancing fluorophenol (FP) molecule, namely 4-[4-(trifluoromethyl)phenoxy]phenol (4,4-F3MPP), as a model substrate onto lignosulfonate (LS). During the coupling reaction changes in fluorescence, phenol content, viscosity and molecular weight (size exclusion chromatography; SEC) were monitored. The effects of enzymatic coupling of FP onto LS on hydrophobicity were investigated by the means of water contact angle (WCA) measurement and determination of swelling capacity. Full polymerization of LS resulting in the production of water-insoluble polymers was achieved at a pH of 7 and 33°C. Incorporation of 2% (w/v) of FP led to an increase in WCA by 59.2% while the swelling capacity showed a decrease by 216.8%. Further, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis indicated successful covalent coupling of the FP molecule onto LS by an emerging peak at 1,320 cm–1 in the FTIR spectrum and the evidence of Fluor in the XPS spectrum. This study shows the ability of laccase to mediate the tailoring of LS properties to produce functional polymers.
Chondrocyte Aging: The Molecular Determinants and Therapeutic Opportunities
Authors: Ramasamy Thamil Selvee , Yee Yong Mei , Khan Ilyas M.
Published: July 2021

Osteoarthritis (OA) is a joint degenerative disease that is an exceedingly common problem associated with aging. Aging is the principal risk factor for OA, but damage-related physiopathology of articular chondrocytes probably drives the mechanisms of joint degeneration by a progressive decline in the homeostatic and regenerative capacity of cells. Cellular aging is the manifestation of a complex interplay of cellular and molecular pathways underpinned by transcriptional, translational, and epigenetic mechanisms and niche factors, and unraveling this complexity will improve our understanding of underlying molecular changes that affect the ability of the articular cartilage to maintain or regenerate itself. This insight is imperative for developing new cell and drug therapies for OA disease that will target the specific causes of age-related functional decline. This review explores the key age-related changes within articular chondrocytes and discusses the molecular mechanisms that are commonly perturbed as cartilage ages and degenerates. Current efforts and emerging potential therapies in treating OA that are being employed to halt or decelerate the aging processes are also discussed.
Comparison of Genome-Wide DNA Methylation Profiles of Human Fetal Tissues Conceived by in vitro Fertilization and Natural Conception
Authors: Liu Ye , Li Xinzhu , Chen Songchang , Wang Li , Tan Yajing , Li Xiaocui , Tang Lin , Zhang Junyu , Wu Dandan , Wu Yanting , Liu Xinmei , Zhu Yimin , Sheng Jianzhong , Pan Jiexue , Jin Li , Huang Hefeng
Published: July 2021

Background

Assisted reproductive technology (ART) might induce adverse pregnancy outcomes and increase the risk of metabolic diseases in offspring’ later life with unknown reasons. Here we evaluated the global methylation level and methylation profile of fetal tissue from elective terminations of pregnancy (ETP) after natural conception and multifetal pregnancy reduction (MFPR) after in vitro fertilization and embryo transfer (IVF-ET).

Results

Global methylation levels were comparable between the fetal tissue of ETP after natural conception group and MFPR after IVF-ET group. The methylation levels were lower in the hypermethylated regions of the MFPR group than in the ETP group, while the methylation levels were higher in the hypomethylated regions of the MFPR group. Heatmap visualization and hierarchical clustering of the candidate differentially methylated regions (DMRs) showed differences between the DMRs in the ETP and MFPR samples. We identified 196 differentially methylated regions that matched 164 genes between the ETP and MFPR groups. In the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, skeletal system morphogenesis and diabetes mellitus ranked first. Ingenuity Pathway Analysis (IPA) revealed 8 diseases and functional annotations associated with IVT-ET. In the MFPR group, the final validation showed lower methylation levels in gene bodies of bone morphogenetic protein 4 (BMP4), higher methylation levels in the 1st exon and 5′UTR of thyroid peroxidase (TPO), and higher methylation levels in TSS1500 and TSS200 of interleukin 1 beta (IL1B).

Conclusions

ART does not alter global DNA methylation level, but influences DNA methylation variation in specific regions of human fetus in the early stage of life. Further studies are warranted to clarify the potential role of DNA methylation alterations in the gene expression profile.
Nerve Suture Combined With ADSCs Injection Under Real-Time and Dynamic NIR-II Fluorescence Imaging in Peripheral Nerve Regeneration in vivo
Authors: Dong Shixian , Feng Sijia , Chen Yuzhou , Chen Mo , Yang Yimeng , Zhang Jian , Li Huizhu , Li Xiaotong , Ji Liang , Yang Xing , Hao Yuefeng , Chen Jun , Wo Yan
Published: July 2021

Peripheral nerve injury gives rise to devastating conditions including neural dysfunction, unbearable pain and even paralysis. The therapeutic effect of current treatment for peripheral nerve injury is unsatisfactory, resulting in slow nerve regeneration and incomplete recovery of neural function. In this study, nerve suture combined with ADSCs injection was adopted in rat model of sciatic nerve injury. Under real-time visualization of the injected cells with the guidance of NIR-II fluorescence imaging in vivo, a spatio-temporal map displaying cell migration from the proximal injection site (0 day post-injection) of the nerve to the sutured site (7 days post-injection), and then to the distal section (14 days post-injection) was demonstrated. Furthermore, the results of electromyography and mechanical pain threshold indicated nerve regeneration and functional recovery after the combined therapy. Therefore, in the current study, the observed ADSCs migration in vivo, electrophysiological examination results and pathological changes all provided robust evidence for the efficacy of the applied treatment. Our approach of nerve suture combined with ADSCs injection in treating peripheral nerve injury under real-time NIR-II imaging monitoring in vivo added novel insights into the treatment for peripheral nerve injury, thus further enhancing in-depth understanding of peripheral nerve regeneration and the mechanism behind.
Effects of 17β-Estradiol on Monocyte/Macrophage Response to Staphylococcus aureus: An In Vitro Study
Authors: Souza Clarissa Leal Silva e , Barbosa Camila Dutra , Coelho Hanna I. L. N. , Santos Júnior Manoel N. , Barbosa Elaine Novaes , Queiroz Éllunny Chaves , Teles Mauro Fernandes , dos Santos Déborah Cruz , Bittencourt Rafaela Souza , Soares Telma de Jesus , Oliveira Márcio Vasconcelos , Timenetsky Jorge , Campos Guilherme Barreto , Marques Lucas Miranda
Published: July 2021

To describe how 17β-estradiol (E2) influence in the monocyte/macrophage response induced byS. aureusinin vitromodels of murine peritoneal macrophages (MPMs) and human peripheral blood monocytes (HPBM). MPMs (2 x 105/ml) were isolated from sham (n=3) and ovariectomized (OVX) females (n = 3) and males (n = 3) after induction by thioglycolate. The MPMs obtained from OVX females and males were treated for 24 hours with 17β-estradiol (E2) (10-7M), and after that, inoculation withS. aureuswas carried out for 6 hours. The macrophages were collected and destined to evaluate the relative gene expression of TNF-α, IL-1β, IL-6, IL-8 and TLR2. For thein vitromodel of HPBMs, six men and six women of childbearing age were selected and HPBMs were isolated from samples of the volunteers’ peripheral blood. In women, blood was collected both during menstruation and in the periovulatory period. HPBMs were inoculated withS. aureusfor 6 hours and the supernatant was collected for analysis of cytokines by Luminex and the HPBMs were removed for analysis of 84 genes involved in the host’s response to bacterial infections by RT-PCR array. Previous treatment with E2 decreased the gene expression and production of proinflammatory cytokines, such as TNF-α, IL-1β and IL-6 and decreased the expression of TLR2 tanto em MPMs quanto em HPBMs. The analysis of gene expression shows that E2 inhibited the NFκB pathway. It is suggested that 17β-estradiol acts as an immunoprotective in the monocyte/macrophage response induced byS. aureus.
Prevalence of Cardiovascular Events and Their Risk Factors in Patients With Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea Overlap Syndrome
Authors: Tang Manyun , Long Yunxiang , Liu Shihong , Yue Xin , Shi Tao
Published: July 2021

Rationale: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) have been identified as independent risk factors for cardiovascular diseases. However, the impact of COPD and OSA overlap syndrome (OS) on cardiovascular outcomes remains to be elucidated.

Objective: To determine the prevalence of cardiovascular events and their risk factors in OS patients.

Methods: Seventy-four patients who had OS between January 2015 and July 2020 were retrospectively enrolled, and 222 COPD-only patients and 222 OSA-only patients were pair-matched for age and sex from the same period and served as the OS-free control group. The prevalence rates of coronary heart disease (CHD), arrhythmia, heart failure, and pulmonary arterial hypertension (PAH) were compared among the three groups, and multivariable logistic regression models were used to screen the risk factors for specific cardiovascular events.

Results: OS patients had higher prevalence rates of heart failure (10.8 vs. 0.5 and 1.4%, respectively) and PAH (31.1 vs. 4.5 and 17.1%, respectively) than those with OSA alone or COPD alone (all P < 0.01). The CHD prevalence was also significantly higher in the OS group than in the COPD-alone group (25.7 vs. 11.7%, P < 0.01). There was no significant difference in the prevalence of arrhythmia among the three groups (20.3, 22.5, and 13.1%, respectively, P > 0.05). In OS patients, risk factors for CHD included hypertension, diabetes, body mass index, lactate dehydrogenase level, and tidal volume; risk factors for heart failure included diabetes, partial pressure of oxygen, partial pressure of carbon dioxide, maximum ventilatory volume, and neutrophilic granulocyte percentage; and risk factors for PAH included minimum nocturnal oxygen saturation, partial pressure of carbon dioxide, and brain natriuretic peptide and lactate dehydrogenase levels.

Conclusions: OS patients have a higher prevalence of cardiovascular events, which is associated with hypoxemia, hypercapnia, and impaired lung function in these patients.
Functional and Taxonomic Diversity of Collembola as Complementary Tools to Assess Land Use Effects on Soils Biodiversity
Authors: Joimel Sophie , Schwartz Christophe , Bonfanti Jonathan , Hedde Mickaël , Krogh Paul Henning , Pérès Guénola , Pernin Céline , Rakoto Alain , Salmon Sandrine , Santorufo Lucia , Cortet Jérôme
Published: July 2021

Collembola have been proposed for several decades as a good model organisms to survey soil biodiversity; but most of the studies focused on taxonomic endpoints. The main objectives of this study are to compare the effects of the different land uses, including urban and industrial land uses, while using both collembolan functional and taxonomic biodiversity approaches. We collected data on 3,056 samples of Collembola communities across 758 sites in various land uses throughout France. The types of land use considered included all types of human activity from forestry to urban, industrial, traffic, mining and military areas, agricultural grassland, arable land, vineyards and urban vegetable gardens. In order to study functional and taxonomic biodiversity, we used community-weighted means, functional indices, species richness and density. When looking at collembolan functional diversity, urban and industrial soils appear clearly less diversified than when considering the taxonomic diversity. We suspect here a functional homogenization effect commonly reported in the literature for various organisms in urban ecosystems. Our study provides range of values for different taxonomic and functional indices of Collembola communities in a wide land use classification across France.
Optimization of Genomic Selection to Improve Disease Resistance in Two Marine Fishes, the European Sea Bass (Dicentrarchus labrax) and the Gilthead Sea Bream (Sparus aurata)
Authors: Griot Ronan , Allal François , Phocas Florence , Brard-Fudulea Sophie , Morvezen Romain , Haffray Pierrick , François Yoannah , Morin Thierry , Bestin Anastasia , Bruant Jean-Sébastien , Cariou Sophie , Peyrou Bruno , Brunier Joseph , Vandeputte Marc
Published: July 2021

Disease outbreaks are a major threat to the aquaculture industry, and can be controlled by selective breeding. With the development of high-throughput genotyping technologies, genomic selection may become accessible even in minor species. Training population size and marker density are among the main drivers of the prediction accuracy, which both have a high impact on the cost of genomic selection. In this study, we assessed the impact of training population size as well as marker density on the prediction accuracy of disease resistance traits in European sea bass (Dicentrarchus labrax) and gilthead sea bream (Sparus aurata). We performed a challenge to nervous necrosis virus (NNV) in two sea bass cohorts, a challenge to Vibrio harveyi in one sea bass cohort and a challenge to Photobacterium damselae subsp. piscicida in one sea bream cohort. Challenged individuals were genotyped on 57K–60K SNP chips. Markers were sampled to design virtual SNP chips of 1K, 3K, 6K, and 10K markers. Similarly, challenged individuals were randomly sampled to vary training population size from 50 to 800 individuals. The accuracy of genomic-based (GBLUP model) and pedigree-based estimated breeding values (EBV) (PBLUP model) was computed for each training population size using Monte-Carlo cross-validation. Genomic-based breeding values were also computed using the virtual chips to study the effect of marker density. For resistance to Viral Nervous Necrosis (VNN), as one major QTL was detected, the opportunity of marker-assisted selection was investigated by adding a QTL effect in both genomic and pedigree prediction models. As training population size increased, accuracy increased to reach values in range of 0.51–0.65 for full density chips. The accuracy could still increase with more individuals in the training population as the accuracy plateau was not reached. When using only the 6K density chip, accuracy reached at least 90% of that obtained with the full density chip. Adding the QTL effect increased the accuracy of the PBLUP model to values higher than the GBLUP model without the QTL effect. This work sets a framework for the practical implementation of genomic selection to improve the resistance to major diseases in European sea bass and gilthead sea bream.
Identification of Genomic Regions Influencing N-Metabolism and N-Excretion in Lactating Holstein- Friesians
Authors: Honerlagen Hanne , Reyer Henry , Oster Michael , Ponsuksili Siriluck , Trakooljul Nares , Kuhla Björn , Reinsch Norbert , Wimmers Klaus
Published: July 2021

Excreted nitrogen (N) of dairy cows contribute to environmental eutrophication. The main N-excretory metabolite of dairy cows is urea, which is synthesized as a result of N-metabolization in the liver and is excreted via milk and urine. Genetic variation in milk urea (MU) has been postulated but the complex physiology behind the trait as well as the tremendous diversity of processes regulating the N-metabolism impede the consistent determination of causal regions in the bovine genome. In order to map the genetic determinants affecting N-excretion, MU and eight other N-excretory metabolites in milk and urine were assessed in a genome-wide association study. Therefore phenotypes of 371 Holstein- Friesians were obtained in a trial on a dairy farm under near commercial conditions. Genotype data comprised SNP information of the Bovine 50K MD Genome chip (45,613 SNPs). Significantly associated genomic regions for MU concentration revealed GJA1 (BTA 9), RXFP1, and FRY1 (both BTA 12) as putative candidates. For milk urea yield (MUY) a promising QTL on BTA 17 including SH3D19 emerged, whereas RCAN2, CLIC5, ENPP4, and ENPP5 (BTA 23) are suggested to influence urinary urea concentration. Minor N-fractions in milk (MN) may be regulated by ELF2 and SLC7A11 (BTA 17), whilst ITPR2 and MYBPC1 (BTA 5), STIM2 (BTA 6), SGCD (BTA 7), SLC6A2 (BTA 18), TMCC2 and MFSD4A (BTA 16) are suggested to have an impact on various non-urea-N (NUN) fractions excreted via urine. Our results highlight genomic regions and candidate genes for N-excretory metabolites and provide a deeper insight into the predisposed component to regulate the N-metabolism in dairy cows.
Association of Circulating Follicular Helper T Cells and Serum CXCL13 With Neuromyelitis Optica Spectrum Disorders
Authors: Yang Xiaoyan , Peng Jing , Huang Xiaoxi , Liu Peidong , Li Juan , Pan Jiali , Wei Zhihua , Liu Ju , Chen Min , Liu Hongbo
Published: July 2021

Background

Neuromyelitis optica spectrum disorders (NMOSDs) are severe inflammatory diseases mediated mainly by humoral and cellular immunity. Circulating follicular helper T (Tfh) cells are thought to be involved in the pathogenesis of NMOSD, and serum C-X-C motif ligand 13 (CXCL13) levels reflect the effects of Tfh cells on B-cell-mediated humoral immunity. Immune cell and cytokine changes during the dynamic relapsing and remitting processes in NMOSD require further exploration.

Patients and methods

Blood samples were collected from 36 patients in acute and recovery phases of NMOSD, 20 patients with other noninflammatory neurological diseases (ONND) and 20 age- and sex-matched healthy volunteers. CD4+CXCR5+PD-1+ Tfh cells were detected by flow cytometry, and serum CXCL13 levels were assessed by enzyme-linked immunosorbent assay (ELISA).

Results

The percentage of CD4+CXCR5+PD-1+ Tfh cells was significantly higher during the acute phase than during the recovery phase, and serum CXCL13 levels were significantly higher in patients in the acute and recovery phases of NMOSD than in the ONND and control groups. The Tfh cell percentage was positively correlated with CXCL13 levels, and both were positively correlated with Expanded Disability Status Scale (EDSS) scores and cerebrospinal fluid protein levels in patients with acute NMOSD.

Conclusion

Circulating Tfh cells level has the potential to be a biomarker of disease severity.
Revisiting the Antigen-Presenting Function of β Cells in T1D Pathogenesis
Authors: Li Yang , Sun Fei , Yue Tian-Tian , Wang Fa-Xi , Yang Chun-Liang , Luo Jia-Hui , Rong Shan-Jie , Xiong Fei , Zhang Shu , Wang Cong-Yi
Published: July 2021

Type 1 diabetes (T1D) is characterized by the unresolved autoimmune inflammation and islet β cell destruction. The islet resident antigen-presenting cells (APCs) including dendritic cells and macrophages uptake and process the β cell-derived antigens to prime the autoreactive diabetogenic T cells. Upon activation, those autoreactive T cells produce copious amount of IFN-γ, TNF-α and IL-1β to induce β cell stress and death. Autoimmune attack and β cell damage intertwine together to push forward this self-destructive program, leading to T1D onset. However, β cells are far beyond a passive participant during the course of T1D development. Herein in this review, we summarized how β cells are actively involved in the initiation of autoimmune responses in T1D setting. Specifically, β cells produce modified neoantigens under stressed condition, which is coupled with upregulated expression of MHC I/II and co-stimulatory molecules as well as other immune modules, that are essential properties normally exhibited by the professional APCs. At the cellular level, this subset of APC-like β cells dynamically interacts with plasmacytoid dendritic cells (pDCs) and manifests potency to activate autoreactive CD4 and CD8 T cells, by which β cells initiate early autoimmune responses predisposing to T1D development. Overall, the antigen-presenting function of β cells helps to explain the tissue specificity of T1D and highlights the active roles of structural cells played in the pathogenesis of various immune related disorders.
Site-Specific Glycan-Masking/Unmasking Hemagglutinin Antigen Design to Elicit Broadly Neutralizing and Stem-Binding Antibodies Against Highly Pathogenic Avian Influenza H5N1 Virus Infections
Authors: Chen Ting-Hsuan , Yang Ya-Lin , Jan Jia-Tsrong , Chen Chung-Chu , Wu Suh-Chin
Published: July 2021

The highly pathogenic avian influenza (HPAI) H5N1 viruses with the capability of transmission from birds to humans have a serious impact on public health. To date, HPAI H5N1 viruses have evolved into ten antigenically distinct clades that could cause a mismatch of vaccine strains and reduce vaccine efficacy. In this study, the glycan masking and unmasking strategies on hemagglutinin antigen were used for designing two antigens: H5-dm/st2 and H5-tm/st2, and investigated for their elicited immunity using two-dose recombinant H5 (rH5) immunization and a first-dose adenovirus vector prime, followed by a second-dose rH5 protein booster immunization. The H5-dm/st2 antigen was found to elicit broadly neutralizing antibodies against different H5N1 clade/subclade viruses, as well as more stem-binding antibodies to inhibit HA-facilitated membrane fusion activity. Mice immunized with the H5-dm/st2 antigen had a higher survival rate when challenged with homologous and heterologous clades of H5N1 viruses. Mutant influenza virus replaced with the H5-dm/st2 gene generated by reverse genetics (RG) technology amplified well in MDCK cells and embryonated chicken eggs. Again, the inactivated H5N1-dm/st2 RG virus elicited more potent cross-clade neutralizing and anti-fusion antibodies in sera. Therefore, the H5N1-dm/st2 RG virus with the site-specific glycan-masking on the globular head and the glycan-unmasking on the stem region of H5 antigen can be used for further development of cross-protective H5N1 vaccines.
The Pathogenic Features of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Possible Mechanisms for Immune Evasion?
Authors: Wang Zhihui , Zhou Ming , Fu Zhenfang , Zhao Ling
Published: July 2021

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a newly emerging, highly transmitted and pathogenic coronavirus that has caused global public health events and economic crises. As of March 4, 2021, more than 100 million people have been infected, more than 2 million deaths have been reported worldwide, and the numbers are continuing to rise. To date, a specific drug for this lethal virus has not been developed to date, and very little is currently known about the immune evasion mechanisms of SARS-CoV-2. The aim of this review was to summarize and sort dozens of published studies on PubMed to explore the pathogenic features of SARS-CoV-2, as well as the possible immune escape mechanisms of this virus.
Severe COVID-19 Is Characterized by an Impaired Type I Interferon Response and Elevated Levels of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells
Authors: Dean Matthew J. , Ochoa Juan B. , Sanchez-Pino Maria Dulfary , Zabaleta Jovanny , Garai Jone , Del Valle Luis , Wyczechowska Dorota , Baiamonte Lyndsey Buckner , Philbrook Phaethon , Majumder Rinku , Vander Heide Richard S. , Dunkenberger Logan , Thylur Ramesh Puttalingaiah , Nossaman Bobby , Roberts W. Mark , Chapple Andrew G. , Wu Jiande , Hicks Chindo , Collins Jack , Luke Brian , Johnson Randall , Koul Hari K. , Rees Chris A. , Morris Claudia R. , Garcia-Diaz Julia , Ochoa Augusto C.
Published: July 2021

COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg+G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.
The Role of Macrophages During Mammalian Tissue Remodeling and Regeneration Under Infectious and Non-Infectious Conditions
Authors: Bohaud Candice , Johansen Matt D. , Jorgensen Christian , Kremer Laurent , Ipseiz Natacha , Djouad Farida
Published: July 2021

Several infectious pathologies in humans, such as tuberculosis or SARS-CoV-2, are responsible for tissue or lung damage, requiring regeneration. The regenerative capacity of adult mammals is limited to few organs. Critical injuries of non-regenerative organs trigger a repair process that leads to a definitive architectural and functional disruption, while superficial wounds result in scar formation. Tissue lesions in mammals, commonly studied under non-infectious conditions, trigger cell death at the site of the injury, as well as the production of danger signals favouring the massive recruitment of immune cells, particularly macrophages. Macrophages are also of paramount importance in infected injuries, characterized by the presence of pathogenic microorganisms, where they must respond to both infection and tissue damage. In this review, we compare the processes implicated in the tissue repair of non-infected versus infected injuries of two organs, the skeletal muscles and the lungs, focusing on the primary role of macrophages. We discuss also the negative impact of infection on the macrophage responses and the possible routes of investigation for new regenerative therapies to improve the recovery state as seen with COVID-19 patients.
Differential Expression of microRNAs Correlates With the Severity of Experimental Autoimmune Cystitis
Authors: Kumar Vijay , Kiran Sonia , Shamran Haidar A. , Singh Udai P.
Published: July 2021

Interstitial cystitis (IC)/bladder pain syndrome (BPS) primarily affects women. It varies in its severity and currently has no effective treatment. The symptoms of IC include pelvic pain, urgency and frequency of urination, and discomfort or pain in the bladder and lower abdomen. The bladders of IC patients exhibit infiltration by immune cells, which lends credence to the hypothesis that immune mechanisms also play a role in the etiology and pathophysiology of IC. The Differentially expressed microRNAs (miRs) in immune cells may serve as crucial immunoregulators in the IC. Therefore, we sought to determine whether miRs might play a regulatory role in the progression and pathogenesis of IC, using experimental autoimmune cystitis (EAC) model. In the present study, we observed differential expression of a specific subset of miRs in iliac lymph nodes (ILNs) and urinary bladders (UB) of IC mice compared to that in control mice. Microarray analysis of 96 miRs from the bladder and 135 miRs from ILNs allowed us to identify 50 that exhibited at least a 1.5-fold greater difference in expression in EAC mice compared to control mice. Hierarchical cluster analysis of the microarray data was used to search available databases to predict molecular pathways with which the miRs might interact. Four miRs from each organ that exhibited altered expression in EAC mice and that were predicted to have roles in inflammation (miR-146a, -181, -1931, and -5112) were selected for further analysis by reverse transcription-polymerase chain reaction (RT-PCR). All were confirmed to be elevated in EAC mice. Histological inflammatory scores, systemic chemokines, and cytokines expressed by T helper type 1 (Th1) lymphocytes were also elevated in EAC mice as compared to control animals. We hypothesize that the mechanism of EAC induction might involve the modulation of specific miRs that increase local and systemic levels of chemokines and cytokines. The present study identifies novel miRs expressed in UB and ILNs that will allow us to highlight mechanisms of EAC pathogenesis and may provide potential biomarkers and/or serve as the basis of new therapies for the treatment of IC.
Decadal Dynamics of the CO2 System and Associated Ocean Acidification in Coastal Ecosystems of the North East Atlantic Ocean
Authors: Gac Jean-Philippe , Marrec Pierre , Cariou Thierry , Grosstefan Emilie , Macé Éric , Rimmelin-Maury Peggy , Vernet Marc , Bozec Yann
Published: July 2021

Weekly and bi-monthly carbonate system parameters and ancillary data were collected from 2008 to 2020 in three coastal ecosystems of the southern Western English Channel (sWEC) (SOMLIT-pier and SOMLIT-offshore) and Bay of Brest (SOMLIT-Brest) located in the North East Atlantic Ocean. The main drivers of seasonal and interannual partial pressure of CO2 (pCO2) and dissolved inorganic carbon (DIC) variabilities were the net ecosystem production (NEP) and thermodynamics. Differences were observed between stations, with a higher biological influence on pCO2 and DIC in the near-shore ecosystems, driven by both benthic and pelagic communities. The impact of riverine inputs on DIC dynamics was more pronounced at SOMLIT-Brest (7%) than at SOMLIT-pier (3%) and SOMLIT-offshore (<1%). These three ecosystems acted as a weak source of CO2 to the atmosphere of 0.18 ± 0.10, 0.11 ± 0.12, and 0.39 ± 0.08 mol m–2 year–1, respectively. Interannually, air-sea CO2 fluxes (FCO2) variability was low at SOMLIT-offshore and SOMLIT-pier, whereas SOMLIT-Brest occasionally switched to weak annual sinks of atmospheric CO2, driven by enhanced spring NEP compared to annual means. Over the 2008–2018 period, monthly total alkalinity (TA) and DIC anomalies were characterized by significant positive trends (p-values < 0.001), from 0.49 ± 0.20 to 2.21 ± 0.39 μmol kg−1 year−1 for TA, and from 1.93 ± 0.28 to 2.98 ± 0.39 μmol kg–1 year–1 for DIC. These trends were associated with significant increases of calculated seawater pCO2, ranging from +2.95 ± 1.04 to 3.52 ± 0.47 μatm year–1, and strong reductions of calculated pHin situ, with a mean pHin situ decrease of 0.0028 year–1. This ocean acidification (OA) was driven by atmospheric CO2 forcing (57–66%), Sea surface temperature (SST) increase (31–37%), and changes in salinity (2–5%). Additional pHin situ data extended these observed trends to the 2008–2020 period and indicated an acceleration of OA, reflected by a mean pHin situ decrease of 0.0046 year–1 in the sWEC for that period. Further observations over the 1998–2020 period revealed that the climatic indices North Atlantic Oscillation (NAO) and Atlantic Multidecadal Variability (AMV) were linked to trends of SST, with cooling during 1998–2010 and warming during 2010–2020, which might have impacted OA trends at our coastal stations. These results suggested large temporal variability of OA in coastal ecosystems of the sWEC and underlined the necessity to maintain high-resolution and long-term observations of carbonate parameters in coastal ecosystems.
Fibromyalgia and Associated Disorders: From Pain to Chronic Suffering, From Subjective Hypersensitivity to Hypersensitivity Syndrome
Authors: Maugars Yves , Berthelot Jean-Marie , Le Goff Benoit , Darrieutort-Laffite Christelle
Published: July 2021

The concept of fibromyalgia has progressed to achieve a certain consensus regarding the definition of the condition. We summarize what is known in 2020, be it in terms of diagnosis, with the criteria that have changed over the years, or at the level of the psychological profile, via the notions of “catastrophizing” and “coping” and post-traumatic syndrome. The importance of fatigue and sleep disorders is underlined, with the chronological sequence of post-traumatic syndrome, chronic fatigue, and then amplification of the pain and the onset of multiple associated symptoms. The etiopathogenic debate has been enriched thanks to neuro-imaging data to discover the start of the central neurological signature. The many associated symptoms are reanalyzed in the context of so-called sister conditions which form sometimes more or less separate entities, such as chronic fatigue syndrome or restless legs syndrome for example. What these conditions have in common is hypersensitivity, not just to pain, but also to all exteroceptive stimuli, from deep sensitivity in the neuro-vegetative system, the sense organs and certain functions of the central nervous system, to the psychological aspects and sleep control. In summary, it is possible to define fibromyalgia as a cognitive disorder of cortical integration of chronic pain, with amplification of painful and sensory nociception, decrease in the threshold for the perception of pain, and persistence of a stimulus that maintains the process in chronicity. Fibromyalgia is part of a group of chronic hypersensitivity syndromes of central origin, with a very wide range of means of expression.
Hepatic BRD4 Is Upregulated in Liver Fibrosis of Various Etiologies and Positively Correlated to Fibrotic Severity
Authors: Wu Cichun , Cheng Da , Peng Yanghui , Li Ying , Fu Chunyan , Wang Ying , Fu Lei , Peng Shifang , Ni Xin
Published: July 2021

Bromodomain-containing protein 4 (BRD4) has been implicated to play a regulatory role in fibrogenic gene expression in animal models of liver fibrosis. The potential role of BRD4 in liver fibrosis in humans remains unclear. We sought to investigate the expression and cellular localization of BRD4 in fibrotic liver tissues. Human liver tissues were collected from healthy individuals and patients with liver fibrosis of various etiologies. RNA-seq showed that hepatic BRD4 mRNA was elevated in patients with liver fibrosis compared with that in healthy controls. Subsequent multiple manipulations such as western blotting, real-time quantitative polymerase chain reaction, and dual immunofluorescence analysis confirmed the abnormal elevation of the BRD4 expression in liver fibrosis of various etiologies compared to healthy controls. BRD4 expression was positively correlated with the severity of liver fibrosis, and also correlated with the serum levels of aspartate aminotransferase and total bilirubin. Moreover, the expression of C-X-C motif chemokine ligand 6 (CXCL6), a factor interplayed with BRD4, was increased in hepatic tissues of the patients with liver fibrosis. Its expression level was positively correlated with BRD4 level. BRD4 is up-regulated in liver fibrosis, regardless of etiology, and its increased expression is positively correlated with higher degrees of liver fibrosis. Our data indicate that BRD4 play a critical role in the progress of liver fibrosis, and it holds promise as a potential target for intervention of liver fibrosis.
Uraemic Cardiomyopathy in Different Mouse Models
Authors: Chen Cheng , Xie Caidie , Wu Hanzhang , Wu Lin , Zhu Jingfeng , Mao Huijuan , Xing Changying
Published: July 2021

Uraemic cardiomyopathy (UCM) is one of the most common complications in chronic kidney disease (CKD). Our aim was to compare characteristics of various UCM mouse models. Mice were assigned to the following groups: the pole ligation group, 5/6 nephrectomy group (5/6Nx), uninephrectomy plus contralateral ischemia followed by reperfusion group (IR), adenine group, and sham group. Mice were sacrificed at 4, 8, and 16 weeks after surgery in the pole ligation, 5/6Nx, and IR groups, respectively. In the adenine group, mice were sacrificed at 16 weeks after the adenine diet. The structure and function of the heart and the expression of fibroblast growth factor 23 (FGF-23) and growth differentiation factor 15 (GDF-15) in hearts were assessed. The mortality in the 5/6 Nx group was significantly higher than that in the pole ligation, IR, and adenine groups. Echocardiogram and histological examination showed cardiac hypertrophy in the adenine,5/6Nx, ligation group, and IR group. In addition, cardiac fibrosis occurred in all CKD modeling groups. Interestingly, cardiac fibrosis was more serious in the IR and adenine groups. FGF-23 expression in sham mice was similar to that in modeling groups; however, the GDF-15 level was decreased in modeling groups. Our results suggest that the four models of UCM show different phenotypical features, molding time and mortality. GDF-15 expression in the hearts of UCM mice was downregulated compared with sham group mice.