bluuebunny/crossref_metadata_2025 huggingface dataset:
Pro Nerve Growth Factor and Its Receptor p75NTR Activate Inflammatory Responses in Synovial Fibroblasts: A Novel Targetable Mechanism in Arthritis
Authors: Farina Luciapia , Minnone Gaetana , Alivernini Stefano , Caiello Ivan , MacDonald Lucy , Soligo Marzia , Manni Luigi , Tolusso Barbara , Coppola Simona , Zara Erika , Conti Libenzio Adrian , Aquilani Angela , Magni-Manzoni Silvia , Kurowska-Stolarska Mariola , Gremese Elisa , De Benedetti Fabrizio , Bracci-Laudiero Luisa
Published: March 2022

We have recently provided new evidence for a role of p75NTR receptor and its preferential ligand proNGF in amplifying inflammatory responses in synovial mononuclear cells of chronic arthritis patients. In the present study, to better investigate how activation of the p75NTR/proNGF axis impacts synovial inflammation, we have studied the effects of proNGF on fibroblast-like synoviocytes (FLS), which play a central role in modulating local immune responses and in activating pro-inflammatory pathways. Using single cell RNA sequencing in synovial tissues from active and treatment-naïve rheumatoid arthritis (RA) patients, we demonstrated that p75NTR and sortilin, which form a high affinity receptor complex for proNGF, are highly expressed in PRG4pos lining and THY1posCOL1A1pos sublining fibroblast clusters in RA synovia but decreased in RA patients in sustained clinical remission. In ex vivo experiments we found that FLS from rheumatoid arthritis patients (RA-FLS) retained in vitro a markedly higher expression of p75NTR and sortilin than FLS from osteoarthritis patients (OA-FLS). Inflammatory stimuli further up-regulated p75NTR expression and induced endogenous production of proNGF in RA-FLS, leading to an autocrine activation of the proNGF/p75NTR pathway that results in an increased release of pro-inflammatory cytokines. Our data on the inhibition of p75NTR receptor, which reduced the release of IL-1β, IL-6 and TNF-α, further confirmed the key role of p75NTR activation in regulating inflammatory cytokine production. In a set of ex vivo experiments, we used RA-FLS and cultured them in the presence of synovial fluids obtained from arthritis patients that, as we demonstrated, are characterized by a high concentration of proNGF. Our data show that the high levels of proNGF present in inflamed synovial fluids induced pro-inflammatory cytokine production by RA-FLS. The blocking of NGF binding to p75NTR using specific inhibitors led instead to the disruption of this pro-inflammatory loop, reducing activation of the p38 and JNK intracellular pathways and decreasing inflammatory cytokine production. Overall, our data demonstrate that an active proNGF/p75NTR axis promotes pro-inflammatory responses in synovial fibroblasts, thereby contributing to chronic synovial inflammation, and point to the possible use of p75NTR inhibitors as a novel therapeutic approach in chronic arthritis.
Recurrent Severe Subclinical Mastitis and the Risk of HIV Transmission Through Breastfeeding
Authors: Rutagwera David Gatsinzi , Molès Jean-Pierre , Kankasa Chipepo , Mwiya Mwiya , Tuaillon Edouard , Peries Marianne , Nagot Nicolas , Van de Perre Philippe , Tylleskär Thorkild
Published: March 2022

Subclinical mastitis (SCM) is an important risk factor of postnatal HIV-1 transmission that is still poorly understood. A longitudinal sub-study of the ANRS12174 trial including 270 breastfeeding mothers in Lusaka, Zambia measured sodium (Na+) and potassium (K+) in archived paired breast milk samples collected at week 14, 26 and 38 postpartum to determine cumulative incidence of SCM and the effects of recurrent severe SCM on HIV-1 shedding in breast milk. A nested retrospective cohort study including 112 mothers was also done to determine longitudinal effects of SCM on four pro-inflammatory cytokines; IL6, IL8, IP10 and RANTES. The cumulative incidence for any SCM (Na+/K+ ratio > 0.6) and severe SCM (Na+/K+ ratio > 1) were 58.6% (95%CI: 52.7 – 64.5) and 27.8% (95%CI: 22.5 – 33.1), respectively. In majority of affected mothers (51.4%) severe SCM was recurrent. Both breasts were involved in 11.1%, 33.3% and 70% of the mothers with a single episode, 2 and 3 episodes respectively. In affected breasts, an episode of severe SCM resulted in steep upregulation of the four cytokines considered (IL8, IP10, RANTES and IL6) compared to: before and after the episode; contralateral unaffected breasts; and SCM negative control mothers. Recurrent severe SCM significantly increased the odds of shedding cell-free HIV-1 in breast milk (OR: 5.2; 95%CI: 1.7 – 15.6) whereas single episode of severe SCM did not (OR: 1.8; 95%CI: 0.8 – 4.2). A Na+/K+ ratio > 1 indicative of severe SCM is an excellent indicator of breast inflammation characterized by a steep, localized and temporal upregulation of several pro-inflammatory cytokines that favor HIV-1 shedding in mature breast milk and may facilitate postnatal HIV-1 transmission through breastfeeding.
Mesenchymal Stem Cell-Derived Extracellular Vesicles in Liver Immunity and Therapy
Authors: Wu Ruiqi , Fan Xiaoli , Wang Yi , Shen Mengyi , Zheng Yanyi , Zhao Shenglan , Yang Li
Published: March 2022

Mesenchymal stem cells (MSCs), as the most common cell source for stem cell therapy, play an important role in the modulation of innate and adaptive immune responses and have been widely used in clinical trials to treat autoimmune and inflammatory diseases. Recent experimental and clinical studies have shown that MSC-derived extracellular vesicles (MSC-EVs) can inhibit the activation and proliferation of a variety of proinflammatory cells, such as Th1, Th17 and M1 macrophages, reducing the secretion of proinflammatory cytokines, while promoting the proliferation of anti-inflammatory cells, such as M2 macrophages and Tregs, and increasing the secretion of anti-inflammatory cytokines, thus playing a role in immune regulation and exhibiting immunomodulatory functions. Besides MSC-EVs are more convenient and less immunogenic than MSCs. There is growing interest in the role of MSC-EVs in liver diseases owing to the intrinsic liver tropism of MSC-EVs. In this review, we focus on the immunomodulatory effects of MSC-EVs and summarize the pivotal roles of MSC-EVs as a cell-free therapy in liver diseases, including NAFLD, AIH, acute liver failure, liver fibrosis and hepatic ischemia–reperfusion injury. Moreover, we provide a concise overview of the potential use and limits of MSC-EVs in clinical application.
Molecular Evolution of Transforming Growth Factor-β (TGF-β) Gene Family and the Functional Characterization of Lamprey TGF-β2
Authors: Liu Siqi , Guo Junfu , Cheng Xianda , Li Wenna , Lyu Shuangyu , Chen Xuanyi , Li Qingwei , Wang Hao
Published: March 2022

The transforming growth factor-βs (TGF-βs) are multifunctional cytokines capable of regulating a wide range of cellular behaviors and play a key role in maintaining the homeostasis of the immune system. The TGF-β subfamily, which is only present in deuterostomes, expands from a single gene in invertebrates to multiple members in jawed vertebrates. However, the evolutionary processes of the TGF-β subfamily in vertebrates still lack sufficient elucidation. In this study, the TGF-β homologs are identified at the genome-wide level in the reissner lamprey (Lethenteron reissneri), the sea lamprey (Petromyzon marinus), and the Japanese lamprey (Lampetra japonica), which are the extant representatives of jawless vertebrates with a history of more than 350 million years. The molecular evolutionary analyses reveal that the lamprey TGF-β subfamily contains two members representing ancestors of TGF-β2 and 3 in vertebrates, respectively, but TGF-β1 is absent. The transcriptional expression patterns show that the lamprey TGF-β2 may play a central regulatory role in the innate immune response of the lamprey since it exhibits a more rapid and significant upregulation of expression than TGF-β3 during lipopolysaccharide stimuli. The incorporation of BrdU assay reveals that the lamprey TGF-β2 recombinant protein exerts the bipolar regulation on the proliferation of the supraneural myeloid body cells (SMB cells) in the quiescent and LPS-activated state, while plays an inhibitory role in the proliferation of quiescent and activated leukocytes in lampreys. Furthermore, caspase-3/7 activity analysis indicates that the lamprey TGF-β2 protects SMB cells from apoptosis after serum deprivation, in contrast to promoting apoptosis of leukocytes. Our composite results offer valuable clues to the origin and evolution of the TGF-β subfamily and imply that TGF-βs are among the most ancestral immune regulators in vertebrates.
Role of the CXCL13/CXCR5 Axis in Autoimmune Diseases
Authors: Pan Zijian , Zhu Tong , Liu Yanjun , Zhang Nannan
Published: March 2022

CXCL13 is a B-cell chemokine produced mainly by mesenchymal lymphoid tissue organizer cells, follicular dendritic cells, and human T follicular helper cells. By binding to its receptor, CXCR5, CXCL13 plays an important role in lymphoid neogenesis, lymphoid organization, and immune responses. Recent studies have found that CXCL13 and its receptor CXCR5 are implicated in the pathogenesis of several autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, primary Sjögren’s syndrome, myasthenia gravis, and inflammatory bowel disease. In this review, we discuss the biological features of CXCL13 and CXCR5 and the recent findings on the pathogenic roles of the CXCL13/CXCR5 axis in autoimmune diseases. Furthermore, we discuss the potential role of CXCL13 as a disease biomarker and therapeutic target in autoimmune diseases.
Oral Vaccination With Recombinant Pichia pastoris Expressing Iridovirus Major Capsid Protein Elicits Protective Immunity in Largemouth Bass (Micropterus salmoides)
Authors: Yao Jia-Yun , Zhang Cheng-Sai , Yuan Xue-Mei , Huang Lei , Hu Da-Yan , Yu Zhe , Yin Wen-Lin , Lin Ling-Yun , Pan Xiao-Yi , Yang Gui-lian , Wang Chun-Feng , Shen Jin-Yu , Zhang Hai-Qi
Published: March 2022

Largemouth bass iridovirus (LMBV) can cause high mortality and lead to heavy economic loss in the cultivation of largemouth bass, but there was no effective treatment. Here, the present study constructed a recombinant Pichia pastoris expressing LMBV major capsid protein (MCPD). The recombinant GS115-pW317-MCPD was then used to immunize largemouth bass via oral administration, and mucosal immune response mediated by immunoglobulins (Igs) was measured after oral immunization. Serum antibody levels were measured by ELISA, neutralizing antibody titers were determined by serum neutralization test (SNT), antigen presentation-related gene expressions were detected by RT-PCR, and the histopathological characteristics of immunized fish were assessed after challenging with 0.1 ml 107.19 TCID50/ml LMBV. The relative percentage survival (RPS) was also determined. Our results showed that the serum antibody titers of immunized fish were significantly higher than that of control groups (P < 0.05). IgT and IgM expressions in gut were increased significantly after vaccination with GS115-pW317-MCPD; however, much stronger response in gut was observed as compared with gill. The expression levels of major histocompatibility complex (MHC) II, CD8, and T-cell receptor (TCR) were significantly elevated in GS115-pW317-MCPD group (P < 0.05), while CD4 and MHC I transcription levels remained unchanged after oral immunization (P > 0.05). The RPS of fish orally immunized with 1.0 × 108 CFU/g GS115-pW317-MCPD was reached up to 41.6% after challenge with 0.1 ml 109.46 TCID50/ml LMBV. Moreover, orally immunizing with GS115-pW317-MCPD can relieve the pathological damage caused by LMBV. Therefore, GS115-pW317-MCPD showed a promising potential against LMBV.
An Acute Permethrin Exposure Causes Significant Microbial Shifts in Montastraea cavernosa
Authors: MacKnight Nicholas J. , Arick Lindsay , Crawford Amelia C. , Henry Michael , Pierce Richard , Muller Erinn M.
Published: March 2022

Insecticide use is common in developed tropical regions where it may enter coastal reef ecosystems through land-based sources. This local introduction of contaminants could affect ecosystem health as corals can better withstand global stressors more readily if local pressures are reduced. The present study investigated the microbial community and photochemical efficiency of the reef building coral, Montastraea cavernosa, when exposed to the commercially applied insecticide, permethrin. Montastraea cavernosa was exposed to an acute concentration of permethrin for 24 h in a controlled laboratory setting. Fourteen fragments were integrated across four treatments (2 or 0.325 μg/l of permethrin, acetone control, and saltwater control) with three to four replicates per treatment. Photosynthetic efficiency was measured by quantifying the maximum photochemical yield and maximum electron transport rate (ETR), which were recorded for each fragment before exposure and 24 h after exposure to permethrin. The microbial communities of M. cavernosa tissue was measured using 16S rRNA sequencing for each fragment. Permethrin exposure at the tested concentrations suggested no significant effect on the M. cavernosa’s photochemical parameters measured during the 24-h permethrin exposure. Microbial communities were significantly different between permethrin treated (2 and 0.325 μg/l) and non-treated conditions (acetone and saltwater controls). In permethrin treated coral, this study documented a significant increase in Burkholderia pyroccinnia and Bacillus sp., bacteria groups known to bioremediate insecticides. Exposure of permethrin also decreased the relative abundance of Mesorhizobium sp., Sediminibacterium sp., Sphingorhabdus sp., and Chondromyces sp., which are known to inhibit pathogen colonization and provide essential macromolecules. Therefore, although the symbiotic relationship between the host and the intracellular algae remained intact after the corals were exposed to permethrin, the significant shift in the microbiome indicate permethrin may destabilize the microbial composition of the holobiont.
Expert Knowledge-Driven Bayesian Network Modeling for Marine Disaster Assessment Under the Small Sample Condition
Authors: Li Ming , Zhang Ren , Liu Kefeng
Published: March 2022

Risk assessment and management of marine disasters are the prerequisite of ocean exploitation and utilization. Marine disaster assessment is a complicated system engineering with high non-linearity and uncertainty. To deal with the problem, Bayesian network (BN) has become a powerful model used for disaster assessment due to its capability of expressing complex relationships and reasoning with uncertainty. However, scarce data sets and case samples of marine disasters pose an obstacle to BN modeling, particularly for structure and parameter learning. In our research, we combine expert knowledge with small sample to propose a new BN-based assessment model. Expert knowledge is regularly expressed and quantitatively incorporated into BN learning with DS evidence theory. Then, the genetic algorithm is adopted to search the optimal network parameters. Comparative experiments show that the new model has a better assessment accuracy (91.03%) than BPNN (61.34%) and SVM (70.67%), especially with small samples. The proposed model achieves the risk assessment of marine disasters under the small sample condition, providing the technical support for marine disaster prevention and mitigation.
The Multi-Ocean Distribution of the Hadal Amphipod, Hirondellea dubiaDahl, 1959 (Crustacea, Amphipoda)
Authors: Weston Johanna N. J. , Jamieson Alan J.
Published: March 2022

The hadal zone (depths > 6,000 m) comprises isolated features that host high degrees of endemism, with species inhabiting only a single feature or a group of adjacent features. The amphipod, Hirondellea dubia is an abundant scavenger at the hadal depths of the Kermadec, Tonga, and New Hebrides trenches in the Southwest Pacific Ocean, particularly at depths > 9,500 m. However, several records have hinted that H. dubia may not be restricted to the Southwest Pacific nor be exclusively hadal. Here, we present new records of H. dubia recovered by baited landers deployed to five hadal trenches during three expeditions and assess the geographic and vertical distribution of this species. To rule out the possibility of cryptic diversity, morphological taxonomy was paired with two mitochondrial markers (16S and COI) to test for species boundaries among the new and published molecular data using four delineation approaches (ABGD, CD-HIT, GMYC, and bPTP). We found H. dubia to be a single species and not restricted to the Southwest Pacific or hadal depths. This species’ geographic range extends from the Southwest Pacific to the Mariana Trench (Northwest Pacific), the Clarion-Clipperton Zone (Central Pacific), the South Sandwich Trench (Southern), and the Puerto Rico Trench (North Atlantic). This amphipod’s vertical range spans over half of the ocean’s total depth, between 4,700 and 10,817 m. This study presents an extraordinary geographic range extension to a species long considered endemic to a cluster of three Southwest Pacific trenches and shows a pan-oceanic distribution across extremely isolated hadal features.
Optical Properties and Dynamic Extrinsic Chirality of Structured Monolayer Black Phosphorus
Authors: Sun Mengke , Wang Ying , Hu Hui , Zhang Hao , Li Wenjia , Lv Bo , Zhu Zheng , Guan Chunying , Shi Jinhui
Published: March 2022

Chiral metamaterials have drawn increasing attention due to their strong chiral responses. Monolayer black phosphorus is a tunable two-dimensional material with anisotropy that plays an important role in a variety of fields such as chirality and polarization control. In this work, we propose a metamaterial with structured monolayer black phosphorus to manipulate the transmission properties of circularly polarized waves. The metamaterial exhibits strong circular dichroism and circular birefringence effects depending on oblique incidence of the circularly polarized wave and has a weaker circular conversion dichroism effect as well. Moreover, this work also investigates effects of different chiral phenomena of the metamaterial on various structural parameters as well as incident angles and the electron concentration. It has been proved that the electron concentration of monolayer black phosphorus can dynamically tune the chirality properties. Remarkably, the non-zero pure optical activity always occurs at one certain frequency regardless of the elevation angle and the azimuthal angle. The proposed framework provides opportunities for designing meta-devices with monolayer black phosphorus and practical potentials for novel and high-performance infrared metamaterials.
Nasal Microbiome Change During and After Exacerbation in Asthmatic Children
Authors: Liu Tsunglin , Lin Cheng-Han , Chen Yi-Lin , Jeng Shuen-Lin , Tsai Hui-Ju , Ho Chung-Liang , Kuo Wen-Shuo , Hsieh Miao-Hsi , Chen Pei-Chi , Wu Lawrence Shih-Hsin , Wang Jiu-Yao
Published: March 2022

Airway and gut microbiota are important in asthma pathogenesis. Although several studies have revealed distinct microbiota in asthmatic airways at baseline compared to healthy controls, limited studies compared microbiota during acute exacerbation (AE) and in the recovery phase (RP) in the same asthmatic children. We aim to investigate association between microbiota and asthma status in children and explore their relationship with clinical features of asthma. We recruited 56 asthmatic children and investigated their nasal, throat, and stool microbiota during AE and in the RP. Totally, 320 samples were subjected to 16S rRNA sequencing. Although the microbial communities were clearly separated by body site, within each site the overall communities during AE and in the RP could not be distinguished. Most nasal microbiota were dominated by only one or two of six bacterial genera. The domination was associated with mite allergy and patient age only during AE but not in the RP. When moving into RP, the relative abundance of Staphylococcus increased while that of Moraxella decreased. Throat and stool microbiota were not associated with most of the clinical features. Interestingly, stool microbiota during AE was associated with ABO blood type and stool microbiota in the RP was associated with frequency of the subsequent exacerbations. In summary, the association between nasal microbiota and mite allergy only during AE suggests an altered local immunity and its interplay with nasal microbes. Our work provides a basis for studying microbes, and prevention or therapeutic strategy in childhood asthma, especially during AE.
Systematic Tracing of Susceptible Animals to SARS-CoV-2 by a Bioinformatics Framework
Authors: Sun Hailiang , Wang Ailan , Wang Lixia , Wang Bing , Tian Geng , Yang Jialiang , Liao Ming
Published: March 2022

Since the outbreak of SARS-CoV-2 in 2019, the Chinese horseshoe bats were considered as a potential original host of SARS-CoV-2. In addition, cats, tigers, lions, mints, and ferrets were naturally or experimentally infected with SARS-CoV-2. For the surveillance and control of this highly infectious disease, it is critical to trace susceptible animals and predict the consequence of potential mutations at the binding region of viral spike protein and host ACE2 protein. This study proposed a novel bioinformatics framework to systematically trace susceptible animals to SARS-CoV-2 and predict the binding affinity between susceptible animals’ mutated/un-mutated ACE2 receptors. As a result, we identified a few animals posing a potential risk of infection with SARS-CoV-2 using the docking analysis of ACE2 protein and viral spike protein. The binding affinity of some of these species is weaker than that of humans but more potent than that of Chinese horseshoe bats. We also found that a few point mutations in human ACE2 protein or viral spike protein could significantly enhance their binding affinity, posing an enormous potential threat to public health. The ancestors of the Omicron may evolve rapidly through the accumulation of mutations in infecting the host and jumped into human beings. These findings indicate that if the epidemic expands, there may be a human-animal-human transmission route, which will increase the difficulty of disease prevention and control.
Antarctic Glacial Meltwater Impacts the Diversity of Fungal Parasites Associated With Benthic Diatoms in Shallow Coastal Zones
Authors: Ilicic Doris , Woodhouse Jason , Karsten Ulf , Zimmermann Jonas , Wichard Thomas , Quartino Maria Liliana , Campana Gabriela Laura , Livenets Alexandra , Van den Wyngaert Silke , Grossart Hans-Peter
Published: March 2022

Aquatic ecosystems are frequently overlooked as fungal habitats, although there is increasing evidence that their diversity and ecological importance are greater than previously considered. Aquatic fungi are critical and abundant components of nutrient cycling and food web dynamics, e.g., exerting top-down control on phytoplankton communities and forming symbioses with many marine microorganisms. However, their relevance for microphytobenthic communities is almost unexplored. In the light of global warming, polar regions face extreme changes in abiotic factors with a severe impact on biodiversity and ecosystem functioning. Therefore, this study aimed to describe, for the first time, fungal diversity in Antarctic benthic habitats along the salinity gradient and to determine the co-occurrence of fungal parasites with their algal hosts, which were dominated by benthic diatoms. Our results reveal that Ascomycota and Chytridiomycota are the most abundant fungal taxa in these habitats. We show that also in Antarctic waters, salinity has a major impact on shaping not just fungal but rather the whole eukaryotic community composition, with a diversity of aquatic fungi increasing as salinity decreases. Moreover, we determined correlations between putative fungal parasites and potential benthic diatom hosts, highlighting the need for further systematic analysis of fungal diversity along with studies on taxonomy and ecological roles of Chytridiomycota.
Sedimentary Nitrogen and Sulfur Reduction Functional-Couplings Interplay With the Microbial Community of Anthropogenic Shrimp Culture Pond Ecosystem
Authors: Zhou Renjun , Hou Dongwei , Zeng Shenzheng , Wei Dongdong , Yu Lingfei , Bao Shicheng , Weng Shaoping , He Jianguo , Huang Zhijian
Published: March 2022

Sediment nitrogen and sulfur cycles are essential biogeochemical processes that regulate the microbial communities of environmental ecosystems, which have closely linked to environment ecological health. However, their functional couplings in anthropogenic aquaculture sedimentary ecosystems remain poorly understood. Here, we explored the sediment functional genes in shrimp culture pond ecosystems (SCPEs) at different culture stages using the GeoChip gene array approach with 16S amplicon sequencing. Dissimilarity analysis showed that the compositions of both functional genes and bacterial communities differed at different phases of shrimp culture with the appearance of temporal distance decay (p < 0.05). During shrimp culture, the abundances of nitrite and sulfite reduction functional genes decreased (p < 0.05), while those of nitrate and sulfate reduction genes were enriched (p < 0.05) in sediments, implying the enrichment of nitrites and sulfites from microbial metabolism. Meanwhile, nitrogen and sulfur reduction genes were found to be linked with carbon degradation and phosphorous metabolism (p < 0.05). The influence pathways of nutrients were demonstrated by structural equation modeling through environmental factors and the bacterial community on the nitrogen and sulfur reduction functions, indicating that the bacterial community response to environmental factors was facilitated by nutrients, and led to the shifts of functional genes (p < 0.05). These results indicate that sediment nitrogen and sulfur reduction functions in SCPEs were coupled, which are interconnected with the SCPEs bacterial community. Our findings will be helpful for understanding biogeochemical cycles in anthropogenic aquaculture ecosystems and promoting sustainable management of sediment environments through the framework of an ecological perspective.
Dynamics of phoD- and gcd-Harboring Microbial Communities Across an Age Sequence of Biological Soil Crusts Under Sand-Fixation Plantation
Authors: Zhao Xingxing , Zhang Ying , Cui Zhenbo , Peng Lu , Cao Chengyou
Published: March 2022

Biological soil crusts (BSCs) are important for restoring vegetation and improving soil fertility in arid or semiarid desertified land. However, studies on the contribution of BSC microbes to phosphorus (P) transformation remains limited. The microbial diversity involved in P transformation and its dynamic along BSC development should be examined to further understand the microbial regulatory mechanism of the P-cycling process. This paper investigates the soil properties, P fractions, and potential of P transformation across a chronosequence (0-, 8-, 20-, and 35-year) of the BSC underCaragana microphyllaplantation on the moving sand dunes in Horqin Grassland, China. An abundance ofphoDandgcdgenes was detected, and the diversities and structures ofphoD- andgcd-haboring microbial communities were illustratedviahigh-throughput sequencing. Soil nutrient content, activity of alkaline phosphomonoesterase, potential of organic P (OP) mineralization, and the abundance ofphoDandgcdgenes all linearly increased along with BSC age. The microbial quantity and species diversity of thephoDcommunity were greater than those ofgcd. BSC development increased the availability of inorganic P (IP) fractions, and both NaHCO3-Pi and NaOH-Pi were positively correlated with the abundance of the two genes and the activity of alkaline phosphomonoesterase. The phyla of Actinobacteria, Planctomycetes, and Proteobacteria and the family ofStreptomycetaceaewere the most dominant taxa in thephoDcommunity, Proteobacteria was the dominant phylum in thegcdcommunity in BSC soils, andRhizobiumandPlanctomyceswere the most dominant genera. The dominant taxa quantitatively responded to soil property improvement, but the basic compositions and dominant taxa did not change along with BSC development. The structures ofphoDandgcdcommunities were linked to soil properties, and pH available K, and total K tend to be the direct determining factors.
Species Diversity and Virulence Potential of the Beauveria bassiana Complex and Beauveria scarabaeidicola Complex
Authors: Wang Yao , Fan Qi , Wang Dong , Zou Wei-Qiu , Tang De-Xiang , Hongthong Preeyanat , Yu Hong
Published: March 2022

Beauveria is a very important fungal resource. Some Beauveria species have great economic and ecological value. Through surveying Beauveria in China and Thailand over the past 4 years, 15 Beauveria spp. were collected and identified. Three new species—namely, B. polyrhachicola, B. songmingensis, and B. subscarabaeidicola—were described and illustrated based on morphological characteristics and molecular data. The phylogenetic positions of the 15 species were evaluated according to phylogenetic inferences based on six loci (nrSSU, nrLSU, TEF, RPB1, RPB2, and Bloc). Nine species of Beauveria in our study were isolated from adult scarab beetles (Coleoptera: Scarabaeidae). The pathogenicity of the isolates from the B. bassiana complex and B. scarabaeidicola complex was determined with three bioassays using B. mori and T. molitor larvae, in addition to Protaetia brevitarsis adults. The results indicated that the B. bassiana complex isolates had great potential in the biocontrol of the three insects; by contrast, the B. scarabaeidicola complex isolates showed obvious host specificity and low virulence.
Transcriptome Analyses of Senecavirus A-Infected PK-15 Cells: RIG-I and IRF7 Are the Important Factors in Inducing Type III Interferons
Authors: Peng Kenan , Deng Lishuang , Wei Jianfeng , Zhao Jun , Deng Huidan , Tao Qian , Jiang Chaoyuan , Zeng Yubing , Li Fei , Zhang Rubo , Sun Xiangang , Xu Zhiwen , Zhu Ling
Published: March 2022

Senecavirus A (SVA) is a new type of virus related to swine vesicular disease, which results in enormous economic losses worldwide. At present, the host transcriptional responses to SVA infection, host-SVA interactions, and the mechanism of SVA in innate immune modulation are not well understood. This study explores the gene expression profiles of PK-15 cells at 0, 6, 12, 18, 24, 36 h SVA post-infection by RNA sequencing. Our analysis identified 61, 510, 1,584, 2,460, and 2,359 differentially expressed genes (DEGs) in the comparison groups S6 vs. Control, S12 vs. Control, S18 vs. Control, S24 vs. Control, S36 vs. Control, respectively. The reproducibility and repeatability of the results were validated by RT-qPCR, and all DEGs exhibited expression patterns consistent with the RNA-seq results. According to GO enrichment analysis and KEGG pathway analysis of DEGs in different periods after SVA infection, we found that SVA infection significantly modified the host cell gene-expression patterns and the host cells responded in highly specific manners, including response to signal reception and transmission, external biotic stimulus, response to the virus and host immune defense response. Notably, we observed the specific induction of type III interferon IFN-λ1 and IFN-λ3, which indicated that type III interferon plays an important antiviral function in PK-15 cells. Furthermore, our results showed that SVA might be recognized by RIG-I/MDA-5 receptors first after infecting PK-15 cells and then activates downstream IRF7-mediated signaling pathways, causing an increase in the expression of type III interferon. This study could provide important insights into the modulation of host metabolism during SVA infection and provide a strong theoretical basis for a better understanding of the pathogenic mechanism and immune escape mechanism of SVA.
Innate Immune Evasion by Human Respiratory Syncytial Virus
Authors: Ouyang Yan , Liao Hongqun , Hu Yan , Luo Kaiyuan , Hu Shaowen , Zhu Huifang
Published: March 2022

Respiratory syncytial virus (RSV) is the leading cause of severe respiratory infection in young children. Nearly all individuals become infected in their early childhood, and reinfections with RSV are common throughout life. Primary infection with RSV is usually involved in the symptom of bronchiolitis and pneumonia in the lower respiratory tract, which accounts for over 3 million hospitalizations and approximately 66,000 deaths annually worldwide. Despite the widespread prevalence and high morbidity and lethality rates of diseases caused by RSV infection, there is currently no licensed RSV vaccine. During RSV infection, innate immunity plays the first line of defense to suppress RSV infection and replication. However, RSV has evolved multiple mechanisms to evade the host’s innate immune responses to gain a window of opportunity for efficient viral replication. This review discusses the comprehensive interaction between RSV infection and the host antiviral innate immunity and updates recent findings on how RSV modulates the host innate immune response for survival, which may provide novel insights to find potent drug targets and vaccines against RSV.
Causal Relationships Between Osteoarthritis and Senile Central Nerve System Dysfunction: A Bidirectional Two-Sample Mendelian Randomization Study
Authors: Cai Yuanqing , Zhang Guangyang , Liang Jialin , Jing Zhaopu , Zhang Rupeng , Lv Leifeng , Dang Xiaoqian
Published: March 2022

Background

The relationship between osteoarthritis (OA) and senile central nervous system dysfunctions (CNSDs), including Parkinson’s disease (PD), Alzheimer’s disease (AD), and ischemic stroke (IS) has gradually attracted attention. At present, the causal relationship between OA and CNSD remains unclear. The aim of this study was to assess the causal effects of CNSD and OA using Mendelian randomization (MR).

Methods

Genome-wide association study summary data for CNSD and OA were obtained. Single-nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs), and significant (P < 5.0 × 10–8) and independent (r2 < 0.1) SNPs were extracted for bidirectional MR analysis. Inverse variance weighted (IVW) was used to assess these causal relationships. The results are reported as odds ratios (ORs). Subsequently, heterogeneity was tested using the Cochran’s Q test, pleiotropy was tested using the MR-Egger intercept, and sensitivity analysis was performed using the leave-one-out sensitivity test.

Results

The MR results of the causal relationship between PD and OA showed that there was a positive causal effect of OA on PD, which was estimated by IVW (OR = 1.194, 95%CI = 1.036, 1.378; P = 0.0144). Moreover, the MR analysis by IVW also showed that IS had a positive effect on OA (OR = 1.033, 95%CI = 1.002, 1.066; P = 0.0355). These results are reliable and stable, as confirmed by sensitivity tests.

Conclusion

This study showed a positive causal effect of OA on PD, but there was a null effect of OA on AD and OA on IS.
Unified Deep Learning-Based Mouse Brain MR Segmentation: Template-Based Individual Brain Positron Emission Tomography Volumes-of-Interest Generation Without Spatial Normalization in Mouse Alzheimer Model
Authors: Seo Seung Yeon , Kim Soo-Jong , Oh Jungsu S. , Chung Jinwha , Kim Seog-Young , Oh Seung Jun , Joo Segyeong , Kim Jae Seung
Published: March 2022

Although skull-stripping and brain region segmentation are essential for precise quantitative analysis of positron emission tomography (PET) of mouse brains, deep learning (DL)-based unified solutions, particularly for spatial normalization (SN), have posed a challenging problem in DL-based image processing. In this study, we propose an approach based on DL to resolve these issues. We generated both skull-stripping masks and individual brain-specific volumes-of-interest (VOIs—cortex, hippocampus, striatum, thalamus, and cerebellum) based on inverse spatial normalization (iSN) and deep convolutional neural network (deep CNN) models. We applied the proposed methods to mutated amyloid precursor protein and presenilin-1 mouse model of Alzheimer’s disease. Eighteen mice underwent T2-weighted MRI and 18F FDG PET scans two times, before and after the administration of human immunoglobulin or antibody-based treatments. For training the CNN, manually traced brain masks and iSN-based target VOIs were used as the label. We compared our CNN-based VOIs with conventional (template-based) VOIs in terms of the correlation of standardized uptake value ratio (SUVR) by both methods and two-sample t-tests of SUVR % changes in target VOIs before and after treatment. Our deep CNN-based method successfully generated brain parenchyma mask and target VOIs, which shows no significant difference from conventional VOI methods in SUVR correlation analysis, thus establishing methods of template-based VOI without SN.
The Association of Pre-existing Diagnoses of Alzheimer’s Disease and Parkinson’s Disease and Coronavirus Disease 2019 Infection, Severity and Mortality: Results From the Korean National Health Insurance Database
Authors: Kim Ji Hee , Chang In Bok , Kim Yoo Hwan , Min Chan Yang , Yoo Dae Myoung , Choi Hyo Geun
Published: March 2022

Objectives

Despite the numerous studies on coronavirus disease 2019 (COVID-19), data regarding the impact of pre-existing diagnoses of Alzheimer’s disease (AD) and Parkinson’s disease (PD) on the susceptibility to and outcome of COVID-19 are limited. We aimed to determine whether patients with AD/PD had a higher likelihood of contracting COVID-19 and experiencing worse outcomes.

Methods

Data from patients with confirmed diagnoses of COVID-19 (n = 8,070) from January to June 2020 and control participants (n = 121,050) who were randomly selected to match the patients on the basis of age and sex were extracted from the Korean National Health Insurance Database. Pre-existing diagnoses of AD and PD were identified based on medical claim codes. The associations of pre-existing AD or PD with contracting COVID-19, developing severe COVID-19 and dying due to COVID-19 were examined using a logistic regression model. The participants’ age, sex, income, comorbidity score, and history of hypertension/diabetes were assessed as covariates.

Results

COVID-19 cases were more likely to have a pre-existing AD diagnosis (adjusted odds ratio [aOR] = 2.11, 95% confidence interval [CI] = 1.79–2.50, P-value < 0.001) than controls. COVID-19 cases were more likely to have a pre-existing PD diagnosis than controls, although this estimate did not quite reach statistical significance (aOR = 1.41, 95% CI = 1.00–2.00, P-value = 0.054). Pre-existing AD was related to severe disease and mortality from COVID-19 (aOR = 2.21, 95% CI = 1.64–2.98; aOR = 2.21, 95% CI = 1.00–2.00). Pre-existing PD was not associated with mortality (aOR = 1.54, 95% CI = 0.75–3.16) but was associated with severe disease (aOR = 2.89, 95% CI = 1.56–5.35).

Conclusion

We found that COVID-19 infection was significantly associated with a pre-existing diagnosis of AD but not with a pre-existing diagnosis of PD. Patients with pre-existing AD had higher odds of developing severe COVID-19 and dying. Pre-existing PD was only associated with a higher odds of developing severe COVID-19.
Siamese Network-Based All-Purpose-Tracker, a Model-Free Deep Learning Tool for Animal Behavioral Tracking
Authors: Su Lihui , Wang Wenyao , Sheng Kaiwen , Liu Xiaofei , Du Kai , Tian Yonghong , Ma Lei
Published: March 2022

Accurate tracking is the basis of behavioral analysis, an important research method in neuroscience and many other fields. However, the currently available tracking methods have limitations. Traditional computer vision methods have problems in complex environments, and deep learning methods are hard to be applied universally due to the requirement of laborious annotations. To address the trade-off between accuracy and universality, we developed an easy-to-use tracking tool, Siamese Network-based All-Purpose Tracker (SNAP-Tracker), a model-free tracking software built on the Siamese network. The pretrained Siamese network offers SNAP-Tracker a remarkable feature extraction ability to keep tracking accuracy, and the model-free design makes it usable directly before laborious annotations and network refinement. SNAP-Tracker provides a “tracking with detection” mode to track longer videos with an additional detection module. We demonstrate the stability of SNAP-Tracker through different experimental conditions and different tracking tasks. In short, SNAP-Tracker provides a general solution to behavioral tracking without compromising accuracy. For the user’s convenience, we have integrated the tool into a tidy graphic user interface and opened the source code for downloading and using (https://github.com/slh0302/SNAP).
Lessons Learned From the Historical Trends on Thrombolysis Use for Acute Ischemic Stroke Among Medicare Beneficiaries in the United States
Authors: Meng Tong , Trickey Amber W. , Harris Alex H. S. , Matheson Loretta , Rosenthal Sarah , Traboulsi Abd Al-Rahman , Saver Jeffrey L. , Wagner Todd , Govindarajan Prasanthi
Published: March 2022

Background

The most recent time trends on intravenous thrombolysis (IVT) utilization for acute ischemic stroke was reported in 2011 using the Get with the Guidelines. Our objectives are to assess and validate the change in IVT utilization through 2014 in a national sample of Medicare beneficiaries and to examine the effect of patient, stroke center designation, and geography on IVT utilization.

Methods

We built a comprehensive national stroke registry by combining patient-level, stroke center status, and geographical characteristics, using multiple data sources. Using multiple national administrative databases from 2007 to 2014, we generated a mixed-effect logistic regression model to characterize the independent associations of patient, hospital, and geographical characteristics with IVT in 2014.

Results

Use of IVT increased consistently from 2.8% in 2007 to 7.7% in 2014, P < 0.001. Between group differences persisted, with lower odds of use in patients who were ≥86 years (aOR 0.74, 95% CI 0.65–0.83), Black (aOR 0.73, 95% CI 0.61–0.87), or treated at a rural hospital (aOR 0.88, 95% CI 0.77–1.00). Higher odds of use were observed in patients who arrived by ambulance (aOR 2.67, 95% CI 2.38–3.00), were treated at a hospital certified as a stroke center (aOR 1.96, 95% CI 1.68–2.29), or were treated at hospitals located in the most socioeconomically advantaged areas (aOR 1.27, 95% CI 1.05–1.54).

Conclusions

Between 2007 and 2014, the frequency of IVT for patients with acute ischemic stroke increased substantially, though differences persisted in the form of less frequent treatment associated with certain characteristics. These findings can inform ongoing efforts to optimize the delivery of IVT to all AIS patients nationwide.
Failure of Therapeutic Anticoagulation in COVID-19 Patients With Acute Ischemic Stroke. A Retrospective Multicenter Study
Authors: Janes Francesco , Gigli Gian Luigi , Kuris Fedra , Morassi Mauro , Costa Paolo , Nesi Lorenzo , Giacomello Roberta , Mazzacane Federico , Leuci Eleonora , Cavallini Anna , Valente Mariarosaria
Published: March 2022

Background

Acute ischemic stroke (AIS) is a possible complication of coronavirus disease 2019 (COVID-19) infection. Although peculiar clinical features and underlying specific mechanisms of thrombogenesis have been suggested so far, there is no consensus on the appropriate vascular preventive drug regimen in patients with COVID-19.

Aim and Methods

From a larger clinical series of consecutive acute ischemic strokes related to COVID-19 admitted to three cerebrovascular units in Northern Italy, herein, we describe the clinical features of a subgroup of patients in whom stroke occurred despite therapeutic anticoagulation.

Results

A total of seventeen/80 AIS related to COVID-19 (21.2%) occurred in anticoagulated patients. Although no blood level was available for Direct Oral AntiCoagulant, the drug dosage was appropriate according to guidelines. Their National Institute of Health Stroke Scale (NIHSS) at admission was 12.0 (SD = 7.4) and 58.8% of them had evidence of large vessel occlusion. The case fatality rate was as high as 64.7%.

Discussion and Conclusions

The occurrence of an anticoagulation failure seems to be increased in the setting of COVID-19 infection, with worse clinical outcomes if compared to non-COVID-19 related ischemic strokes. We discuss the diagnostic and therapeutic implications of such evidence, suggesting that some arterial thrombotic complications might be either resistant to or independent of the anticoagulation effect.
Early Health Economic Modeling of Novel Therapeutics in Age-Related Hearing Loss
Authors: Landry Evie C. , Scholte Mirre , Su Matthew P. , Horstink Yvette , Mandavia Rishi , Rovers Maroeska M. , Schilder Anne G. M.
Published: March 2022

Background

Health systems face challenges to accelerate access to innovations that add value and avoid those unlikely to do so. This is very timely to the field of age-related sensorineural hearing loss (ARHL), where a significant unmet market need has been identified and sizeable investments made to promote the development of novel hearing therapeutics (NT). This study aims to apply health economic modeling to inform the development of cost-effective NT.

Methods

We developed a decision-analytic model to assess the potential costs and effects of using regenerative NT in patients ≥50 with ARHL. This was compared to the current standard of care including hearing aids and cochlear implants. Input data was collected from systematic literature searches and expert opinion. A UK NHS healthcare perspective was adopted. Three different but related analyses were performed using probabilistic modeling: (1) headroom analysis, (2) scenario analyses, and (3) threshold analyses.

Results

The headroom analysis shows an incremental net monetary benefit (iNMB) of £20,017[£11,299–£28,737] compared to the standard of care due to quality-adjusted life-years (QALY) gains and cost savings. Higher therapeutic efficacy and access for patients with all degrees of hearing loss yields higher iNMBs. Threshold analyses shows that the ceiling price of the therapeutic increases with more severe degrees of hearing loss.

Conclusion

NT for ARHL are potentially cost-effective under current willingness-to-pay (WTP) thresholds with considerable room for improvement in the current standard of care pathway. Our model can be used to help decision makers decide which therapeutics represent value for money and are worth commissioning, thereby paving the way for urgently needed NT.
Carpal Tunnel Syndrome and Ulnar Nerve Entrapment at the Elbow Are Not Associated With Plasma Levels of Caspase-3, Caspase-8 or HSP27
Authors: Bergsten Elin , Rydberg Mattias , Dahlin Lars B. , Zimmerman Malin
Published: March 2022

Background

Nerve compression disorders, such as carpal tunnel syndrome (CTS) and ulnar entrapment at the elbow (UNE), may be associated with apoptosis and neuroprotective mechanisms in the peripheral nerve that may be detected by biomarkers in the blood. The relationships between CTS and UNE and two biomarkers of apoptosis, i.e., caspase-3 and caspase-8, and the neuroprotective factor Heat Shock Protein 27 (HSP27) in plasma were examined in a population-based cohort.

Method

The biomarkers caspase-3, caspase-8 and HSP27 were measured in plasma at inclusion of 4,284 study participants aged 46–68 years in the population-based Malmö Diet and Cancer study (MDCS). End-point retrieval was made from national registers concerning CTS and UNE. Independent t-test was used to examine the association between caspase-3, caspase-8 and HSP27 plasma levels and incidence of CTS and UNE. Cox proportional hazards regression was used to investigate if plasma levels of caspase-3, caspase-8 and HSP27 affected time to diagnosis of CTS or UNE.

Results

During the mean follow-up time of 22 years, 189/4,284 (4%) participants were diagnosed with CTS and 42/4,284 (1%) were diagnosed with UNE. No associations were found between incident CTS or UNE and the biomarkers caspase-3, caspase-8 and HSP27 in plasma.

Conclusion

The apoptotic biomarkers caspase-3 and caspase-8 and the neuroprotective factor HSP27 in plasma, factors conceivably related to a nerve injury, are not associated with the nerve compression disorders CTS and UNE in a general population.