bluuebunny/crossref_metadata_2025 huggingface dataset:
EZH2 Inhibition Compromises α4-1BB-Mediated Antitumor Efficacy by Reducing the Survival and Effector Programming of CD8+ T Cells
Authors: Stairiker Christopher J. , Pfister Sophia Xiao , Hendrickson Eleanore , Yang Wenjing , Xie Tao , Lee Catherine , Zhang Haikuo , Dillon Christopher , Thomas Graham D. , Salek-Ardakani Shahram
Published: November 2021

Enhancer of Zeste Homolog 2 (EZH2) inhibitors (EZH2i) are approved to treat certain cancer types. Previous studies have suggested the potential to combine EZH2i with immune checkpoint blockade targeting coinhibitory receptors like PD-(L)1 and CTLA-4, but whether it can also enhance the activity of agents targeting costimulatory receptors is not known. Here, we explore the combination between EZH2i and an agonist antibody targeting the T cell costimulatory receptor 4-1BB (α4-1BB). Our data show that EZH2i compromise the efficacy of α4-1BB in both CT26 colon carcinoma and in an in vivo protein immunization model. We link this to reduced effector survival and increased BIM expression in CD8+ T cells upon EZH2i treatment. These data support the requirement of EZH2 function in 4-1BB-mediated CD8+ T cell expansion and effector programming and emphasize the consideration that must be given when combining such antitumoral therapies.
Effects of Dietary Mannan Oligosaccharides on Non-Specific Immunity, Intestinal Health, and Antibiotic Resistance Genes in Pacific White Shrimp Litopenaeus vannamei
Authors: Wang Tiantian , Yang Jinzhu , Lin Gang , Li Mingzhu , Zhu Ronghua , Zhang Yanjiao , Mai Kangsen
Published: November 2021

This study was conducted to comprehensively investigate the beneficial effects of a mannan oligosaccharide product (hereinafter called MOS) on Litopenaeus vannamei and optimum level of MOS. Five isonitrogenous and isolipid diets were formulated by adding 0%, 0.02%, 0.04%, 0.08%, and 0.16% MOS in the basal diet. Each diet was randomly fed to one group with four replicates of shrimp in an 8-week feeding trial. The results showed that dietary MOS improved the growth performance and the ability of digestion of shrimp. Dietary MOS significantly increased the activity of total superoxide dismutase, catalase, and glutathione peroxidase and decreased the content of malondialdehyde in plasma of shrimp. Dietary MOS significantly increased the activity of alkaline phosphatase and lysozyme in plasma and the hemocyte counts. Dietary MOS significantly upregulated the expression of Toll, lysozyme, anti-lipopolysaccharide factor, Crustin, and heat shock protein 70 in the hepatopancreas. And dietary MOS significantly upregulated the expression of intestinal mucin-2, mucin-5B, and mucin-19, while it decreased the expression of intestinal mucin-1 and macrophage migration inhibitory factor. Dietary MOS improved the bacterial diversity; increased the abundance of Lactobacillus, Bifidobacterium, Blautia, and Pseudoalteromonas; and decreased the abundance of Vibrio in the intestine. Shrimp fed MOS diets showed lower mortality after being challenged by Vibrio parahaemolyticus. Notably, this study found a decrease in antibiotic resistance genes and mobile genetic elements after MOS supplementation for the first time. The present results showed that diet with MOS supplementation enhanced the organismal antioxidant capacity and immunity, improved intestinal immunity, optimized intestinal microecology, mitigated the degree of antibiotic resistance, and increased the resistance to V. parahaemolyticus in L. vannamei, especially when supplemented at 0.08% and 0.16%.
Immune Cell Infiltration Analysis Demonstrates Excessive Mast Cell Activation in Psoriasis
Authors: Zhang Yongjun , Shi Yanqiang , Lin Jingxia , Li Xuefei , Yang Bin , Zhou Jiajian
Published: November 2021

Psoriasis represents multiple inflammatory processes and exaggerated physiological responses to epithelial damage by innate and adaptive immune components, thus it is critical to compare the immune cell niche in disease and healthy skin. Here, we inferred the proportions of different immune cell types in psoriatic and healthy skin using the CIBERSORT algorithm with expression profiles as input. As a result, we observed a dramatic change of immune cell profiles in psoriatic skin compared with healthy skin. Interestingly, the resting mast cells is almost eliminated in psoriatic skin. In contrast, the activated mast cells are enriched in psoriatic skin, indicating that mast cells activation may play an important role in psoriasis pathogenesis. In addition, we found that the proportion of the resting mast cells gradually come back to the normal level in lesioned skin upon etanercept treatment, suggesting that mast cells play a critical role in immune cell niche maintenance. Further experiments validated a significant decrease in mast cell population and an excessive mast cell activation in psoriatic skin compared with healthy skin. In conclusion, our integrative analyses of the immune cell profiles and the corresponding marker genes expression provide a better understanding of the inflammation response in psoriasis and important clues for clinical applications.
Increased Ratio of CD14++CD80+ Cells/CD14++CD163+ Cells in the Infrapatellar Fat Pad of End-Stage Arthropathy Patients
Authors: Ma Shuhe , Murakami Kosaku , Saito Rintaro , Ito Hiromu , Murata Koichi , Nishitani Kohei , Hashimoto Motomu , Tanaka Masao , Taniguchi Masahi , Kitagori Koji , Akizuki Shuji , Nakashima Ran , Yoshifuji Hajime , Ohmura Koichiro , Morinobu Akio , Mimori Tsuneyo
Published: December 2021

Objectives

This study sought to identify the ratio of M1/M2 cells in the infrapatellar fat pads (IFP) and subcutaneous fat tissues (SC) of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. The clinical features of OA and RA patients treated with or without biological disease-modifying anti-rheumatic drugs (bDMARDs) were also assessed.

Methods

IFP and SC were collected from patients with OA and RA who are undergoing total knee arthroplasty (TKA). CD14-positive cells were then isolated from these samples. Flow cytometry was used to determine the number of CD14++CD80+ cells and CD14++CD163+ cells. The expression levels of lipid transcription factors, such as sterol regulatory element-binding protein 1 (SREBP1) and liver X receptor alpha (LXRA), and inflammatory cytokines were also evaluated.

Results

Twenty OA patients and 22 RA patients were enrolled in this study. Ten of the RA patients (45.4%) received bDAMRDs before TKA. On average, a fivefold increase in the number of CD14-positive cells and lower expression levels of SREBP1C and LXRA were observed in OA IFP relative to OA SC; however, these results were not obtained from the RA samples. The median ratio of CD14++CD80+ cells/CD14++CD163+ cells of OA IFP was 0.87 (0.76–1.09, interquartile range), which is higher to that of OA SC with a lower ratio (p = 0.05835).

Conclusions

The quantity and quality of CD14-positive cells differed between IFP and SC in arthropathy patients. To our knowledge, this is the first study to characterize the ratio of M1/M2 cells in the IFP and SC of end-stage OA and RA patients. The increased ratio of CD14++CD80+ cells/CD14++CD163+ cells in the IFP from patients with OA and RA treated with bDMARDs indicated that inflammation was localized in the IFP. As adipose tissue-derived innate immune cells were revealed as one of the targets for regulating inflammation, further analysis of these cells in the IFP may reveal new therapeutic strategies for inflammatory joint diseases.
Subunit-Specific Reactivity of Autoantibodies Against Laminin-332 Reveals Direct Inflammatory Mechanisms on Keratinocytes
Authors: Bao Lei , Li Jing , Solimani Farzan , Didona Dario , Patel Payal M. , Li Xiaoguang , Qian Hua , Ishii Norito , Hashimoto Takashi , Hertl Michael , Amber Kyle T.
Published: November 2021

Laminin-332 pemphigoid is a rare and severe autoimmune blistering disease, caused by IgG autoantibodies targeting laminin-332 in the dermal-epidermal basement zone. Laminin-332 pemphigoid is characterized by variable inflammatory infiltrate and the predominance of non-complement-fixing antibodies. Given these findings, we hypothesized that IgG autoantibodies to laminin-332 directly resulted in keratinocyte expression of inflammatory factors. We performed RNA-seq on primary human keratinocytes treated with IgG from patients with laminin-332 pemphigoid. Genes for numerous cytokines and chemokines were upregulated, including CSF2, CSF3, CXCL1, CXCL5, CXCL3, CXCL8, CXCL10, CXCL1, IL6, IL7, IL15, IL23, IL32, IL37, TGFB2 as well as metalloproteases. Considering the pro-inflammatory and proteolytic effect of autoantibodies from patients with laminin-332 pemphigoid identified in our initial experiment, we next questioned whether the reactivity against specific laminin subunits dictates the inflammatory and proteolytic keratinocyte response. Then, we treated keratinocytes with IgG from a separate cohort of patients with reactivity against individual subunits of laminin-332. We identified upregulation of IL-1α, IL-6, IL-8, CXCL1, MMP9, TSLP, and GM-CSF at the protein level, most notably in keratinocytes treated with IgG from laminin β3-reactive patients. We for the first time demonstrated a pro-inflammatory response, similar to that described in keratinocytes treated with IgG autoantibodies from patients with bullous pemphigoid, providing novel insight into the pathogenesis of laminin-332 pemphigoid and laminin-332 biology.
Monomeric IgA Antagonizes IgG-Mediated Enhancement of DENV Infection
Authors: Wegman Adam D. , Fang Hengsheng , Rothman Alan L. , Thomas Stephen J. , Endy Timothy P. , McCracken Michael K. , Currier Jeffrey R. , Friberg Heather , Gromowski Gregory D. , Waickman Adam T.
Published: November 2021

Dengue virus (DENV) is a prevalent human pathogen, infecting approximately 400 million individuals per year and causing symptomatic disease in approximately 100 million. A distinct feature of dengue is the increased risk for severe disease in some individuals with preexisting DENV-specific immunity. One proposed mechanism for this phenomenon is antibody-dependent enhancement (ADE), in which poorly-neutralizing IgG antibodies from a prior infection opsonize DENV to increase infection of Fcgamma receptor-bearing cells. While IgM and IgG are the most commonly studied DENV-reactive antibody isotypes, our group and others have described the induction of DENV-specific serum IgA responses during dengue. We hypothesized that monomeric IgA would be able to neutralize DENV without the possibility of ADE. To test this, we synthesized IgG and IgA versions of two different DENV-reactive monoclonal antibodies. We demonstrate that isotype-switching does not affect the antigen binding and neutralization properties of the two mAbs. We show that DENV-reactive IgG, but not IgA, mediates ADE in Fcgamma receptor-positive K562 cells. Furthermore, we show that IgA potently antagonizes the ADE activity of IgG. These results suggest that levels of DENV-reactive IgA induced by DENV infection might regulate the overall IgG mediated ADE activity of DENV-immune plasmain vivo, and may serve as a predictor of disease risk.
Interaction Between Macrophage Extracellular Traps and Colon Cancer Cells Promotes Colon Cancer Invasion and Correlates With Unfavorable Prognosis
Authors: Chen Tianli , Wang Yue , Nan Zhaodi , Wu Jie , Li Ailu , Zhang Tingguo , Qu Xun , Li Chen
Published: December 2021

Background

Macrophage extracellular traps (METs) and tumor-infiltrating macrophages contribute to the progression of several diseases. But the role of METs and tumor-infiltrating macrophages in colon cancer (CC) has not been illuminated. In this study, we aimed to clarify the prognostic value of METs for CC patients and to explore the interaction between CC cells and METs in vitro and in vivo.

Methods

A training cohort consisting of 116 patients and a validation cohort of 94 patients were enrolled in this study. Immunofluorescence (IF) staining was conducted to determine METs formation in CC patients. Cox regression was used to perform prognostic analysis and screen out the best prognostic model. A nomogram was established to predict 5-year overall survival (OS). The correlation between METs with clinicopathological features and inflammatory markers was analyzed. The formation of METs in vitro was detected by SYTOX® green and IF staining, and the effect of METs on CC cells was detected by transwell assays. PAD2-IN-1, a selective inhibitor of peptidylarginine deiminase 2 (PAD2), was introduced to destroy the crosstalk between CC cells and METs in vitro and in vivo.

Results

METs levels were higher in CC tissues and were an independent prognostic factor for CC patients. The prognostic model consisting of age, tumors local invasion, lymph node metastasis and METs were confirmed to be consistent and accurate for predicting the 5-year OS of CC patients. Besides, METs were correlated with distant metastasis and inflammation. Through in vitro experiments, we confirmed that there was a positive feedback loop between CC cells and METs, in that METs promoted the invasion of CC cells and CC cells enhanced the production of METs, in turn. This interaction could be blocked by PAD2-IN-1 inhibitors. More importantly, animal experiments revealed that PAD2-IN-1 inhibited METs formation and CC liver metastasis in vivo.

Conclusions

METs were the potential biomarker of CC patient prognosis. PAD2-IN-1 inhibited the crosstalk between CC cells and METs in vitro and in vivo, which should be emphasized in CC therapy.
Purinergic Signaling in the Regulation of Gout Flare and Resolution
Authors: Li Xiaoling , Gao Jie , Tao Jinhui
Published: December 2021

Gout flares require monosodium urate (MSU) to activate the NLRP3 inflammasome and secrete sufficient IL-1β. However, MSU alone is not sufficient to cause a flare. This is supported by the evidence that most patients with hyperuricemia do not develop gout throughout their lives. Recent studies have shown that, besides MSU, various purine metabolites, including adenosine triphosphate, adenosine diphosphate, and adenosine bind to different purine receptors for regulating IL-1β secretion implicated in the pathogenesis of gout flares. Purine metabolites such as adenosine triphosphate mainly activate the NLRP3 inflammasome through P2X ion channel receptors, which stimulates IL-1β secretion and induces gout flares, while some purine metabolites such as adenosine diphosphate and adenosine mainly act on the G protein-coupled receptors exerting pro-inflammatory or anti-inflammatory effects to regulate the onset and resolution of a gout flare. Given that the purine signaling pathway exerts different regulatory effects on inflammation and that, during the inflammatory process of a gout flare, an altered expression of purine metabolites and their receptors was observed in response to the changes in the internal environment. Thus, the purine signaling pathway is involved in regulating gout flare and resolution. This study was conducted to review and elucidate the role of various purine metabolites and purinergic receptors during the process.
Myeloid Protease-Activated Receptor-2 Contributes to Influenza A Virus Pathology in Mice
Authors: Gunther Randall C. , Bharathi Vanthana , Miles Stephen D. , Tumey Lauryn R. , Schmedes Clare M. , Tatsumi Kohei , Bridges Meagan D. , Martinez David , Montgomery Stephanie A. , Beck Melinda A. , Camerer Eric , Mackman Nigel , Antoniak Silvio
Published: December 2021

Background

Innate immune responses to influenza A virus (IAV) infection are initiated in part by toll-like receptor 3 (TLR3). TLR3-dependent signaling induces an antiviral immune response and an NFκB-dependent inflammatory response. Protease-activated receptor 2 (PAR2) inhibits the antiviral response and enhances the inflammatory response. PAR2 deficiency protected mice during IAV infection. However, the PAR2 expressing cell-types contributing to IAV pathology in mice and the mechanism by which PAR2 contributes to IAV infection is unknown.

Methods

IAV infection was analyzed in global (Par2-/-), myeloid (Par2fl/fl;LysMCre+) and lung epithelial cell (EpC) Par2 deficient (Par2fl/fl;SPCCre+) mice and their respective controls (Par2+/+ and Par2fl/fl). In addition, the effect of PAR2 activation on polyinosinic-polycytidylic acid (poly I:C) activation of TLR3 was analyzed in bone marrow-derived macrophages (BMDM). Lastly, we determined the effect of PAR2 inhibition in wild-type (WT) mice.

Results

After IAV infection, Par2-/- and mice with myeloid Par2 deficiency exhibited increased survival compared to infected controls. The improved survival was associated with reduced proinflammatory mediators and reduced cellular infiltration in bronchoalveolar lavage fluid (BALF) of Par2-/- and Par2fl/fl;LysMCre+ 3 days post infection (dpi) compared to infected control mice. Interestingly, Par2fl/fl;SPCCre+ mice showed no survival benefit compared to Par2fl/fl. In vitro studies showed that Par2-/- BMDM produced less IL6 and IL12p40 than Par2+/+ BMDM after poly I:C stimulation. In addition, activation of PAR2 on Par2+/+ BMDM increased poly I:C induction of IL6 and IL12p40 compared to poly I:C stimulation alone. Importantly, PAR2 inhibition prior to IAV infection protect WT mice.

Conclusion

Global Par2 or myeloid cell but not lung EpC Par2 deficiency was associated with reduced BALF inflammatory markers and reduced IAV-induced mortality. Our study suggests that PAR2 may be a therapeutic target to reduce IAV pathology.
Complement Mediated Hemolytic Anemias in the COVID-19 Era: Case Series and Review of the Literature
Authors: Fattizzo Bruno , Pasquale Raffaella , Bellani Valentina , Barcellini Wilma , Kulasekararaj Austin G.
Published: November 2021

The complex pathophysiologic interplay between SARS-CoV-2 infection and complement activation is the subject of active investigation. It is clinically mirrored by the occurrence of exacerbations of complement mediated diseases during COVID-19 infection. These include complement-mediated hemolytic anemias such as paroxysmal nocturnal hemoglobinuria (PNH), autoimmune hemolytic anemia (AIHA), particularly cold agglutinin disease (CAD), and hemolytic uremic syndrome (HUS). All these conditions may benefit from complement inhibitors that are also under study for COVID-19 disease. Hemolytic exacerbations in these conditions may occur upon several triggers including infections and vaccines and may require transfusions, treatment with complement inhibitors and/or immunosuppressors (i.e., steroids and rituximab for AIHA), and result in thrombotic complications. In this manuscript we describe four patients (2 with PNH and 2 with CAD) who experienced hemolytic flares after either COVID-19 infection or SARS-Cov2 vaccine and provide a review of the most recent literature. We report that most episodes occurred within the first 10 days after COVID-19 infection/vaccination and suggest laboratory monitoring (Hb and LDH levels) in that period. Moreover, in our experience and in the literature, hemolytic exacerbations occurring during COVID-19 infection were more severe, required greater therapeutic intervention, and carried more complications including fatalities, as compared to those developing after SARS-CoV-2 vaccine, suggesting the importance of vaccinating this patient population. Patient education remains pivotal to promptly recognize signs/symptoms of hemolytic flares and to refer to medical attention. Treatment choice should be based on the severity of the hemolytic exacerbation as well as of that of COVID-19 infection. Therapies include transfusions, complement inhibitor initiation/additional dose in the case of PNH, steroids/rituximab in patients with CAD and warm type AIHA, plasma exchange, hemodialysis and complement inhibitor in the case of atypical HUS. Finally, anti-thrombotic prophylaxis should be always considered in these settings, provided safe platelet counts.
The HSP Immune Network in Cancer
Authors: Albakova Zarema , Mangasarova Yana
Published: December 2021

Heat shock proteins are molecular chaperones which support tumor development by regulating various cellular processes including unfolded protein response, mitochondrial bioenergetics, apoptosis, autophagy, necroptosis, lipid metabolism, angiogenesis, cancer cell stemness, epithelial-mesenchymal transition and tumor immunity. Apart from their intracellular activities, HSPs have also distinct extracellular functions. However, the role that HSP chaperones play in the regulation of immune responses inside and outside the cell is not yet clear. Herein, we explore the intracellular and extracellular immunologic functions of HSPs in cancer. A broader understanding of how HSPs modulate immune responses may provide critical insights for the development of effective immunotherapies.
The HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B*07:02
Authors: Mukherjee Soumya , Sanchez-Bernabeu Alvaro , Demmers Laura C. , Wu Wei , Heck Albert J. R.
Published: December 2021

Mass-spectrometry based immunopeptidomics has provided unprecedented insights into antigen presentation, not only charting an enormous ligandome of self-antigens, but also cancer neoantigens and peptide antigens harbouring post-translational modifications. Here we concentrate on the latter, focusing on the small subset of HLA Class I peptides (less than 1%) that has been observed to be post-translationally modified (PTM) by a O-linked N-acetylglucosamine (GlcNAc). Just like neoantigens these modified antigens may have specific immunomodulatory functions. Here we compiled from literature, and a new dataset originating from the JY B cell lymphoblastoid cell line, a concise albeit comprehensive list of O-GlcNAcylated HLA class I peptides. This cumulative list of O-GlcNAcylated HLA peptides were derived from normal and cancerous origin, as well as tissue specimen. Remarkably, the overlap in detected O-GlcNAcylated HLA peptides as well as their source proteins is strikingly high. Most of the O-GlcNAcylated HLA peptides originate from nuclear proteins, notably transcription factors. From this list, we extract that O-GlcNAcylated HLA Class I peptides are preferentially presented by the HLA-B*07:02 allele. This allele loads peptides with a Proline residue anchor at position 2, and features a binding groove that can accommodate well the recently proposed consensus sequence for O-GlcNAcylation, P(V/A/T/S)g(S/T), essentially explaining why HLA-B*07:02 is a favoured binding allele. The observations drawn from the compiled list, may assist in the prediction of novel O-GlcNAcylated HLA antigens, which will be best presented by patients harbouring HLA-B*07:02 or related alleles that use Proline as anchoring residue.
Impact of Freshwater Discharge on the Carbon Uptake Rate of Phytoplankton During Summer (January–February 2019) in Marian Cove, King George Island, Antarctica
Authors: Kim Bo Kyung , Jeon Misa , Joo Hyoung Min , Kim Tae-Wan , Park Sang-Jong , Park Jisoo , Ha Sun-Yong
Published: November 2021

Rapidly changing conditions in high-latitude coastal systems can significantly impact biogeochemical cycles because these systems are strongly influenced by freshwater discharged from melting glaciers and streams on land. Generally, Antarctic coastal areas are considered high-productivity areas in which phytoplankton growth prevails under various environmental conditions (e.g., oceanographic and meteorological conditions). This study provides carbon uptake rates of phytoplankton in Marian Cove during summer (January-February 2019). Daily depth-integrated carbon uptake varied greatly and averaged 0.8 g C m–2 day–1, with a maximum of 4.52 mg g C m–2 day–1 recorded on 14 January. Similarly, the observed biomass standing stocks were very high (up to 19.5 mg m–3 chlorophyll a) and were dominated by microphytoplankton (20–200 μm), representing 84% of total chlorophyll a (chl-a). The depth-integrated chl-a and carbon uptake decreased from outer to inner areas (close to the glacial front) in the cove. As the austral summer progressed, the freshening of the surface waters coincided with high water stability and suspended material and with low productivity when nanophytoplankton were present (2–20 μm; >60%). These findings suggest that both photosynthetically active radiation penetrating the water column and enhanced turbidity control light availability for phytoplankton, as well as their community compositions.
Influence of Light/Dark Cycles on Body Color, Hepatopancreas Metabolism, and Intestinal Microbiota Homeostasis in Litopenaeus vannamei
Authors: Jiao Lefei , Dai Tianmeng , Tao Xinyue , Lu Jingjing , Zhou Qicun
Published: December 2021

In aquatic animals, the light/dark cycle acts as an important biological factor that influences the entire life cycle. Until present, evidence regarding the regulation of physiological metabolic process under different light/dark cycles is limited in Litopenaeus vannamei. In this study, we mainly investigated the effects of different light/dark cycles (12 h light/12 h dark, 0 h light/24 h dark) on the hepatopancreas metabolism and intestinal microbiota homeostasis in L. vannamei using multiomics techniques. One interesting finding was that the body color of L. vannamei became darker after dark treatment for 8 weeks. Further hepatopancreas transcriptome analysis identified down-regulated genes involved in regulating nutrition metabolism, body-color formation, diurnal rhythm, immune function, hormone levels, and posttranslational modifications. The intestinal microbiota analysis showed that dark treatment-induced alterations in intestinal bacterial abundances in L. vannamei, such as decreased (P < 0.05) relative abundance of Formosa, Demequina, Lutimonas and increased (P < 0.05) relative abundance of Ruegeria, Vibrio, Actibacter, Roseovarius, Ilumatobacter, and Kriegella at the genus level. The microbiota functional analysis demonstrated that the dark treatment mainly increased susceptibility of pathogens, decreased nutrition metabolism, and influenced circadian rhythm. This study indicated for the first time that constant darkness treatment darkened the body color and altered hepatopancreas metabolism and intestinal microbiota homeostasis in L. vannamei, which might give potential clues for improving the productive capacities by changing light/dark cycles in shrimp farming.
Satellite Tracking of Post-nesting Green Sea Turtles (Chelonia mydas) From Ras Baridi, Red Sea
Authors: Al-Mansi Ahmed M. , Sambas Anas Z. , Abukaboos Baleegh A. , Al Zahrani Ahmed H. , Abdulaziz Ahmed S. , Almasabi Ali A. , Alkreda Raed S. , Miller Jeff
Published: December 2021

Identifying migratory pathways and linking nesting sites to foraging areas is essential for effective conservation management of migratory species, such as marine turtles. Post-nesting marine turtles disperse from their nesting sites to multiple foraging areas located from a few to hundreds of kilometers away. Over a six-year period 16 female green turtles (Chelonia mydas) were equipped with satellite transmitters between October and December of five nesting seasons to determine their migratory routes from their nesting area at five contiguous beaches at Ras Baridi, Saudi Arabia, to their foraging areas. All foraging areas for these turtles were located in shallow coastal areas or in shallow areas around offshore islands within the Red Sea basin. The majority (n = 12) migrated through the shallow (<200 m) water along the coastal margin to reach foraging areas located to the North (n = 4) and South (n = 12) of the nesting site. Four turtles crossed the deep trough of the Red Sea during their journeys. Ten of the 16 turtles migrated to foraging areas within the territorial waters of Saudi Arabia. The other six turtles migrated to foraging areas in Egypt (n = 4) and Eritrea (n = 2). These 16 turtles traveled between 130 and 1749 km from their nesting site to foraging areas located in the northern, middle and southern parts of the Red Sea. Because these turtles utilized foraging areas in at least three countries (Saudi Arabia, Egypt, and Eritrea) and one passed through the territorial waters of Sudan, conservation and management of green turtles in the Red Sea requires multinational cooperation to address anthropogenic threats in the region.
Is the South-Mediterranean Canopy-Forming Ericaria giacconei (= Cystoseira hyblaea) a Loser From Ocean Warming?
Authors: Falace Annalisa , Marletta Giuliana , Savonitto Gilda , Candotto Carniel Fabio , Srijemsi Marina , Bevilacqua Stanislao , Tretiach Mauro , Alongi Giuseppina
Published: November 2021

Canopy-forming brown algae support highly productive ecosystems whose decline has been attributed to the interplay of several anthropogenic disturbances. Climate change could have disruptive effects on the biology of these species, but the role of temperature in the development of early life stages is poorly understood. The aim of this study was to assess the response of Ericaria giacconei, a winter-reproducing Southern–Mediterranean endemic species, to thermal stress by testing five temperatures (12, 15, 18, 24, and 28°C) on adults and early stages. Chlorophyll a fluorescence of adult plants was measured at 0, 24, 72, and 120 h on nine fronds in each of the three aquaria per treatment. To assess egg release, zygote settlement, and embryo growth rate, approximately 1,200 receptacles were cultured on six Petri dishes per temperature treatment, and 10 random subsections of 2 ×2 mm were examined in three Petri dishes at 0, 20, 44, and 92 h after fertilization. Adult plants showed a plastic physiological response, and thermal stress had no significant effect on PSII efficiency. Embryos fully developed only at 12 and 15°C. Mortality increased at 18 and 24°C, and no zygotes survived at 28°C. In a scenario of further increasing temperatures, the effects of warming could affect the recruitment of E. giacconei and increase its vulnerability to further stresses. These effects on the survival of early stages, which are the bottleneck for the long-term survival of the species, should be taken into account in conservation and restoration measures to maintain canopy-forming macroalgal populations and associated biodiversity and ecosystem services.
Evaluating the Effects of a Deep-Water Marine Protected Area a Decade After Closure: A Multifaceted Approach Reveals Equivocal Benefits to Reef Fish Populations
Authors: Runde Brendan J. , Buckel Jeffrey A. , Rudershausen Paul J. , Mitchell Warren A. , Ebert Erik , Cao Jie , Taylor J. Christopher
Published: November 2021

Marine protected areas (MPAs) are increasingly used to rebuild fish populations. In 2009, eight MPAs were designated off the southeast United States with the goal of rebuilding populations of long-lived deep-water reef fishes. We tested whether reef fish within the largest of these MPAs, the Snowy Wreck Marine Protected Area (SWMPA), have increased in size and abundance relative to a nearby control area and compared to pre-closure. Hurdle models fitted through Bayesian inference on echosounder data collected in 2007–2009 and 2018–2020 yielded no evidence of an MPA effect. Comparisons of catch-per-unit-effort (CPUE) of all reef fishes yielded similar null results. However, CPUE of reef species with formal stock assessments increased 47% in the SWMPA and decreased 50% in the control area. We found significant increases in mean length of red porgy (Pagrus pagrus) inside the SWMPA but not in the control area. We also found community composition changes, including shifts away from groupers (Serranidae; Epinephelinae) and toward snappers (Lutjanidae) and tilefish (Malacanthidae) in both areas, though we did not detect an MPA effect with this analysis. Our equivocal results indicate that more time and stricter enforcement may be necessary before more biological effects of the SWMPA can be detected.
The Effect of Oxidized Fish Oil on the Spleen Index, Antioxidant Activity, Histology and Transcriptome in Juvenile Hybrid Grouper (♀ Epinephelus fuscoguttatus × ♂ Epinephelus lanceolatus)
Authors: Long Shuisheng , Li Zhihao , Dong Xiaohui , Yan Xiaobo , Liu Hao , Tan Beiping , Zhang Shuang , Pan Simiao , Li Tao , Suo Xiangxiang , Yang Yuanzhi
Published: November 2021

The spleen is an important organ in the immune function of fish, and it is also important for hematogenesis and antibody and granulocyte production. However, the effect of oxidized fish oil on the spleen of hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ Epinephelus lanceolatus) is unknown. In this study, hybrid groupers were fed with oxidized fish oil and the spleen index, antioxidant ability, histology and transcriptome were investigated. Oxidized fish oil did not affect the spleen index. Levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in the spleen were significantly increased as the amount of oxidized fish oil in the diet increased, but the vitamin E concentration was significantly decreased. The morphological organization of the spleen was damaged with increased oxidative stress. And the spleen reacted to oxidative stress by platelet activation, FOXO and notch signaling pathways, which involved amyloid beta precursor protein binding family B member 1 interacting protein (APBB1IP) gene, glucose-6-phosphatase (G6PC) gene, histone acetyltransferase p300 (EP300) gene, insulin gene and notch 2 gene. In conclusion, the oxidized fish oil caused oxidative stress and damaged its structure. Additionally, oxidized fish oil changed the transcription profile of the spleen.
Recent Advances in Spinel Ferrite-Based Thin Films: Synthesis, Performances, Applications, and Beyond
Authors: Hao Aize , Ning Xueer
Published: November 2021

This review provides a comprehensive overview of the recent advances in the various typical spinel ferrite-based thin films with controlled synthesis, their performances, applications in multifunctional material fields, fundamental scientific challenges, and beyond. Firstly, the crystal structures of spinel ferrite-based thin films are introduced. Secondly, recent progress in traditional synthesizing and novel methods for preparation of spinel ferrite-based films are highlighted. Thirdly, their magnetism, electricity, optics performances, and applications in advanced information technology, energy storage and conversion, and environmental conservation fields are also summarized and discussed in-depth. Some effective strategies for optimizing performances and further applications are summarized. Finally, the present review work ends with a short discussion concerning the challenges, opportunities, and future prospects of spinel ferrite-based thin films.
Experimental Study on Mechanical Performance of Recycled Fine Aggregate Concrete Reinforced With Discarded Carbon Fibers
Authors: Zaid Osama , Zamir Hashmi Syed Roshan
Published: November 2021

With the development of technology in every field, it is necessary to recommend an eco-friendly material to be utilized in the construction industry. Recently, using waste/recycled materials in the concrete as a substitute is a trend to bring sustainability to the construction industry, but the recycled/waste materials has poor mechanical properties, thus to enhance these poor properties, this research studies the mechanical performance of sustainable concrete incorporating waste materials as aggregates, the study is performed in the three stages. In the first stage, the natural sand was substituted with recycled sand in the percentage of 0, 35, 70, and 100%, and all the tests i.e. compressive strength, split tensile strength and flexural strength were performed on concrete which was cured in water for 28 days. As the 35% substitution of natural sand with recycled fine aggregate presented the optimum mechanical performance, it was selected for the third stage of the research. In the second and the third stages, the discarded carbon fibers were utilized in concrete with 2, 4, and 6% by weight. A total of 90 samples were prepared for this research, in which 30 samples were cubes, 30 samples were cylinders and 30 samples were beams, all the samples were tested at 28 days. Comparative analysis was performed to validate and verify the results of this paper with the relevant literature. The SEM test was also performed on a fractured concrete surface to study its microstructure. The outcome of tests revealed that the utilization of discarded carbon fibers in concrete enhances compressive, split tensile and flexural strength by 27.8, 17.8, and 35.9% and acts as a crack bridging and also restrain the propagation of the first cracks. Fibers also helped the concrete to improve its energy absorption capacity and ductility.
The Efficacy and Safety of Ultrasound-Guided, Bi-Level, Erector Spinae Plane Block With Different Doses of Dexmedetomidine for Patients Undergoing Video-Assisted Thoracic Surgery: A Randomized Controlled Trial
Authors: Gao Xiujuan , Zhao Tonghang , Xu Guangjun , Ren Chunguang , Liu Guoying , Du Ke
Published: November 2021

Background: The anesthetic characteristics of ultrasound-guided bi-level erector spinae plane block (ESPB) plus dexmedetomidine (Dex) remain unclear. We compared the efficacy and safety of ultrasound-guided bi-level ESPB plus different doses of Dex in patients undergoing video-assisted thoracic surgery (VATS).

Methods: One-hundred eight patients undergoing VATS were randomized into three groups: R group (n = 38, 15 ml of 0.375% ropivacaine with 0.1 mg/kg dexamethasone), RD1 group (n = 38, 15 ml of 0.375% ropivacaine plus 0.5 μg/kg DEX with 0.1 mg/kg dexamethasone) and RD2 group (n = 38, 15 ml of 0.375% ropivacaine plus 1.0 μg/kg DEX with 0.1 mg/kg dexamethasone). The primary outcome was the pain 12 h after surgery. Secondary outcomes included the Prince Henry Hospital Pain Score; hemodynamics; consumption of sufentanil; anesthetized dermatomal distribution; recovery time; rescue analgesia; satisfaction scores of patients and surgeon; quick recovery index; adverse effects; the prevalence of chronic pain and quality of recovery.

Results: The visual analog scale (VAS) and the Prince Henry pain score were significantly lower in both the RD1 and RD2 groups during the first 24 h after surgery (P
< 0.05). Both VAS with coughing and the Prince Henry pain score were significantly lower in the RD2 group than in the RD1 group 8–24 h after surgery (P < 0.05). Both heart rate and mean arterial pressure were significantly different from T2 to T6 in the RD1 and RD2 groups (P < 0.05). The receipt of remifentanil, propofol, Dex, and recovery time was significantly reduced in the RD2 group (P < 0.05). The requirement for sufentanil during the 8–72 h after surgery, less rescue medication, and total press times were significantly lower in the RD2 group (P < 0.05). The time to the first dose of rescue ketorolac was significantly longer in the RD2 group (P < 0.05). Further, anal exhaust, removal of chest tubes, and ambulation were significantly shorter in the RD2 group (P < 0.05). The incidence of tachycardia, post-operative nausea and vomiting, and chronic pain was significantly reduced in the RD2 group, while the QoR-40 score was significantly higher in the RD2 group (P < 0.05).

Conclusions: Pre-operative bi-level, single-injection ESPB plus 1 μg/kg DEX provided superior pain relief and long-term post-operative recovery for patients undergoing VATS.

Clinical Trial Registration:http://www.chictr.org.cn/searchproj.aspx.
Vaccine Hesitancy Is a Barrier to Achieving Equitable Herd Immunity Among Racial Minorities
Authors: Gerretsen Philip , Kim Julia , Quilty Lena , Wells Samantha , Brown Eric E. , Agic Branka , Pollock Bruce G. , Graff-Guerrero Ariel
Published: November 2021

Introduction:Racial minority groups have been disproportionately affected by the 2019 novel coronavirus disease (COVID-19). Vaccine hesitancy may be a major barrier to achieving equitable herd immunity and must be addressed to reduce the excess morbidity and mortality of COVID-19 in disproportionately affected communities. This study aimed to determine if COVID-19 vaccine hesitancy, and its factors vaccine complacency and confidence, are more prominent among disproportionately affected racial minority groups.

Methods:We collected data from participants aged 18 years or older from the four most populous U.S. states, including New York, California, Florida, and Texas, and Canada. Data were collected using a web-based survey platform. Data are available athttp://www.covid19-database.com.

Results:Data from 4,434 participants were included [mean (SD) age = 48.7 (17.2) and 50.4% women]. Vaccine hesitancy was higher in Black, Indigenous (Native American and Indigenous People of Canada, including First Nations, Inuit and Métis), and Latinx compared to White participants, while no difference was found between East Asian and White participants. The group differences in vaccine hesitancy for Indigenous and Black compared to White participants remained after controlling for sociodemographic factors. Determinants of vaccine complacency were equivalent between disproportionately affected racial groups and white participants. Vaccine confidence (i.e., trust in vaccine benefit) was generally lower in all racial groups compared to White participants. Differences in vaccine mistrust comparing Black and East Asian to White participants remained after controlling for sociodemographic factors.

Discussion:Disproportionately affected racial minorities may have higher vaccine hesitancy and lower confidence in COVID-19 vaccines. Public health and other relevant government services should address vaccine hesitancy among racial minorities using a culturally sensitive, community-centered approach to attain equitable herd immunity.
Bronchoscopy-Guided Intervention Therapy With Extracorporeal Membrane Oxygenation Support for Relapsing Polychondritis With Severe Tracheobronchomalacia: A Case Report and Literature Review
Authors: Zhou Pengcheng , Fu Bing , Zhang Chuantao , Chen Keling , Xia Qianming , Tang Wenjun , Yu Wei , Huang Wenhui
Published: November 2021

Relapsing polychondritis is an immune disorder of unknown etiology involving multiple systems that is characterized by persistent inflammation and destruction of cartilage, including the ears, nose, costal, joint, and airways. Airway involvement caused by relapsing polychondritis is common, and tracheobronchomalacia is the most serious complication, which is life-threatening. Currently, the exact mechanism of relapsing polychondritis with tracheobronchomalacia is unknown. Although glucocorticoids and immunosuppressive agents are administered, failures often occur. Currently, bronchoscopy-guided intervention therapy used in tracheobronchomalacia caused by chronic obstructive pulmonary disease or other etiology has gradually increased, but bronchoscopy-guided intervention therapy with extracorporeal membrane oxygenation assist used in tracheobronchomalacia caused by relapsing polychondritis has not been reported. Here, we report a case of relapsing polychondritis with severe tracheobronchomalacia. Although drug therapy was provided and airway stent implantation was performed, the tracheal stenosis was further aggravated. Because conventional anesthesia and mechanical ventilation cannot meet the needs of bronchoscopy-guided intervention therapy or guarantee sufficient safety. The intervention treatment was performed with the support of extracorporeal membrane oxygenation, which was successfully completed without obvious complications. The symptoms were significantly improved, and the patient was discharged uneventfully.
Neuroinflammation and Its Impact on the Pathogenesis of COVID-19
Authors: Almutairi Mohammed M. , Sivandzade Farzane , Albekairi Thamer H. , Alqahtani Faleh , Cucullo Luca
Published: November 2021

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.
Differential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue—Multi-omics Insights From the Munich MIDY Pig Model
Authors: Flenkenthaler Florian , Ländström Erik , Shashikadze Bachuki , Backman Mattias , Blutke Andreas , Philippou-Massier Julia , Renner Simone , Hrabe de Angelis Martin , Wanke Rüdiger , Blum Helmut , Arnold Georg J. , Wolf Eckhard , Fröhlich Thomas
Published: November 2021

Adipose tissue (AT) is no longer considered to be responsible for energy storage only but is now recognized as a major endocrine organ that is distributed across different parts of the body and is actively involved in regulatory processes controlling energy homeostasis. Moreover, AT plays a crucial role in the development of metabolic disease such as diabetes. Recent evidence has shown that adipokines have the ability to regulate blood glucose levels and improve metabolic homeostasis. While AT has been studied extensively in the context of type 2 diabetes, less is known about how different AT types are affected by absolute insulin deficiency in type 1 or permanent neonatal diabetes mellitus. Here, we analyzed visceral and subcutaneous AT in a diabetic, insulin-deficient pig model (MIDY) and wild-type (WT) littermate controls by RNA sequencing and quantitative proteomics. Multi-omics analysis indicates a depot-specific dysregulation of crucial metabolic pathways in MIDY AT samples. We identified key proteins involved in glucose uptake and downstream signaling, lipogenesis, lipolysis and β-oxidation to be differentially regulated between visceral and subcutaneous AT in response to insulin deficiency. Proteins related to glycogenolysis, pyruvate metabolism, TCA cycle and lipogenesis were increased in subcutaneous AT, whereas β-oxidation-related proteins were increased in visceral AT from MIDY pigs, pointing at a regionally different metabolic adaptation to master energy stress arising from diminished glucose utilization in MIDY AT. Chronic, absolute insulin deficiency and hyperglycemia revealed fat depot-specific signatures using multi-omics analysis. The generated datasets are a valuable resource for further comparative and translational studies in clinical diabetes research.