bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic performance of multiple biomarkers in patients with acute coronary syndrome without standard cardiovascular risk factors
Authors: Wang Le , Cong Hong-liang , Zhang Jing-xia , Li Xi-ming , Hu Yue-cheng , Wang Chen , Lang Jia-chun , Zhou Bing-yang , Li Ting-ting , Liu Chun-wei , Yang Hua , Ren Li-bin , Qi Wei , Li Wen-yu
Published: July 2022

Background and aims

Acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors (SMuRFs) represents a special case of ACS. Multiple biomarkers have been shown to improve risk stratification in patients with ACS. However, the utility of biomarkers for prognostic stratification in patients with ACS without SMuRFs remains uncertain. The aim of the present study was to evaluate the prognostic value of various biomarkers in patents with ACS without SMuRFs.

Methods

Data of consecutive patients with ACS without SMuRFs who underwent coronary angiography in Tianjin Chest Hospital between January 2014 and December 2017 were retrospectively collected. The primary outcome was the occurrence of major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, myocardial infarction and stroke. Seven candidate biomarkers analyses were analyzed using models adjusted for established risk factors.

Results

During a median 5-year follow-up, 81 of the 621 patients experienced a MACE. After adjustment for important covariates, elevated fibrinogen, D-dimer, N-terminal proB-type natriuretic peptide (NT-proBNP), and lipoprotein (a) [Lp(a)] were found to be individually associated with MACE. However, only D-dimer, NT-proBNP and Lp(a) significantly improved risk reclassification for MACE (all P < 0.05). The multimarker analysis showed that there was a clear increase in the risk of MACE with an increasing number of elevated biomarkers and a higher multimarker score. The adjusted hazard ratio- for MACE (95% confidential intervals) for patients with 4 elevated biomarkers was 6.008 (1.9650–18.367) relative to those without any elevated biomarker-. Adding- the 4 biomarkers or the multimarker score to the basic model significantly improved the C-statistic value, the net reclassification index and the integrated discrimination index (all P < 0.05).

Conclusion

Fibrinogen, D-dimer, NT-proBNP and Lp(a) provided valuable prognostic information for MACE when applied to patients with ACS without SMuRFs. The multimarker strategy, which combined multiple biomarkers reflecting different pathophysiological process with traditional risk factors improved the cardiovascular risk stratification.
Does the RGD region of certain proteins affect metabolic activity?
Authors: Nagasaki Karin , Gavrilova Oksana , Hajishengallis George , Somerman Martha J.
Published: July 2022

A better understanding of the role of mineralized tissues and their associated factors in governing whole-body metabolism should be of value toward informing clinical strategies to treat mineralized tissue and metabolic disorders, such as diabetes and obesity. This perspective provides evidence suggesting a role for the arginine-glycine-aspartic acid (RGD) region, a sequence identified in several proteins secreted by bone cells, as well as other cells, in modulating systemic metabolic activity. We focus on (a) two of the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family genes/proteins, bone sialoprotein (BSP) and osteopontin (OPN), (b) insulin-like growth factor-binding protein-1 & 2 (IGFBP-1, IGFBP-2) and (c) developmental endothelial locus 1 (DEL1) and milk fat globule–EGF factor-8 (MFG-E8). In addition, for our readers to appreciate the mounting evidence that a multitude of bone secreted factors affect the activity of other tissues, we provide a brief overview of other proteins, to include fibroblast growth factor 23 (FGF23), phosphatase orphan 1 (PHOSPHO1), osteocalcin (OCN/BGLAP), tissue non-specific alkaline phosphatase (TNAP) and acidic serine aspartic-rich MEPE-associated motif (ASARM), along with known/suggested functions of these factors in influencing energy metabolism.
Effects of Postural Education Program (PEPE Study) on Daily Habits in Children
Authors: Galmes-Panades Aina Maria , Vidal-Conti Josep
Published: July 2022

The current randomized controlled trial aimed to investigate the effects of a postural education program on daily life habits related to low back pain (LBP) in children. Reducing the disease burden of unspecific LBP in children is of major public health relevance, as children with episodes of LBP tend to experience chronic back pain in adulthood. The study was performed in Majorca (Spain), with 253 primary school children aged between 10 and 12 years. The sample was selected from different clusters (schools) using convenience sampling and randomly distributed into an experimental group (5 schools) or a control group (5 schools). Individual postural items did not improve after the intervention in the experimental group, nor did they improve in the control group. Neither did they improve postural habits score in both groups after the intervention. In conclusion, this telematic intervention has not managed to improve postural habits in children. Nevertheless, there is a lack of evidence to determine whether it is feasible to carry out telematics intervention that promotes lifestyle changes in children.
Adrenalectomies in children and adolescents in Germany – a diagnose related groups based analysis from 2009-2017
Authors: Uttinger Konstantin L. , Riedmeier Maria , Reibetanz Joachim , Meyer Thomas , Germer Christoph Thomas , Fassnacht Martin , Wiegering Armin , Wiegering Verena
Published: July 2022

Background

Adrenalectomies are rare procedures especially in childhood. So far, no large cohort study on this topic has been published with data on to age distribution, operative procedures, hospital volume and operative outcome.

Methods

This is a retrospective analysis of anonymized nationwide hospital billing data (DRG data, 2009-2017). All adrenal surgeries (defined by OPS codes) of patients between the age 0 and 21 years in Germany were included.

Results

A total of 523 patient records were identified. The mean age was 8.6 ± 7.7 years and 262 patients were female (50.1%). The majority of patients were between 0 and 5 years old (52% overall), while 11.1% were between 6 and 11 and 38.8% older than 12 years. The most common diagnoses were malignant neoplasms of the adrenal gland (56%, mostly neuroblastoma) with the majority being younger than 5 years. Benign neoplasms in the adrenal gland (D350) account for 29% of all cases with the majority of affected patients being 12 years or older. 15% were not defined regarding tumor behavior. Overall complication rate was 27% with a clear higher complication rate in resection for malignant neoplasia of the adrenal gland. Bleeding occurrence and transfusions are the main complications, followed by the necessary of relaparotomy. There was an uneven patient distribution between hospital tertiles (low volume, medium and high volume tertile). While 164 patients received surgery in 85 different “low volume” hospitals (0.2 cases per hospital per year), 205 patients received surgery in 8 different “high volume” hospitals (2.8 cases per hospital per year; p<0.001). Patients in high volume centers were significant younger, had more extended resections and more often malignant neoplasia. In multivariable analysis younger age, extended resections and open procedures were independent predictors for occurrence of postoperative complications.

Conclusion

Overall complication rate of adrenalectomies in the pediatric population in Germany is low, demonstrating good therapeutic quality. Our analysis revealed a very uneven distribution of patient volume among hospitals.
Genetic Basis of Sexual Maturation Heterosis: Insights From Ovary lncRNA and mRNA Repertoire in Chicken
Authors: Wang Yuanmei , Yuan Jingwei , Sun Yanyan , Li Yunlei , Wang Panlin , Shi Lei , Ni Aixin , Zong Yunhe , Zhao Jinmeng , Bian Shixiong , Ma Hui , Chen Jilan
Published: July 2022

Sexual maturation is fundamental to the reproduction and production performance, heterosis of which has been widely used in animal crossbreeding. However, the underlying mechanism have long remained elusive, despite its profound biological and agricultural significance. In the current study, the reciprocal crossing between White Leghorns and Beijing You chickens were performed to measure the sexual maturation heterosis, and the ovary lncRNAs and mRNAs of purebreds and crossbreeds were profiled to illustrate molecular mechanism of heterosis. Heterosis larger than 20% was found for pubic space and oviduct length, whereas age at first egg showed negative heterosis in both crossbreeds. We identified 1170 known lncRNAs and 1994 putative lncRNAs in chicken ovary using a stringent pipeline. Gene expression pattern showed that nonadditivity was predominant, and the proportion of nonadditive lncRNAs and genes was similar between two crossbreeds, ranging from 44.24% to 49.15%. A total of 200 lncRNAs and 682 genes were shared by two crossbreeds, respectively. GO and KEGG analysis showed that the common genes were significantly enriched in the cell cycle, animal organ development, gonad development, ECM-receptor interaction, calcium signaling pathway and GnRH signaling pathway. Weighted gene co-expression network analysis (WGCNA) identified that 7 out of 20 co-expressed lncRNA-mRNA modules significantly correlated with oviduct length and pubic space. Interestingly, genes harbored in seven modules were also enriched in the similar biological process and pathways, in which nonadditive lncRNAs, such as MSTRG.17017.1 and MSTRG.6475.20, were strongly associated with nonadditive genes, such as CACNA1C and TGFB1 to affect gonad development and GnRH signaling pathway, respectively. Moreover, the results of real-time quantitative PCR (RT-qPCR) correlated well with the transcriptome data. Integrated with positive heterosis of serum GnRH and melatonin content detected in crossbreeds, we speculated that nonadditive genes involved in the GnRH signaling pathway elevated the gonad development, leading to the sexual maturation heterosis. We characterized a systematic landscape of ovary lncRNAs and mRNAs related to sexual maturation heterosis in chicken. The quantitative exploration of hybrid transcriptome changes lays foundation for genetic improvement of sexual maturation traits and provides insights into endocrine control of sexual maturation.
Coexistence mechanisms of sympatric ungulates: Behavioral and physiological adaptations of blue sheep (Pseudois nayaur) and red deer (Cervus elaphus alxaicus) in Helan Mountains, China
Authors: Li Zongzhi , Wang Jifei , Khattak Romaan Hayat , Han Xingzhi , Liu Peng , Liu Zhensheng , Teng Liwei
Published: July 2022

Studying the coexistence mechanisms of sympatric wildlife helps to shed light on why the earth has so many different species. When ungulates share ranges, food and habitat requirements may partially or fully overlap. Therefore, the aim of this study was to determine how sympatric ungulates share limited resources. Carcasses of 27 adult blue sheep (Pseudois nayaur) and three adult red deer (Cervus elaphus alxaicus) were collected in the Helan Mountains, China. Nutritive indices of plant species foraged and morphometric measurements of the digestive system of the two sympatric ungulates were determined. In addition, 120 passive, infrared motion-triggered cameras recorded spatial overlap and temporal overlap between the two species. Camera trapping revealed relatively limited spatial overlap and significantly different activity rhythms between blue sheep and red deer. Differences were also observed in stomach weight, surface enlargement factor of the rumen, and intestine length between the two species. However, the combined relative weight of the stomach and intestine was not different between species. The low spatiotemporal overlap decreased opportunities for encounters between sympatric blue sheep and red deer, and significant differences in digestive systems allowed the two species to consume different plant species or different parts of the same species. Thus, the two sympatric ungulates coexist harmoniously in the Helan Mountains because of long-term evolutionary behavioral and physiological adaptations that eliminate negative effects on the survival of the other species.
Understory plant communities show resistance to drought, hurricanes, and experimental warming in a wet tropical forest
Authors: Alonso-Rodríguez Aura M. , Wood Tana E. , Torres-Díaz Jamarys , Cavaleri Molly A. , Reed Sasha C. , Bachelot Benedicte
Published: July 2022

Global climate change has led to rising temperatures and to more frequent and intense climatic events, such as storms and droughts. Changes in climate and disturbance regimes can have non-additive effects on plant communities and result in complicated legacies we have yet to understand. This is especially true for tropical forests, which play a significant role in regulating global climate. We used understory vegetation data from the Tropical Responses to Altered Climate Experiment (TRACE) in Puerto Rico to evaluate how plant communities responded to climate warming and disturbance. The TRACE understory vegetation was exposed to a severe drought (2015), 2 years of experimental warming (4°C above ambient in half of the plots, 2016–2017 and 2018–2019), and two major hurricanes (Irma and María, September 2017). Woody seedlings and saplings were censused yearly from 2015 to 2019, with an additional census in 2015 after the drought ended. We evaluated disturbance-driven changes in species richness, diversity, and composition across ontogeny. We then used Bayesian predictive trait modeling to assess how species responded to disturbance and how this might influence the functional structure of the plant community. Our results show decreased seedling richness after hurricane disturbance, as well as increased sapling richness and diversity after warming. We found a shift in species composition through time for both seedlings and saplings, yet the individual effects of each disturbance were not significant. At both ontogenetic stages, we observed about twice as many species responding to experimental warming as those responding to drought and hurricanes. Predicted changes in functional structure point to disturbance-driven functional shifts toward a mixture of fast-growing and drought-tolerant species. Our findings demonstrate that the tropical forest understory community is more resistant to climatic stressors than expected, especially at the sapling stage. However, early signs of changes in species composition suggest that, in a warming climate with frequent droughts and hurricanes, plant communities might shift over time toward fast-growing or drought-tolerant species.
Therapeutic potential of an anti-CCR9 mAb evidenced in xenografts of human CCR9+ tumors
Authors: Santamaria Silvia , Delgado Marisa , Botas Marta , Castellano Eva , Corraliza-Gorjon Isabel , Lafuente Paloma , Muñoz-Calleja Cecilia , Toribio Maria L. , Kremer Leonor , Garcia-Sanz Jose A.
Published: July 2022

Relapsed or refractory T acute lymphoblastic leukemia (T-ALL) still carries poor prognosis. Aiming to improve outcomes, the therapeutic potential of an anti-CCR9 monoclonal antibody (mAb 92R), targeting the human chemokine-receptor CCR9 is analyzed on orthotopic xenotransplants. 92R mAb treatment of mice carrying human CCR9+T-ALL cell lines or primary T cell leukemias inhibits tumor growth and increases survival. The therapeutic effects of 92R are specific and synergize with chemotherapeutic agents increasing survival. Furthermore, 92R decreases size of non-hematopoietic tumors with a forced CCR9 expression and of solid tumors generated by the pancreatic adenocarcinoma cell line AsPC-1. In addition, a humanized version of 92R mAb (Srb1) is also able to inhibit growth of CCR9+T-ALL tumor cellsin vivo, increasing survival 2.66-fold. Finally, 92R mAb prevents liver accumulation of infiltrates and reduces tumor cell numbers in already formed infiltrates. Thus, the humanized version of 92R mAb (Srb1), displays therapeutic potential for CCR9+tumor treatment and might represent one of the first therapeutic antibodies for precision medicine on T-ALL patients.
Promoting intestinal IgA production in mice by oral administration with anthocyanins
Authors: Liu Xuerun , Wang Luoyang , Zhuang Huiren , Yang Zhenghuan , Jiang Guoqiang , Liu Zheng
Published: July 2022

While recent years have witnessed ever-growing evidence on the prebiotic attributes of anthocyanins for treatment of microbiota-associated diseases, the complex interplay between anthocyanin uptake, the gut microbiota, and the intestinal mucosal immune system remains poorly understood. Here, we investigate the effects of bilberry anthocyanins on the gut microbiota composition and metabolism, and the intestinal mucosal immune system of mice. We observed an increased proportion of IgA-producing plasma cells in the mesenteric lymph nodes (MLNs) and an enhanced secretion of secretory immunoglobulin A (sIgA) and antimicrobial peptides in the small intestine. Small intestine transcriptome analysis further suggested that anthocyanins influenced IgA production. We found that oral administration of anthocyanins altered the gut microbiota through maintaining the anaerobic intestinal environment, promoting the secretion of sIgA and antimicrobial peptides, and downregulating cell motility and mobile genetic elements of commensal bacteria. These observations suggest that the oral administration of anthocyanins helps in maintaining intestinal homeostasis and thus it may find applications in immunotherapy and related fields.
Immunogenicity Risk Assessment of Spontaneously Occurring Therapeutic Monoclonal Antibody Aggregates
Authors: Swanson Michael D. , Rios Shantel , Mittal Sarita , Soder George , Jawa Vibha
Published: July 2022

Aggregates of therapeutic proteins have been associated with increased immunogenicity in pre-clinical models as well as in human patients. Recent studies to understand aggregates and their immunogenicity risks use artificial stress methods to induce high levels of aggregation. These methods may be less biologically relevant in terms of their quantity than those that occur spontaneously during processing and storage. Here we describe the immunogenicity risk due to spontaneously occurring therapeutic antibody aggregates using peripheral blood mononuclear cells (PBMC) and a cell line with a reporter gene for immune activation: THP-1 BLUE NFκB. The spontaneously occurring therapeutic protein aggregates were obtained from process intermediates and final formulated drug substance from stability retains. Spontaneously occurring aggregates elicited innate immune responses for several donors in a PBMC assay with cytokine and chemokine production as a readout for immune activation. Meanwhile, no significant adaptive phase responses to spontaneously occurring aggregate samples were detected. While the THP-1 BLUE NFκB cell line and PBMC assays both responded to high stress induced aggregates, only the PBMC from a limited subset of donors responded to processing-induced aggregates. In this case study, levels of antibody aggregation occurring at process relevant levels are lower than those induced by stirring and may pose lower risk in vivo. Our methodologies can further inform additional immunogenicity risk assessments using a pre-clinical in vitro risk assessment approach utilizing human derived immune cells.
Classification of colon adenocarcinoma based on immunological characterizations: Implications for prognosis and immunotherapy
Authors: Xu Midie , Chang Jinjia , Wang Wenfeng , Wang Xin , Wang Xu , Weng Weiwei , Tan Cong , Zhang Meng , Ni Shujuan , Wang Lei , Huang Zhaohui , Deng Zhenzhong , Li Wenhua , Huang Dan , Sheng Weiqi
Published: July 2022

Accurate immune molecular typing is pivotal for screening out patients with colon adenocarcinoma (COAD) who may benefit from immunotherapy and whose tumor microenvironment (TME) was needed for reprogramming to beneficial immune-mediated responses. However, little is known about the immune characteristic of COAD. Here, by calculating the enrichment score of immune characteristics in three online COAD datasets (TCGA-COAD, GSE39582, and GSE17538), we identified 17 prognostic-related immune characteristics that overlapped in at least two datasets. We determined that COADs could be stratified into three immune subtypes (IS1–IS3), based on consensus clustering of these 17 immune characteristics. Each of the three ISs was associated with distinct clinicopathological characteristics, genetic aberrations, tumor-infiltrating immune cell composition, immunophenotyping (immune “hot” and immune “cold”), and cytokine profiles, as well as different clinical outcomes and immunotherapy/therapeutic response. Patients with the IS1 tumor had high immune infiltration but immunosuppressive phenotype, IS3 tumor is an immune “hot” phenotype, whereas those with the IS2 tumor had an immune “cold” phenotype. We further verified the distinct immune phenotype of IS1 and IS3 by an in-house COAD cohort. We propose that the immune subtyping can be utilized to identify COAD patients who will be affected by the tumor immune microenvironment. Furthermore, the ISs may provide a guide for personalized cancer immunotherapy and for tumor prognosis.
Evaluation of the immune feature of ACPA-negative rheumatoid arthritis and the clinical value of matrix metalloproteinase-3
Authors: Liang Zhaojun , Wang Nan , Shang Lili , Wang Yanlin , Feng Min , Liu Guangying , Gao Chong , Luo Jing
Published: July 2022

Anti-citrullinated protein antibodies (ACPAs) are highly specific for the diagnosis of rheumatoid arthritis (RA). However, about one-third of RA patients are negative for ACPAs, which presents a challenge to the early diagnosis of RA. The purpose of this study was to analyze differences in lymphocyte subsets and CD4+ T cell subsets between ACPA+ and ACPA- RA patients, and to evaluate the value of matrix metalloproteinase-3 (MMP-3) as a diagnostic and monitoring marker in ACA- RA patients. A total of 145 ACPA+ RA patients, 145 ACPA- RA patients, and 38 healthy controls (HCs) were included in this study. Peripheral lymphocyte subsets were detected using flow cytometry, and serum MMP-3 was detected using chemiluminescence. Information about joint symptoms, other organ involvement, and related inflammatory markers was also collected. The results showed that, compared to ACPA- RA patients, ACPA+ cases had greater imbalances between peripheral CD4+ T cell subsets, mainly manifested as an increase in T-helper 1 (Th1) cells (p < 0.001) and decrease in regulatory T (Treg) cells (p = 0.029). This makes these patients more prone to inflammatory reactions and joint erosion. MMP-3 levels in ACPA+ and ACPA- RA patients were significantly higher than in HCs (p < 0.001), and MMP-3 could effectively distinguish between ACPA- RA patients and HCs (area under the curve [AUC] = 0.930, sensitivity 84.14%, specificity 92.11%). MMP-3 was also a serum marker for distinguishing between RA patients with low and high disease activities. Further analysis showed that MMP-3 was positively correlated with the levels of inflammatory markers and disease activity, and negatively correlated with the levels of lymphocyte subsets. In addition, with improvements in the disease, MMP-3 levels decreased, and further increased as the patients started to deteriorate. In summary, our research showed that there was a mild imbalance between peripheral CD4+ T cell subsets in ACPA- RA patients. MMP-3 may be used as a potential marker for early diagnosis of ACPA- RA. MMP-3 was an important index for RA disease evaluation, disease activity stratification, and prognosis.
A Study on the Radiosensitivity of Radiation-Induced Lung Injury at the Acute Phase Based on Single-Cell Transcriptomics
Authors: Ma Luyu , Ye Yumeng , Lu Hao , Xing Yuan , Zhao Zhen , Quan Cheng , Jia Zhaoqian , Lu Yiming , Li Yang , Zhou Gangqiao
Published: July 2022

Background and Aims

Radiation-induced lung injury (RILI) is the most common complication associated with chest tumors, such as lung and breast cancers, after radiotherapy; however, the pathogenic mechanisms are unclear. Single-cell RNA sequencing has laid the foundation for studying RILI at the cellular microenvironmental level. This study focused on changes during the acute pneumonitis stage of RILI at the cellular microenvironmental level and investigated the interactions between different cell types.

Methods

An acute RILI model in mice and a single-cell transcriptional library were established. Intercellular communication networks were constructed to study the heterogeneity and intercellular interactions among different cell types.

Results

A single-cell transcriptome map was established in a mouse model of acute lung injury. In total, 18,500 single-cell transcripts were generated, and 10 major cell types were identified. The heterogeneity and radiosensitivity of each cell type or subtype in the lung tissues during the acute stage were revealed. It was found that immune cells had higher radiosensitivity than stromal cells. Immune cells were highly heterogeneous in terms of radiosensitivity, while some immune cells had the characteristics of radiation resistance. Two groups of radiation-induced Cd8+Mki67+ T cells and Cd4+Cxcr6+ helper T cells were identified. The presence of these cells was verified using immunofluorescence. The ligand-receptor interactions were analyzed by constructing intercellular communication networks. These explained the origins of the cells and revealed that they had been recruited from endothelial cells to the inflammatory site.

Conclusions

This study revealed the heterogeneity of in vivo radiosensitivity of different cell types in the lung at the initial stage post irradiation
Antimicrobial Proteins and Peptides in Avian Eggshell: Structural Diversity and Potential Roles in Biomineralization
Authors: Moreau Thierry , Gautron Joël , Hincke Maxwell T. , Monget Philippe , Réhault-Godbert Sophie , Guyot Nicolas
Published: July 2022

The calcitic avian eggshell provides physical protection for the embryo during its development, but also regulates water and gaseous exchange, and is a calcium source for bone mineralization. The calcified eggshell has been extensively investigated in the chicken. It is characterized by an inventory of more than 900 matrix proteins. In addition to proteins involved in shell mineralization and regulation of its microstructure, the shell also contains numerous antimicrobial proteins and peptides (AMPPs) including lectin-like proteins, Bacterial Permeability Increasing/Lipopolysaccharide Binding Protein/PLUNC family proteins, defensins, antiproteases, and chelators, which contribute to the innate immune protection of the egg. In parallel, some of these proteins are thought to be crucial determinants of the eggshell texture and its resulting mechanical properties. During the progressive solubilization of the inner mineralized eggshell during embryonic development (to provide calcium to the embryo), some antimicrobials may be released simultaneously to reinforce egg defense and protect the egg from contamination by external pathogens, through a weakened eggshell. This review provides a comprehensive overview of the diversity of avian eggshell AMPPs, their three-dimensional structures and their mechanism of antimicrobial activity. The published chicken eggshell proteome databases are integrated for a comprehensive inventory of its AMPPs. Their biochemical features, potential dual function as antimicrobials and as regulators of eggshell biomineralization, and their phylogenetic evolution will be described and discussed with regard to their three-dimensional structural characteristics. Finally, the repertoire of chicken eggshell AMPPs are compared to orthologs identified in other avian and non-avian eggshells. This approach sheds light on the similarities and differences exhibited by AMPPs, depending on bird species, and leads to a better understanding of their sequential or dual role in biomineralization and innate immunity.
The role of interleukin-22 in lung health and its therapeutic potential for COVID-19
Authors: Fang Si , Ju Dianwen , Lin Yong , Chen Wei
Published: July 2022

Although numerous clinical trials have been implemented, an absolutely effective treatment against coronavirus disease 2019 (COVID-19) is still elusive. Interleukin-22 (IL-22) has attracted great interest over recent years, making it one of the best-studied cytokines of the interleukin-10 (IL-10) family. Unlike most interleukins, the major impact of IL-22 is exclusively on fibroblasts and epithelial cells due to the restricted expression of receptor. Numerous studies have suggested that IL-22 plays a crucial role in anti-viral infections through significantly ameliorating the immune cell-mediated inflammatory responses, and reducing tissue injury as well as further promoting epithelial repair and regeneration. Herein, we pay special attention to the role of IL-22 in the lungs. We summarize the latest progress in our understanding of IL-22 in lung health and disease and further discuss maneuvering this cytokine as potential immunotherapeutic strategy for the effective manage of COVID-19.
Natural killer cells: the next wave in cancer immunotherapy
Authors: Chen Xin , Jiang Lei , Liu Xuesong
Published: July 2022

Immunotherapies focusing on rejuvenating T cell activities, like PD-1/PD-L1 and CTLA-4 blockade, have unprecedentedly revolutionized the landscape of cancer treatment. Yet a previously underexplored component of the immune system - natural killer (NK) cell, is coming to the forefront of immunotherapeutic attempts. In this review, we discuss the contributions of NK cells in the success of current immunotherapies, provide an overview of the current preclinical and clinical strategies at harnessing NK cells for cancer treatment, and highlight that NK cell-mediated therapies emerge as a major target in the next wave of cancer immunotherapy.
Tumor-associated microglia and macrophages in glioblastoma: From basic insights to therapeutic opportunities
Authors: Wang Guoqing , Zhong Kunhong , Wang Zeng , Zhang Zongliang , Tang Xin , Tong Aiping , Zhou Liangxue
Published: July 2022

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Currently, the standard treatment of glioblastoma includes surgery, radiotherapy, and chemotherapy. Despite aggressive treatment, the median survival is only 15 months. GBM progression and therapeutic resistance are the results of the complex interactions between tumor cells and tumor microenvironment (TME). TME consists of several different cell types, such as stromal cells, endothelial cells and immune cells. Although GBM has the immunologically “cold” characteristic with very little lymphocyte infiltration, the TME of GBM can contain more than 30% of tumor-associated microglia and macrophages (TAMs). TAMs can release cytokines and growth factors to promote tumor proliferation, survival and metastasis progression as well as inhibit the function of immune cells. Thus, TAMs are logical therapeutic targets for GBM. In this review, we discussed the characteristics and functions of the TAMs and evaluated the state of the art of TAMs-targeting strategies in GBM. This review helps to understand how TAMs promote GBM progression and summarizes the present therapeutic interventions to target TAMs. It will possibly pave the way for new immune therapeutic avenues for GBM patients.
Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa
Authors: Petkov Stefan , Herrera Carolina , Else Laura , Mugaba Susan , Namubiru Patricia , Odoch Geoffrey , Opoka Daniel , Pillay Azure-Dee A. P. , Seiphetlo Thabiso B. , Serwanga Jennifer , Ssemata Andrew S. , Kaleebu Pontiano , Webb Emily L. , Khoo Saye , Lebina Limakatso , Gray Clive M. , Martinson Neil , Fox Julie , Chiodi Francesca
Published: July 2022

HIV-1 pre-exposure prophylaxis (PrEP) relies on inhibition of HIV-1 replication steps. To understand how PrEP modulates the immunological environment, we derived the plasma proteomic profile of men receiving emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during the CHAPS trial in South Africa and Uganda (NCT03986970). The CHAPS trial randomized 144 participants to one control and 8 PrEP arms, differing by drug type, number of PrEP doses and timing from final PrEP dose to sampling. Blood was collected pre- and post-PrEP. The inflammatory profile of plasma samples was analyzed using Olink (N=92 proteins) and Luminex (N=33) and associated with plasma drug concentrations using mass spectrometry. The proteins whose levels changed most significantly from pre- to post-PrEP were CCL4, CCL3 and TNF-α; CCL4 was the key discriminator between pre- and post-PrEP samples. CCL4 and CCL3 levels were significantly increased in post-PrEP samples compared to control specimens. CCL4 was significantly correlated with FTC drug levels in plasma. Production of inflammatory chemokines CCL4 and CCL3 in response to short-term PrEP indicates the mobilization of ligands which potentially block virus attachment to CCR5 HIV-1 co-receptor. The significant correlation between CCL4 and FTC levels suggests that CCL4 increase is modulated as an inflammatory response to PrEP.
Trophic Ecology of Deep-Sea Megafauna in the Ultra-Oligotrophic Southeastern Mediterranean Sea
Authors: Guy-Haim Tamar , Stern Nir , Sisma-Ventura Guy
Published: July 2022

The trophic ecology of fourteen species of demersal fishes and six species of demersal decapod crustaceans from the continental slope and rise of the Southeastern Mediterranean Sea (SEMS) was examined using stable isotope analysis. Mean δ13C values among fish species varied by ca. 4.0‰, from -20.85‰ (Macroramphosus scolopax) to -16.57‰ and -16.89‰ (Conger conger and Centrophorus granulosus), showing an enrichment in 13C as a function of depth (200 – 1400 m). Mean δ13C values of the crustaceans showed smaller variation, between -18.54‰ (Aristeus antennatus) and -16.38‰ (Polycheles typhlops). This suggests a shift from pelagic to regenerated benthic carbon sources with depth. Benthic carbon regeneration is further supported by the low benthic-pelagic POM-δ13C values, averaging -24.7 ± 1.2‰, and the mixing model results, presenting relatively low contribution of epipelagic POM to the deep-sea fauna. Mean δ15N values of fish and crustacean species ranged 7.91 ± 0.36‰ to 11.36 ± 0.39‰ and 5.96 ± 0.24‰ to 7.73 ± 0.46‰, respectively, resulting in trophic position estimates, occupying the third and the fourth trophic levels. Thus, despite the proximity to the more productive areas of the shelf, low number of trophic levels (TL~1.0) and narrow isotopic niche breadths (SEAC<1) were observed for demersal crustaceans (TL = 2.94 ± 0.18) and fishes (TL = 3.62 ± 0.31) in the study area – probably due to the ultra-oligotrophic state of the SEMS resulting in limited carbon sources. Our results, which provide the first trophic description of deep-sea megafauna in the SEMS, offer insight into the carbon sources and food web structure of deep-sea ecosystems in oligotrophic marginal seas, and can be further used in ecological modeling and support the sustainable management of marine resources in the deep Levantine Sea.
Si decline and diatom evolution: Insights from physiological experiments
Authors: Petrucciani Alessandra , Knoll Andrew H. , Norici Alessandra
Published: July 2022

In today’s oceans, diatoms are abundant and diverse primary producers distinguished by their silica shells. Although molecular clocks suggest that diatoms arose as much as 250 million years ago (Ma), the earliest known diatom fossils date from 190 Ma, leading to the suggestion that early diatoms were at best lightly silicified. By the Cretaceous Period, large circular (in cross section) diatoms with highly silicified frustules thrived in surface oceans, only later to be joined by species with elongated and thinner frustules, as well as lower SiO2 content. Decreased Si availability in surface oceans has been proposed as a principal driver of diatom evolution. Here, we investigate this through physiological experiments assessing the functional acclimation response of diatoms to reconstructed paleo-seawater. Four diatom species, differing in size and shape, were acclimated to reconstructed paleoenvironments mimicking Mesozoic/Cenozoic concentrations of nutrients in the presence of different Si regimes. When exposed to 500 µM Si, all populations, save for that of Conticribra weissflogii, became more highly silicified; the higher Si content per cell at 500 µM Si coincided with slower growth in small-sized cells. All species except C. weissflogii also showed lower photosynthetic efficiency as well as greater cell volume in comparison with diatoms acclimated to 205 or 25 µM Si. Average cell stoichiometry correlates with cell shape, but not size; pennates, in particular Phaeodactylum tricornutum, showed an acclimatory response to Si regimes, modulating Si use efficiency (the lower the external Si concentrations, the higher the C and N quotas per Si).

Experimental data suggest that in the densely silicified and bigger C. weissflogii grown at higher Si, diffusion of silicic acid across membranes made a larger contribution to Si uptake, saving energy which could be reallocated into growth. In contrast, for less highly silicified and smaller species, high energy costs of Si homeostasis needed to prevent the overaccumulation of intracellular Si limited growth. While our experimental species reacted individualistically to changing silica availability, with distinct levels of plasticity, selective pressure associated with the temporal decline in Si availability may well have favored elongated shapes. Modern, less silicified species are unable to exploit high Si concentrations.
Assessing trophic interactions among three tuna species in the Solomon Islands based on stomach contents and stable isotopes
Authors: Jiang Ri Jin , Yang Fan , Chen Feng , Yin Rui , Liu Ming Zhi , Zhu Wen Bin , Guo Ai , Liu Lian Wei
Published: July 2022

Trophic research is essential to the conservation and management of fishery resources. This study analyzed the feeding habits and nutritional interactions among three tuna species in the waters of the Solomon Islands (5°12′S–15°20′S, 157°31′E–172°19′E). A total of 103 bigeye tuna (Thunnus obesus), 296 yellowfin tuna (Thunnus albacores), and 264 albacore tuna (Thunnus alalunga) samples were collected from September to December 2019. Samples for stomach content and stable isotope analysis were randomly selected. The stomach content analysis results showed that the stomach contents of the three tuna species were rich in prey, and 48 prey species were identified, including fish, cephalopods, and crustaceans, with high between-phenotype component (BPC). Yellowfin tuna consumed the largest variety of food and bigeye tuna consumed the smallest. The feeding intensity of bigeye tuna were higher than that of yellowfin and albacore tuna. Yellowfin tuna had the highest empty stomach rate (35.69%) and lowest average stomach fullness index (0.064). The degree of stomach fullness in the three tuna species was mainly 1, and the difference in the stomach fullness index among them was significant (P<0.001). Food overlap (0.3–0.6) and Levins index (<0.6) among the three species were low, indicating a specialized feeding tendency. Bigeye tuna mainly feed on Ommastrephes bartrami and Myctophidae, yellowfin tuna mainly feed on Hyperiidea and Aluterus monoceros, and albacore tuna mainly feed on Gempylus serpens and Loligo chinensis. The stable isotope results showed that the δ13C and δ15N values of the three tuna species were significant (P<0.001). The standard ellipse area corrected for small sample sizes (SEAc) and total niche area (TA) of bigeye tuna, range of δ15N (NR) of yellowfin tuna, and range of δ13C (CR) of albacore tuna were the highest. The results of this study will help improve our understanding of the feeding ecology of these three tuna species and their important roles in the ecosystem and food web structure.
Recognition of behavior state of Penaeus vannamei based on passive acoustic technology
Authors: Wei Maochun , Chen Keyu , Lin Yating , Cheng En
Published: July 2022

Underwater signal processing based on passive acoustic technology has carried out a lot of research on the behavioral sound of underwater creatures and the protection of marine resources, which proves the feasibility of passive acoustic technology for long-term and non-destructive monitoring of underwater biological sound production. However, at present, most relevant research focuses on fish but little research on shrimp. At the same time, as the main economic breeding industry, Penaeus vannamei has a backward industrial structure, in which the level of intelligence needs to be improved. In this paper, the acoustic signals generated by different physiological behaviors of P. vannamei are collected based on passive acoustic technology. Their different behaviors are finally classified and identified through feature extraction and analysis. Meanwhile, the characteristic non-parametric ANOVA is carried out to explore the relationship between the acoustic signals and the behavior state of P. vannamei to achieve the purpose of real-time monitoring of the behavior state of P. vannamei. The experimental results show that linear prediction cepstrum coefficient (LPCC) and Mel-frequency cepstrum coefficient (MFCC) characteristic coefficients are effective in the classification and recognition of different behavioral acoustic signals with interspecific acoustic signals of P. vannamei. Meanwhile, the SVM classifier based on OvR classification strategy can model the acoustic signal characteristics of different underwater biological behaviors more efficiently and has classification accuracy as high as 93%.
Coinfection of COVID-19 and Dengue: A Case Report
Authors: Prapty Chowdhury Nusaiba Binte Sayed , Ahmed Nafisa , Araf Yusha , Yang Zhijun , Zhai Jingbo , Hosen Mohammad Jakir , Zheng Chunfu
Published: July 2022

While the COVID-19 pandemic takes the world by storm, dengue-endemic regions risk developing a co-epidemic in COVID-19/dengue coinfection. With both infections as causes of high morbidity rates, the potentially fatal outcomes of coinfection are even greater, and several cases are emerging, severe and moderate, showing how common it may become in certain regions. The case reported here shows a 38-year-old male patient with high-grade fever, with complaints of nausea, joint, and muscle aches, all characteristic symptoms of COVID-19 and dengue. Initially suspected of being infected with COVID-19 only, the RT-PCR test of the nasopharyngeal swab confirmed COVID-19 infection, while the positive reactivity to IgG and IgM in the Dengue Duo test revealed a dengue coinfection. Except for the persistent high fever, the Patient's symptoms were not severe, although the tests confirmed the infections to be “moderate to severe” and showed steady and rapid recovery. The tests showed some interesting results, which provided additional research opportunities. Overall, this case report illustrates the existence of coinfections in the Philippines, demonstrating the difficulty in distinguishing the two infections and the need for proper diagnosis, prevention, and management measures.
CT findings of Talaromyces marneffei infection among HIV patients with lymphadenopathy
Authors: Zhu Xiao-ling , Tang Guang-Xiao , Liu Xue-yan , Li Ran , Lv Sheng-xiu , Wang Guang-xian
Published: July 2022

Background

Talaromyces marneffei (T. marneffei) is an opportunistic fungal pathogen commonly found in human immunodeficiency virus (HIV) patients that often infects lymph nodes. Knowledge about the computed tomography (CT) characteristics of T. marneffei lymphadenopathy in HIV patients is limited. The aim of this study was to investigate the clinical and CT characteristics of T. marneffei lymphadenopathy to improve its diagnosis and promote recognition of this type of infection in radiology.

Methods

Between February 2019 and June 2021, we retrospectively reviewed the clinical features and CT characteristics of T. marneffei lymphadenopathy in 21 HIV patients.

Results

The clinical symptoms of T. marneffei infection are non-specific. Anemia (100%), fever (85.7%) and cough and sputum production (76.2%) were the most frequent symptoms. Multiple lymphadenopathies, mainly in the mediastinum (76.2%) and mesentery (82.4%), can be fused (14.3%) and necrotic (52.4%), with slight (41.7%) and moderate enhancement (58.3%) that is heterogeneous. In addition to involving the lymph nodes, the lesions involved the lungs (81.0%), liver and spleen (42.9%), and small intestine (14.3%).

Conclusions

T. marneffei is prone to affecting lymph nodes and extranodal organs in HIV patients. Although the clinical manifestations of T. marneffei infection are not specific, the possibility of T. marneffei infection should be considered if CT findings indicate multiple lesion sites.
Sulfonylureas or biguanides is associated with a lower risk of rheumatoid arthritis in patients with diabetes: A nationwide cohort study
Authors: Su Yu-Jih , Huang Jing-Yang , Chu Cong-Qiu , Wei James Cheng-Chung
Published: July 2022

Objective

Diabetes mellitus (DM) is associated with immune dysregulation, while sulfonylureas or biguanides have been linked to anti-inflammatory mechanisms. In this study, we aimed to examine the occurrence rate of rheumatoid arthritis (RA) among DM patients and its incidence rate between different treatments.

Methods

This cohort study used the Taiwan National Health Insurance Research Database between 1997 and 2013 to evaluate the primary outcomes of the preventive role of sulfonylureas or biguanides in the development of RA. We used the Chi-square test for categorical variables and Cox proportional hazard regression and log-rank test to explore the time for development of RA in DM patients. Logistic regression was adopted to estimate the odds ratio of RA in different dosages of medication exposure.

Results

Our cohort study included 94,141 DM cases. The risk of RA development of non-sulfonylureas/biguanides users among the DM group in each analysis was set as the reference, and the adjusted hazard ratio of RA in DM patients who were using sulfonylureas or biguanides was 0.73 (95% confidence interval 0.60–0.90). Within 1 year before the index date, compared with no-biguanides users, patients with more than 180 days of prescription of biguanides had a significantly lower RA risk. Similarly, the significantly lower risk of RA was still observed in DM patients who had more than 365 days of prescription of sulfonylurea within 2 or 3 years before the index date of first RA visit (all p < 0.05).

Conclusion

Our data suggest that sulfonylureas or biguanides are associated with a lower rate of RA development in patients with DM; the effect of biguanides appeared more rapid than that of sulfonylureas, but the sulfonylureas might have a longer effect on lowering RA development incidence.