bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Optimized Design of In-Vessel Retention–External Reactor Vessel Cooling Strategy and Negative Effect Assessment
Authors: Chen Peng , Wu Zijie , Zhan Dekui , Xia Shaoxiong , Zhao Xinhai
Published: February 2022

Due to large uncertainty, the effectiveness of in-vessel retention (IVR) with external reactor vessel cooling (ERVC) for high-power reactors cannot be fully demonstrated during the transient process. To optimize the current IVR-ERVC strategy, the concept of IVR-ERVC with in-vessel injection (IVI) is studied. Two feasible IVI designs are proposed: 1) using the passive IVR water tank to implement simultaneous water injection in-vessel and ex-vessel and 2) using the passive severe accident dedicated in-vessel injection tanks (SADITs) to implement water injection in-vessel. The research on the feasibility and effectiveness of IVI is performed, and the corresponding negative effects are analyzed. The calculation results by using MIDAC show that the two proposed IVI concepts can greatly delay the accident progression in the core and reduce the decay heat peak of the molten pool in the lower head, thereby improving the effectiveness of the current IVR-ERVC strategy. And the negative effects are within acceptable ranges.
Circular Economy in Wastewater Management—The Potential of Source-Separating Sanitation in Rural and Peri-Urban Areas of Northern Finland and Sweden
Authors: Lehtoranta Suvi , Laukka Vuokko , Vidal Brenda , Heiderscheidt Elisangela , Postila Heini , Nilivaara Ritva , Herrmann Inga
Published: February 2022

Current practices in wastewater management lead to inefficient recovery and reuse of nutrients and can result in environmental problems. Source separation systems have been shown to be an efficient way of recovering nutrients and energy from wastewaters, both in rural and urban context. Studies on nutrient recovery potential and life cycle impacts of source separation systems are mainly limited to small systems (for example a few households) while the impacts of upscaling source separation to a regional level have hardly been studied, especially in sparsely populated areas where the cost of the connection to a main treatment plant is higher. This study examines the regional nutrient balance of two source separation scenarios—black water separation and urine diversion—and compares them to the existing conventional wastewater system. The analysis comprises three sparsely populated regions of northern Finland and Sweden, including rural, peri-urban and urban areas. In addition, climate impacts are assessed based on existing life cycle assessment (LCA) studies. According to the results, by source separation it is possible to achieve a significant increase in the recovery rate of phosphorus (41–81%) and nitrogen (689–864%) compared to the conventional system. Depending on the region up to 65% of the mineral phosphorus and 60% of mineral nitrogen fertilisers could be theoretically replaced. Furthermore, the climate and eutrophication impacts would decrease with the implementation of such systems, but an increase in acidification may occur. However, even if the benefits of source separation systems are undisputed in terms of nutrient recovery, the implementation of such systems would to a large extent require an entire system change of the wastewater treatment sector and a wide paradigm change towards a circular economy.
Calcium-Mediated Regulation Promotes the Biofilm Formation of Two Novel Pyridine-Degrading Bacteria
Authors: Xiong Fuzhong , Wen Donghui , Li Qilin
Published: February 2022

In bioaugmented wastewater treatment systems, it is essential for recalcitrant pollutant-degrading bacteria to form biofilms. Inducing biofilm formation in these bacteria, however, is challenging as it involves multiple inter-related regulating pathways and environmental factors. Herein, we report the remarkable promoting effect of Ca2+ on biofilm formation of two novel pyridine-degrading bacteria with poor innate biofilm-forming capabilities, Pseudomonas sp. ZX01 and Arthrobacter sp. ZX07. The roles of Ca2+ in different biofilm development stages were investigated. Our data showed strong influences of Ca2+ on the initial attachment of the two strains onto positively charged glass surfaces by altering cell surface charge as well as the cation bridging effect. Contrary to many other biofilm promoting mechanisms, Ca2+ downregulated the extracellular polymeric substances (EPS) production per cell in both Pseudomonas sp. ZX01 and Arthrobacter sp. ZX07, while increasing biofilm biomass. This is attributed to the strong cationic bridging between Ca2+ and EPS which can elevate the efficiency of the extracellular products in binding bacterial cells. Furthermore, Ca2+ increased the protein-to-polysaccharide (PN/PS) ratio in biofilm EPS of both strains, which favored cell aggregation, and biofilm establishment by increasing the hydrophobicity of cell surfaces. More intriguingly, the intracellular c-di-GMP, which can drive the switch of bacterial lifestyle from planktonic state to biofilm state, was also elevated markedly by exogenous Ca2+. Taken together, these results would be of guidance for applying the two strains into bioaugmented biofilm reactors where Ca2+ supplement strategy can be employed to facilitate their biofilm formation on the surfaces of engineering carriers.
Pollen-Based Maps of Past Regional Vegetation Cover in Europe Over 12 Millennia—Evaluation and Potential
Authors: Githumbi Esther , Pirzamanbein Behnaz , Lindström Johan , Poska Anneli , Fyfe Ralph , Mazier Florence , Nielsen Anne Brigitte , Sugita Shinya , Trondman Anna-Kari , Woodbridge Jessie , Gaillard Marie-José
Published: February 2022

Realistic and accurate reconstructions of past vegetation cover are necessary to study past environmental changes. This is important since the effects of human land-use changes (e.g. agriculture, deforestation and afforestation/reforestation) on biodiversity and climate are still under debate. Over the last decade, development, validation, and application of pollen-vegetation relationship models have made it possible to estimate plant abundance from fossil pollen data at both local and regional scales. In particular, the REVEALS model has been applied to produce datasets of past regional plant cover at 1° spatial resolution at large subcontinental scales (North America, Europe, and China). However, such reconstructions are spatially discontinuous due to the discrete and irregular geographical distribution of sites (lakes and peat bogs) from which fossil pollen records have been produced. Therefore, spatial statistical models have been developed to create continuous maps of past plant cover using the REVEALS-based land cover estimates. In this paper, we present the first continuous time series of spatially complete maps of past plant cover across Europe during the Holocene (25 time windows covering the period from 11.7 k BP to present). We use a spatial-statistical model for compositional data to interpolate REVEALS-based estimates of three major land-cover types (LCTs), i.e., evergreen trees, summer-green trees and open land (grasses, herbs and low shrubs); producing spatially complete maps of the past coverage of these three LCTs. The spatial model uses four auxiliary data sets—latitude, longitude, elevation, and independent scenarios of past anthropogenic land-cover change based on per-capita land-use estimates (“standard” KK10 scenarios)—to improve model performance for areas with complex topography or few observations. We evaluate the resulting reconstructions for selected time windows using present day maps from the European Forest Institute, cross validate, and compare the results with earlier pollen-based spatially-continuous estimates for five selected time windows, i.e., 100 BP-present, 350–100 BP, 700–350 BP, 3.2–2.7 k BP, and 6.2–5.7 k BP. The evaluations suggest that the statistical model provides robust spatial reconstructions. From the maps we observe the broad change in the land-cover of Europe from dominance of naturally open land and persisting remnants of continental ice in the Early Holocene to a high fraction of forest cover in the Mid Holocene, and anthropogenic deforestation in the Late Holocene. The temporal and spatial continuity is relevant for land-use, land-cover, and climate research.
Comparative Analysis of Seed Transcriptome and Coexpression Analysis Reveal Candidate Genes for Enhancing Seed Size/Weight in Brassica juncea
Authors: Mathur Shikha , Paritosh Kumar , Tandon Rajesh , Pental Deepak , Pradhan Akshay K.
Published: February 2022

Seed size/weight is a multigenic trait that is governed by complex transcriptional regulatory pathways. An understanding of the genetic basis of seed size is of great interest in the improvement of seed yield and quality in oilseed crops. A global transcriptome analysis was performed at the initial stages of seed development in two lines of Brassica juncea, small-seeded EH-2 and large-seeded PJ. The anatomical analyses revealed significant differences in cell number and cell size in the outer layer of the seed coat between EH-2 and PJ. Pairwise comparisons at each developmental stage identified 5,974 differentially expressed genes (DEGs) between the two lines, of which 954 genes belong to different families of transcription factors. Two modules were found to be significantly correlated with an increased seed size using weighted gene coexpression network analysis. The DEG and coexpression datasets were integrated with the thousand seed weight (Tsw) quantitative trait loci (QTL) mapped earlier in the EPJ (EH-2 × PJ) doubled haploid (DH) population, which identified forty potential key components controlling seed size. The candidate genes included genes regulating the cell cycle, cell wall biogenesis/modification, solute/sugar transport, and hormone signaling. The results provide a valuable resource to widen the current understanding of regulatory mechanisms underlying seed size in B. juncea.
Novel Immune-Related Ferroptosis Signature in Esophageal Cancer: An Informatics Exploration of Biological Processes Related to the TMEM161B-AS1/hsa-miR-27a-3p/GCH1 Regulatory Network
Authors: Lu Min , Li Jiaqi , Fan Xin , Xie Fei , Fan Jie , Xiong Yuanping
Published: February 2022

Background: Considering the role of immunity and ferroptosis in the invasion, proliferation and treatment of cancer, it is of interest to construct a model of prognostic-related differential expressed immune-related ferroptosis genes (PR-DE-IRFeGs), and explore the ferroptosis-related biological processes in esophageal cancer (ESCA).

Methods: Four ESCA datasets were used to identify three PR-DE-IRFeGs for constructing the prognostic model. Validation of our model was based on analyses of internal and external data sets, and comparisons with past models. With the biological-based enrichment analysis as a guide, exploration for ESCA-related biological processes was undertaken with respect to the immune microenvironment, mutations, competing endogenous RNAs (ceRNA), and copy number variation (CNV). The model’s clinical applicability was measured by nomogram and correlation analysis between risk score and gene expression, and also immune-based and chemotherapeutic sensitivity.

Results: Three PR-DE-IRFeGs (DDIT3, SLC2A3, and GCH1), risk factors for prognosis of ESCA patients, were the basis for constructing the prognostic model. Validation of our model shows a meaningful capability for prognosis prediction. Furthermore, many biological functions and pathways related to immunity and ferroptosis were enriched in the high-risk group, and the role of the TMEM161B-AS1/hsa-miR-27a-3p/GCH1 network in ESCA is supported. Also, the KMT2D mutation is associated with our risk score and SLC2A3 expression. Overall, the prognostic model was associated with treatment sensitivity and levels of gene expression.

Conclusion: A novel, prognostic model was shown to have high predictive value. Biological processes related to immune functions, KMT2D mutation, CNV and the TMEM161B-AS1/hsa-miR-27a-3p/GCH1 network were involved in ESCA progression.
An Ensemble Learning Framework for Detecting Protein Complexes From PPI Networks
Authors: Wang Rongquan , Ma Huimin , Wang Caixia
Published: February 2022

Detecting protein complexes is one of the keys to understanding cellular organization and processes principles. With high-throughput experiments and computing science development, it has become possible to detect protein complexes by computational methods. However, most computational methods are based on either unsupervised learning or supervised learning. Unsupervised learning-based methods do not need training datasets, but they can only detect one or several topological protein complexes. Supervised learning-based methods can detect protein complexes with different topological structures. However, they are usually based on a type of training model, and the generalization of a single model is poor. Therefore, we propose an Ensemble Learning Framework for Detecting Protein Complexes (ELF-DPC) within protein-protein interaction (PPI) networks to address these challenges. The ELF-DPC first constructs the weighted PPI network by combining topological and biological information. Second, it mines protein complex cores using the protein complex core mining strategy we designed. Third, it obtains an ensemble learning model by integrating structural modularity and a trained voting regressor model. Finally, it extends the protein complex cores and forms protein complexes by a graph heuristic search strategy. The experimental results demonstrate that ELF-DPC performs better than the twelve state-of-the-art approaches. Moreover, functional enrichment analysis illustrated that ELF-DPC could detect biologically meaningful protein complexes. The code/dataset is available for free download from https://github.com/RongquanWang/ELF-DPC.
Tinker, Tailor, Tumour Suppressor: The Many Functions of PRP4K
Authors: Habib Elias B. , Mathavarajah Sabateeshan , Dellaire Graham
Published: February 2022

Pre-mRNA processing factor 4 kinase (PRP4K, also known as PRPF4B) is an essential kinase first identified in the fission yeast Schizosaccharomyces pombe that is evolutionarily conserved from amoebae to animals. During spliceosomal assembly, PRP4K interacts with and phosphorylates PRPF6 and PRPF31 to facilitate the formation of the spliceosome B complex. However, over the past decade additional evidence has emerged that PRP4K has many diverse cellular roles beyond splicing that contribute to tumour suppression and chemotherapeutic responses in mammals. For example, PRP4K appears to play roles in regulating transcription and the spindle assembly checkpoint (SAC), a key pathway in maintaining chromosomes stability and the response of cancer cells to taxane-based chemotherapy. In addition, PRP4K has been revealed to be a haploinsufficient tumour suppressor that promotes aggressive cancer phenotypes when partially depleted. PRP4K is regulated by both the HER2 and estrogen receptor, and its partial loss increases resistance to the taxanes in multiple malignancies including cervical, breast and ovarian cancer. Moreover, ovarian and triple negative breast cancer patients harboring tumours with low PRP4K expression exhibit worse overall survival. The depletion of PRP4K also enhances both Yap and epidermal growth factor receptor (EGFR) signaling, the latter promoting anoikis resistance in breast and ovarian cancer. Finally, PRP4K is negatively regulated during epithelial-to-mesenchymal transition (EMT), a process that promotes increased cell motility, drug resistance and cancer metastasis. Thus, as we discuss in this review, PRP4K likely plays evolutionarily conserved roles not only in splicing but in a number of cellular pathways that together contribute to tumour suppression.
CerealESTDb: A Comprehensive Resource for Abiotic Stress-Responsive Annotated ESTs With Predicted Genes, Gene Ontology, and Metabolic Pathways in Major Cereal Crops
Authors: Kumar Sanjeev , Bhati Jyotika , Saha Arijit , Lal Shashi Bhushan , Pandey Pankaj Kumar , Mishra Dwijesh Chandra , Farooqi Mohammad Samir , Kumar Anuj , Chaturvedi Krishna Kumar , Rai Anil
Published: February 2022

Cereals are the most important food crops and are considered key contributors to global food security. Loss due to abiotic stresses in cereal crops is limiting potential productivity in a significant manner. The primary reasons for abiotic stresses are abrupt temperature, variable rainfall, and declining nutrient status of the soil. Varietal development is the key to sustaining productivity under influence of multiple abiotic stresses and must be studied in context with genomics and molecular breeding. Recently, advances in a plethora of Next Generation Sequencing (NGS) based methods have accelerated the enormous genomic data generation associated with stress-induced transcripts such as microarray, RNAseq, Expressed Sequenced Tag (ESTs), etc. Many databases related to microarray and RNA-seq based transcripts have been developed and profusely utilized. However, an abundant amount of transcripts related to abiotic stresses in various cereal crops arising from EST technology are available but still remain underutilized in absence of a consolidated database. In this study, an attempt has been made with a primary goal to integrate, analyse, and characterise the available resources of ESTs responsive to abiotic stresses in major cereals. The developed CerealESTdb presents a customisable search in two different ways in the form of searchable content for easy access and potential use. This database comprises ESTs from four major cereal crops, namely rice (Oryza sativa L.), wheat (Triticum aestivum L.), sorghum (Sorghum bicolour L.), and maize (Zea mays L.), under a set of abiotic stresses. The current statistics of this cohesive database consists of 55,826 assembled EST sequences, 51,791 predicted genes models, and their 254,609 gene ontology terms including extensive information on 1,746 associated metabolic pathways. We anticipate that developed CerealESTdb will be helpful in deciphering the knowledge of complex biological phenomena under abiotic stresses to accelerate the molecular breeding programs towards the development of crop cultivars resilient to abiotic stresses. The CerealESTdb is publically available with the URL http://cabgrid.res.in/CerealESTDb.
Molecular and Physiological Aspects of SARS-CoV-2 Infection in Women and Pregnancy
Authors: Liu Anna , Raja xavier Janet , Singh Yogesh , Brucker Sara Y. , Salker Madhuri S.
Published: February 2022

Whilst scientific knowledge about SARS-CoV-2 and COVID-19 is rapidly increasing, much of the effects on pregnant women is still unknown. To accommodate pregnancy, the human endometrium must undergo a physiological transformation called decidualization. These changes encompass the remodeling of endometrial immune cells leading to immunotolerance of the semi-allogenic conceptus as well as defense against pathogens. The angiotensin converting enzyme 2 (ACE2) plays an important regulatory role in the renin-angiotensin-system (RAS) and has been shown to be protective against comorbidities known to worsen COVID-19 outcomes. Furthermore, ACE2 is also crucial for decidualization and thus for early gestation. An astounding gender difference has been found in COVID-19 with male patients presenting with more severe cases and higher mortality rates. This could be attributed to differences in sex chromosomes, hormone levels and behavior patterns. Despite profound changes in the female body during pregnancy, expectant mothers do not face worse outcomes compared with non-pregnant women. Whereas mother-to-child transmission through respiratory droplets during labor or in the postnatal period is known, another question of in utero transmission remains unanswered. Evidence of placental SARS-CoV-2 infection and expression of viral entry receptors at the maternal-fetal interface suggests the possibility of in utero transmission. SARS-CoV-2 can cause further harm through placental damage, maternal systemic inflammation, and hindered access to health care during the pandemic. More research on the effects of COVID-19 during early pregnancy as well as vaccination and treatment options for gravid patients is urgently needed.
Working Memory During Late Pregnancy: Associations With Antepartum and Postpartum Depression Symptoms
Authors: Liakea Iliana , K. C. Ashish , Bränn Emma , Fransson Emma , Sundström Poromaa Inger , Papadopoulos Fotios C. , Skalkidou Alkistis
Published: February 2022

Background

Few studies, with conflicting results, report on the association between memory performance and depressive symptoms during the perinatal period. In this study, we aimed to evaluate whether memory performance during late pregnancy is associated with antepartum (APD) and postpartum depression (PPD) symptoms.

Method

We conducted a prospective follow-up of 283 pregnant women, nested within a large cohort of women enrolled in the BASIC study in Uppsala University hospital between 2009 and 2019. The Wechsler Digit Span Task (forward-DSF, backward-DSB and total score-DST) was performed to evaluate short-term memory/attention (DSF) and working memory (DSB) around the 38th gestational week; the Edinburgh Postnatal Depression Scale (EPDS), evaluating depressive symptoms, was filled out at 17, 32, 38 gestational weeks, as well as at 6 weeks postpartum. Unadjusted and multivariate logistic regression was used to assess the association between performance on the Digit Span Task and outcome, namely depressive symptoms (using a cut-off of 12 points on the EPDS) at 38 gestational weeks, as well as at 6 weeks postpartum.

Results

APD symptoms were not significantly associated with DSF (p = 0.769) or DSB (p = 0.360). APD symptoms were significantly associated with PPD symptoms (p < 0.001). Unadjusted regression modeling showed that DSF in pregnancy was a significant predictor of PPD symptoms (OR 1.15; 95% CI, 1.00, 1.33, p = 0.049), and remained a significant predictor when adjusted for confounders (education and feeling rested at assessment; OR 1.21, 95% CI 1.03, 1.42, p = 0.022). DSF was a predictor of PPD symptoms only for women without a pre-pregnancy history of depression (OR 1.32; 95% CI 1.04, 1.67, p = 0.024) and also those without APD (OR 1.20, 95% CI 1.01, 1.43, p = 0.040).

Conclusion

There was no significant association between working and short-term memory performance and APD symptoms. Among all women, but especially non-depressed earlier in life and/or at antepartum, those scoring high on the forward memory test, i.e., short-term memory, had a higher risk for PPD. Future studies are required to further explore the pathophysiology behind and the predictive value of these associations.
DNA Vaccines Expressing the Envelope and Membrane Proteins Provide Partial Protection Against SARS-CoV-2 in Mice
Authors: Chen Jinni , Deng Yao , Huang Baoying , Han Di , Wang Wen , Huang Mengjing , Zhai Chengcheng , Zhao Zhimin , Yang Ren , Zhao Ying , Wang Wenling , Zhai Desheng , Tan Wenjie
Published: February 2022

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency of international concern, and an effective vaccine is urgently needed to control the pandemic. Envelope (E) and membrane (M) proteins are highly conserved structural proteins among SARS-CoV-2 and SARS-CoV and have been proposed as potential targets for the development of cross-protective vaccines. Here, synthetic DNA vaccines encoding SARS-CoV-2 E/M proteins (called p-SARS-CoV-2-E/M) were developed, and mice were immunised with three doses via intramuscular injection and electroporation. Significant cellular immune responses were elicited, whereas no robust humoral immunity was detected. In addition, novel H-2d-restricted T-cell epitopes were identified. Notably, although no drop in lung tissue virus titre was detected in DNA-vaccinated mice post-challenge with SARS-CoV-2, immunisation with either p-SARS-CoV-2-E or p-SARS-CoV-2-M provided minor protection and co-immunisation with p-SARS-CoV-2-E+M increased protection. Therefore, E/M proteins should be considered as vaccine candidates as they may be valuable in the optimisation of vaccination strategies against COVID-19.
SARS-CoV-2 Induces Cytokine Responses in Human Basophils
Authors: Bonam Srinivasa Reddy , Chauvin Camille , Levillayer Laurine , Mathew Mano Joseph , Sakuntabhai Anavaj , Bayry Jagadeesh
Published: February 2022

Basophils play a key role in the orientation of immune responses. Though the interaction of SARS-CoV-2 with various immune cells has been relatively well studied, the response of basophils to this pandemic virus is not characterized yet. In this study, we report that SARS-CoV-2 induces cytokine responses and in particular IL-13, in both resting and IL-3 primed basophils. The response was prominent under IL-3 primed condition. However, either SARS-CoV-2 or SARS-CoV-2-infected epithelial cells did not alter the expression of surface markers associated with the activation of basophils, such as CD69, CD13 and/or degranulation marker CD107a. We also validate that human basophils are not permissive to SARS-CoV-2 replication. Though increased expression of immune checkpoint molecule PD-L1 has been reported on the basophils from COVID-19 patients, we observed that SARS-CoV-2 does not induce PD-L1 on the basophils. Our data suggest that basophil cytokine responses to SARS-CoV-2 might help in reducing the inflammation and also to promote antibody responses to the virus.
Energy Metabolism-Related Gene Prognostic Index Predicts Biochemical Recurrence for Patients With Prostate Cancer Undergoing Radical Prostatectomy
Authors: Feng Dechao , Shi Xu , Zhang Facai , Xiong Qiao , Wei Qiang , Yang Lu
Published: February 2022

Background

We aimed to construct and validate an energy metabolism-related gene prognostic index (EMRGPI) to predict biochemical recurrence (BCR) in patients undergoing radical prostatectomy.

Methods

We used Lasso and COX regression analysis to orchestrate the EMRGPI in the TCGA database, and the prognostic value of EMRGPI was further validated externally using the GSE46602. All analyses were conducted with R version 3.6.3 and its suitable packages.

Results

SDC1 and ADH1B were finally used to construct the risk formula. We classified the 430 tumor patients in the TCGA database into two groups, and patients in the high-risk group had a higher risk of BCR than those in the low-risk group (HR: 1.98, 95%CI: 1.18-3.32, p=0.01). Moreover, in the GSE46602, we confirmed that the BCR risk in the high-risk group was 3.86 times higher than that in the low-risk group (95%CI: 1.61-9.24, p=0.001). We found that patients in the high-risk group had significantly higher proportions of residual tumor, older age, and T stage. SDC1 and ADH1B were significantly expressed low in the normal tissues when compared to the tumor tissues, which were opposite at the protein level. The spearman analysis showed that EMRGPI was significantly associated with B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score, and estimate score. In addition, the EMRGPI was positively associated with the 54 immune checkpoints, among which CD80, ADORA2A, CD160, and TNFRSF25 were significantly related to the BCR-free survival of PCa patients undergoing RP.

Conclusions

The EMRGPI established in this study might serve as an independent risk factor for PCa patients undergoing radical prostatectomy.
Memory B Cells Induced by Sputnik V Vaccination Produce SARS-CoV-2 Neutralizing Antibodies Upon Ex Vivo Restimulation
Authors: Byazrova Maria G. , Kulemzin Sergey V. , Astakhova Ekaterina A. , Belovezhets Tatyana N. , Efimov Grigory A. , Chikaev Anton N. , Kolotygin Ilya O. , Gorchakov Andrey A. , Taranin Alexander V. , Filatov Alexander V.
Published: February 2022

The development of effective vaccines against SARS-CoV-2 remains a global health priority. Despite extensive use, the effects of Sputnik V on B cell immunity need to be explored in detail. We performed comprehensive profiling of humoral and B cell responses in a cohort of vaccinated subjects (n = 22), and demonstrate that Sputnik vaccination results in robust B cell immunity.

We show that B memory cell (MBC) and antibody responses to Sputnik V were heavily dependent on whether the vaccinee had a history of SARS-CoV-2 infection or not. 85 days after the first dose of the vaccine, ex vivo stimulated MBCs from the vast majority of Sputnik V vaccinees produced antibodies that robustly neutralized the Wuhan Spike-pseudotyped lentivirus. MBC-derived antibodies from all previously infected and some of the naïve vaccine recipients could also cross-neutralize Beta (B.1.351) variant of SARS-CoV-2.

Virus-neutralizing activity of MBC-derived antibodies correlated well with that of the serum antibodies, suggesting the interplay between the MBC and long-lived plasma cell responses. Thus, our in-depth analysis of MBC responses in Sputnik V vaccinees complements traditional serological approaches and may provide important outlook into future B cell responses upon re-encounter with the emerging variants of SARS-CoV-2.
Examination of IgG Fc Receptor CD16A and CD64 Expression by Canine Leukocytes and Their ADCC Activity in Engineered NK Cells
Authors: Hullsiek Robert , Li Yunfang , Snyder Kristin M. , Wang Sam , Di Da , Borgatti Antonella , Lee Chae , Moore Peter F. , Zhu Cong , Fattori Chiara , Modiano Jaime F. , Wu Jianming , Walcheck Bruce
Published: February 2022

Human natural killer (NK) cells can target tumor cells in an antigen-specific manner by the recognition of cell bound antibodies. This process induces antibody-dependent cell-mediated cytotoxicity (ADCC) and is exclusively mediated by the low affinity IgG Fc receptor CD16A (FcγRIIIA). Exploiting ADCC by NK cells is a major area of emphasis for advancing cancer immunotherapies. CD64 (FcγRI) is the only high affinity IgG FcR and it binds to the same IgG isotypes as CD16A, but it is not expressed by human NK cells. We have generated engineered human NK cells expressing recombinant CD64 with the goal of increasing their ADCC potency. Preclinical testing of this approach is essential for establishing efficacy and safety of the engineered NK cells. The dog provides particular advantages as a model, which includes spontaneous development of cancer in the setting of an intact and outbred immune system. To advance this immunotherapy model, we cloned canine CD16A and CD64 and generated specific mAbs. We report here for the first time the expression patterns of these FcγRs on dog peripheral blood leukocytes. CD64 was expressed by neutrophils and monocytes, but not lymphocytes, while canine CD16A was expressed at high levels by a subset of monocytes and lymphocytes. These expression patterns are similar to that of human leukocytes. Based on phenotypic characteristics, the CD16A+lymphocytes consisted of T cells (CD3+CD8+CD5dimα/β TCR+) and NK cells (CD3−CD5−CD94+), but not B cells. Interestingly, the majority of canine CD16A+lymphocytes were from the T cell population. Like human CD16A, canine CD16A was downregulated by a disintegrin and metalloproteinase 17 (ADAM17) upon leukocyte activation, revealing a conserved means of regulation. We also directly demonstrate that both canine CD16A and CD64 can induce ADCC when expressed in the NK cell line NK-92. These findings pave the way to engineering canine NK cells or T cells with high affinity recombinant canine CD64 to maximize ADCC and to test their safety and efficacy to benefit both humans and dogs.
Role of Histone Post-Translational Modifications in Inflammatory Diseases
Authors: Lin Yingying , Qiu Ting , Wei Guifeng , Que Yueyue , Wang Wenxin , Kong Yichao , Xie Tian , Chen Xiabin
Published: February 2022

Inflammation is a defensive reaction for external stimuli to the human body and generally accompanied by immune responses, which is associated with multiple diseases such as atherosclerosis, type 2 diabetes, Alzheimer’s disease, psoriasis, asthma, chronic lung diseases, inflammatory bowel disease, and multiple virus-associated diseases. Epigenetic mechanisms have been demonstrated to play a key role in the regulation of inflammation. Common epigenetic regulations are DNA methylation, histone modifications, and non-coding RNA expression; among these, histone modifications embrace various post-modifications including acetylation, methylation, phosphorylation, ubiquitination, and ADP ribosylation. This review focuses on the significant role of histone modifications in the progression of inflammatory diseases, providing the potential target for clinical therapy of inflammation-associated diseases.
Anticyclonic Eddy Driving Significant Changes in Prokaryotic and Eukaryotic Communities in the South China Sea
Authors: Sun Fulin , Xia Xiaomin , Simon Meinhard , Wang Youshao , Zhao Hui , Sun Cuici , Cheng Hao , Wang Yutu , Hu Shuibo , Fei Jiao , Wu Meilin
Published: February 2022

Mesoscale eddies play an important role in ocean energy and material transport. However, the effect of eddies on bacterial and eukaryotic community and their ecological effects remains unclear, regarding anticyclonic eddies (ACE). In this study, bacterial and eukaryotic community composition was examined across an ACE in the South China Sea, using high-throughput sequencing of the 16S rRNA and 18S rRNA gene. Environmental variables reflected the hydrographic characteristics of the ACE, which enhanced bacterial diversity and eukaryotic diversity in most water layers, relative to adjacent regions. Principal component analysis (PCoA) showed that bacterial and eukaryotic communities had certain different compositions between inside and outside the eddy above 75 m water. An obvious effect of the ACE was the increase in abundance and depth distribution of small photosynthetic and heterotrophic bacteria, such as SAR11, Prochlorococcus, Rhodospirillales and Oceanospirillales. While ACE decreased the relative abundance of nutrient-rich phytoplankton (Bacillariophyta and Mamiellophyceae), resulted in more growth space for other eukaryotes that prefer oligotrophic environment (especially Fungi, Dictyochophyceae, and Synurophyceae). Canonical correlation analysis (CCA) showed temperature, salinity, nitrate, phosphate and nitrite had significantly affected on microbial community. The special environment of ACE (especially temperature) shaped the composition of its specific microbe. This study shed important light on the effect of ACEs on environmental conditions to impact marine ecosystem structure.
SSR Marker-Based Genetic Resource Assessment of the Rainbow Clam Moerella iridescens Along the Coasts of China: Implications for Strategy of Conservation Management
Authors: Li Xiaoying , Gao Shan , Zhao Manman , Dong Zhiguo
Published: February 2022

This study aims to determine the genetic structure of rainbow clam Moerella iridescens in different sea areas of China. Seventeen pairs of microsatellite primers (SSR) were used to amplify the SSRs of rainbow clam in Lianyungang of Haizhou Bay, Chongming of Shanghai, Ningde of Fujian, Daishan of Zhoushan, and Cixi and Wenzhou of Zhejiang. A total of 1,146 alleles were detected in 310 individuals from the 17 SSR loci. The average observed heterozygosity of six populations was 0.4381−0.6139, the average expected heterozygosity was 0.5897−0.7325, and the average Shannon diversity index was 1.2655−1.7998. The clams exhibited rich genetic diversity, and the FST of the genetic differentiation index of the six populations was 0.0470, indicating low genetic differentiation among the populations. The results indicated that rainbow clams along the coasts of China exhibited high diversity and low population differentiation.
Case Report: Early Distant Metastatic Inflammatory Myofibroblastic Tumor Harboring EML4-ALK Fusion Gene: Study of Two Typical Cases and Review of Literature
Authors: Han Qianqian , He Xin , Cui Lijuan , Qiu Yan , Li Yuli , Chen Huijiao , Zhang Hongying
Published: February 2022

Inflammatory myofibroblastic tumor (IMT) is a distinctive neoplasm that frequently arises in the lung and accounts for ~1% of lung tumors. Distant metastatic IMT is extremely rare and has been poorly investigated. This analysis was specifically performed to explore the clinicopathological and genetic features of early distant metastatic IMT. Two typical patients with distant metastatic IMTs were selected, which accounted for 1.13% of all diagnosed IMTs in the last 5 years. One patient was a 55 year-old male, and the other patient was a 56 year-old female. Both primary tumors arose from the lung, and the initial clinical symptoms of the two patients involved coughing. Both of the imaging examinations showed low-density nodular shadows in the lungs with enhancement around the mass. Microscopically, dense arranged tumor cells, prominent cellular atypia, and high mitotic activity with atypical form were more prominent in the metastatic lesions than in the primary lesions. All of the primary and metastatic tumors in both cases showed positive anaplastic lymphoma kinase (ALK) immunostaining and ALK rearrangement via fluorescence in situ hybridization. The EML4 (exon 6)-ALK (exon 20) fusion variant (v3a/b) was identified by using next-generation sequencing (NGS) and was verified by using reverse transcription polymerase chain reaction (RT-PCR). Furthermore, intronic variants of NOTCH1 and synonymous variants of ARAF were also detected via NGS in one IMT for the first time and were verified in all of the primary and metastatic lesions via PCR. Distant metastasis occurred during a short period of time (1 and 2 months) after the first surgery. One patient presented with multiple metastases to the subcutaneous tissue and bone that responded to ALK inhibitor alectinib therapy, and the tumor was observed to regress 10 months after the initial ALK inhibitor therapy. In contrast, the other patient presented with subcutaneous neck metastasis without ALK inhibitor treatment and succumbed to the disease within 3 months after the surgery. This study demonstrated the possible role of EML4-ALKv3a/b in the malignant progression of IMT and proposed certain therapeutic effects of ALK inhibitors on multiple metastatic IMTs.
Solving the Evidence Interpretability Crisis in Health Technology Assessment: A Role for Mechanistic Models?
Authors: Courcelles Eulalie , Boissel Jean-Pierre , Massol Jacques , Klingmann Ingrid , Kahoul Riad , Hommel Marc , Pham Emmanuel , Kulesza Alexander
Published: February 2022

Health technology assessment (HTA) aims to be a systematic, transparent, unbiased synthesis of clinical efficacy, safety, and value of medical products (MPs) to help policymakers, payers, clinicians, and industry to make informed decisions. The evidence available for HTA has gaps—impeding timely prediction of the individual long-term effect in real clinical practice. Also, appraisal of an MP needs cross-stakeholder communication and engagement. Both aspects may benefit from extended use of modeling and simulation. Modeling is used in HTA for data-synthesis and health-economic projections. In parallel, regulatory consideration of model informed drug development (MIDD) has brought attention to mechanistic modeling techniques that could in fact be relevant for HTA. The ability to extrapolate and generate personalized predictions renders the mechanistic MIDD approaches suitable to support translation between clinical trial data into real-world evidence. In this perspective, we therefore discuss concrete examples of how mechanistic models could address HTA-related questions. We shed light on different stakeholder's contributions and needs in the appraisal phase and suggest how mechanistic modeling strategies and reporting can contribute to this effort. There are still barriers dissecting the HTA space and the clinical development space with regard to modeling: lack of an adapted model validation framework for decision-making process, inconsistent and unclear support by stakeholders, limited generalizable use cases, and absence of appropriate incentives. To address this challenge, we suggest to intensify the collaboration between competent authorities, drug developers and modelers with the aim to implement mechanistic models central in the evidence generation, synthesis, and appraisal of HTA so that the totality of mechanistic and clinical evidence can be leveraged by all relevant stakeholders.
Where National Medicines Policies Have Taken Us With Patient Involvement and Health Technology Assessment in Africa
Authors: Sehmi Kawaldip , Wale Janet L.
Published: February 2022

The Covid-19 pandemic has highlighted global knowledge about, but lack of equitable access to, life-changing medicines, and other innovative medical products by populations in African low and middle income countries. The World Health Organization (WHO) and other international non-profit foundations and organizations are constantly striving to address inequity. In the 1970s, WHO initiated a regularly updated essential medicines list, together with the concept of national medicines policies (NMPs) to ensure access and availability, affordability, rational, and effective use of medicines which are considered essential in addressing predominant population health issues and disease burden. We studied the NMPs of Ghana, South Africa, Uganda and Zimbabwe to highlight some of the important issues that these countries experience in the safe and effective use of medical products. Thailand is an example of how health technology assessment (HTA) can provide a country with an internationally supported, clearly defined and transparent process to broaden access to medicines and services. These medical services can add considerable value in accordance with local values and priorities. Involvement of civil society adds democratic legitimacy to such processes. Community health workers and patient advocacy groups are important in raising awareness and knowledge of safety issues and the effective use of quality medicines. They can apply pressure for increased funding to improve access to healthcare. Medicines and services that contribute to supported self-care are of benefit in any setting. Joint efforts across African countries such as with the African Medicines Agency are important in addressing some of the major health issues.
Interactions Between Phenolic Acids and Microorganisms in Rhizospheric Soil From Continuous Cropping of Panax notoginseng
Authors: Bao Limei , Liu Yuyan , Ding Yafang , Shang Junjie , Wei Yunlin , Tan Yong , Zi Futing
Published: February 2022

Large-scale intensive cultivation has made continuous cropping soil sickness more serious for Panax notoginseng in Yunnan. Autotoxic substances can promote the occurrence of continuous cropping soil sickness. Phenolic acids exert a strong autotoxic effect on P. notoginseng. Based on UPLC-MS/MS, the levels of six phenolic acids with the strongest autotoxicity of P. notoginseng rhizospheric soil were tested. Based on Illumina MiSeq high-throughput sequencing technology, the variation in the microbial diversity in the rhizospheric soil was used as an index to explore the interactions between phenolic acids and the soil microorganisms of the P. notoginseng rhizosphere. (1) Continuous P. notoginseng cropping significantly changed the microbial community structure. Continuous cropping increased bacterial Chao1 index and Shannon index and decreased fungal Shannon index. After P. notoginseng disease, bacterial Shannon index reduced and fungal Chao1 index decreased. (2) Phenolic acid significantly changed the bacterial community structure. VA significantly reduced the bacterial Shannon index. Exogenous p-HA, FA, SA, and VA significantly increased the fungal Chao1 index and p-HA showed the most significant effect. Para-HA affected bacterial specificity, and VA affected fungal specificity. (3) VA was positively correlated with most fungi and bacteria. Para-HA was positively correlated with Lelliottia and Flavobacterium. Para-HA was also positively correlated with plant pathogens (Fusarium and Ilyonectria). Para-HA and VA were able to promote the growth of primary pathogenic bacteria. Thus, p-HA and VA are the main phenolic acid-autotoxin substances in P. notoginseng under continuous cropping. (4) A correlation analysis of soil environmental factors associated with fungal and bacterial communities showed that AK, TN, OM, and HN were most strongly correlated with soil microorganisms. (5) The microorganisms in the rhizosphere of 3-year-old soil planted with P. notoginseng exhibited obvious effects on the degradation of the four phenolic acids. The effect of soil microorganisms on phenolic acids was first-order kinetic degradation with a high degradation rate and a half-life of less than 4.5 h. The results showed that phenolic acids could promote the growth of pathogenic bacteria. And the interaction between rhizospheric soil microorganisms and phenolic acids was the main cause of the disturbance of P. notoginseng rhizosphere microflora.
Salicylic Acid-Mediated Disturbance Increases Bacterial Diversity in the Phyllosphere but Is Overcome by a Dominant Core Community
Authors: Vincent Stacey A. , Ebertz Andreas , Spanu Pietro D. , Devlin Paul F.
Published: February 2022

Plant microbiomes and immune responses have coevolved through history, and this applies just as much to the phyllosphere microbiome and defense phytohormone signaling. When in homeostasis, the phyllosphere microbiome confers benefits to its host. However, the phyllosphere is also dynamic and subject to stochastic events that can modulate community assembly. Investigations into the impact of defense phytohormone signaling on the microbiome have so far been limited to culture-dependent studies; or focused on the rhizosphere. In this study, the impact of the foliar phytohormone salicylic acid (SA) on the structure and composition of the phyllosphere microbiome was investigated. 16S rRNA amplicons were sequenced from aerial tissues of two Arabidopsis mutants that exhibit elevated SA signaling through different mechanisms. SA signaling was shown to increase community diversity and to result in the colonization of rare, satellite taxa in the phyllosphere. However, a stable core community remained in high abundance. Therefore, we propose that SA signaling acts as a source of intermediate disturbance in the phyllosphere. Predictive metagenomics revealed that the SA-mediated microbiome was enriched for antibiotic biosynthesis and the degradation of a diverse range of xenobiotics. Core taxa were predicted to be more motile, biofilm-forming and were enriched for traits associated with microbe-microbe communication; offering potential mechanistic explanation of their success despite SA-mediated phyllospheric disturbance.