bluuebunny/crossref_metadata_2025 huggingface dataset:
The Super Thermal Conductivity Model for High-Temperature Heat Pipe Applied to Heat Pipe Cooled Reactor
Authors: Guo Yuchuan , Su Zilin , Li Zeguang , Wang Kan
Published: January 2022

Differing from the traditional Pressurized Water Reactor (PWR), heat pipe cooled reactor adopts the high-temperature heat pipes to transport fission heat generated in the reactor core. Therefore, the basis of coupling calculation on this type of reactor system is to have a suitable model for high-temperature heat pipe simulation. Not only is it required that this model can well describe the transient characteristics of heat pipe, but it should be simple enough to reduce the computational resource. In this paper, the super thermal conductivity model (STCM) for high-temperature heat pipe is proposed for this purpose. In this model, heat transport of vapor flow is simplified as high efficiency heat conductance. Combined with the network method, the evaporation rate, the condensation rate, and the flow rate in the wick region can be preliminarily obtained. Using recommended equations to calculate the heat transfer limitation, this model can realize the safety judgment of heat pipe. The heating system for high-temperature heat pipe is established to validate this model. The heating experiments with different heating powers is tested. Then, this model is applied on the numerical calculation of Kilowatt Reactor Using Stirling TechnologY (KRUSTY) reactor. In the steady state calculation, the results show that the temperature distribution on contact surface between fuel and heat pipe is nonuniform, which will lead to higher peak temperature and temperature difference for the reactor core. In the transient calculation, the load-following accident is chosen. Comparing with the experimental results, the applicability of the proposed model on heat pipe cooled reactor is verified. This model can be used for heat pipe cooled reactor simulation.
Non-Lethal Assessment of Potentially Toxic Elements Across Mammalian Trophic Levels in African Savannahs
Authors: Webster Andrea B. , Callealta Javier F. , Bennett Nigel C. , Ganswindt Andre
Published: January 2022

South Africa is one of the most diverse countries in the world but the increase in agricultural, industrial and technological development to meet the needs of the growing human population has led to increased amounts of potentially toxic elements (PTEs) and other chemicals in the environment. As regional and global environmental processes influence local conditions to differing degrees, all organisms within a specific environment are exposed to highly complex, ill-defined PTE and chemical mixtures. Differences in feeding strategies within and between vertebrate trophic levels are likely to influence the degree to which individuals may be exposed to and affected by PTE presence. Using vertebrate faeces as a biological matrix, we investigate and compare quantitative differences in PTE concentrations in herbivorous, omnivorous and carnivorous terrestrial vertebrates from two protected areas in South African savannah. Of the eleven PTEs assessed [aluminium (Al), arsenic (As), barium (Ba), cadmium (Cd), chromium (Cr), mercury (Hg), lead (Pb), antimony (Sb), tin (Sn), strontium (Sr), and vanadium (V)], the highest concentrations of Al, As, Cr, Pb, Sn, and V were found in carnivores. General patterns were evident between groups at each site for specific elements, but absolute values for the same elements were site-specific. This is the first study to non-invasively examine and compare PTE concentrations in a variety of free-ranging mammalian wildlife occupying different trophic levels within South African protected areas. Our results confirm that all individuals across trophic levels within these sites are exposed to multiple and varied PTE mixtures on a continuous basis. Whether PTEs at these concentrations cause synergistic or antagonistic disruption of physiological and biological systems alone or in combination in free-ranging African wildlife species is still unclear and requires further investigation.
Random Forest Analysis of Impact of Abiotic Factors on Culex pipiens and Culex quinquefasciatus Occurrence
Authors: Arora Arinder K. , Sim Cheolho , Severson David W. , Kang David S.
Published: January 2022

The Culex pipiens complex of mosquitoes are significant vectors of several pathogens resulting in infectious human diseases in North America, including but not limited to West Nile encephalitis, Rift Valley Fever, and Lymphatic filariasis. Among this complex are C. pipiens form pipiens and Culex quinquefasciatus. While morphologically similar, the mosquitoes exhibit unique life histories that suit them uniquely to divergent niches, wherein C. pipiens can thrive despite the cold winters of the northern United States and C. quinquefasciatus is able to survive periods of drought typical in the southern states. Here, Random Forests machine-learning algorithms were employed to model and explore which environmental parameters best explain mosquito occurrence in historical trapping data across the continental United States of America, and test correlation with abundance data. The models explained between 71 and 97% of the presence or absence of the two mosquitoes based on historical climatic data. The results of this study will improve vector management programs by explaining which environmental variables will provide the most accurate predictions of mosquito presence at a given site.
Methyl Salicylate Can Benefit Ornamental Pest Control, and Does Not Alter Per Capita Predator Consumption at Close-Range
Authors: Lee Jana C. , Flores Salvador M. , Velasco Graham Katerina , Skillman Victoria P.
Published: January 2022

Methyl salicylate (MeSA) is an herbivore-induced plant volatile widely tested for attracting natural enemies for pest control. MeSA is commercially sold as slow-release lures or as a spray. While MeSA application has increased the abundance of natural enemies in numerous food crops, its ability to reduce pests for crop protection is not as frequently demonstrated. Our first objective was to test MeSA lures in ornamental fields where few studies have been done, and monitor natural enemies, pests, and crop protection. A 2-year study in spruce container yards revealed more aphid parasitoids (Pseudopraon sp.), fewer aphids (Mindarus obliquus) on shoot tips, and less shoot tip damage in MeSA plots during the first year. A 2-year study in red maple fields revealed more predatory lady beetles and rove beetles, and parasitic Ceraphronidae, Diapriidae, and Chalcidoidea in one or both years with MeSA. Fewer pest thrips were also captured in MeSA plots, though it is not clear whether this was due to enhanced predation or reduced colonization. Maple growth as measured by stem diameter change did not differ with MeSA use. A 2-year study examining predation on sentinel Halyomorpha halys eggs in various mature ornamental stock blocks found no increase in predation except for 1 month, though green lacewings, lady beetles, and predatory thrips occurred more in MeSA plots in the first year. While MeSA is expected to enhance biological control by herding in natural enemies, the impacts that applied volatiles have on predator efficiency is mostly unknown. Thus, our second objective examined how volatiles would impact feeding rates at close-range. Adult carabid Pterostichus melanarius, adult coccinellids Coccinella septempunctata and Harmonia axyridis, and larval lacewing Chrysoperla rufilabris consumed their prey at similar rates in the presence/absence of MeSA when food was presented directly in a 28 cm2 or 30 ml arena, or when foraging in a 520 cm2 outdoor soil arena or 946 ml arena with aphids on leaves.
Human Immune System Diseasome Networks and Female Oviductal Microenvironment: New Horizons to be Discovered
Authors: Taraschi Angela , Cimini Costanza , Colosimo Alessia , Ramal-Sanchez Marina , Moussa Fadl , Mokh Samia , Valbonetti Luca , Capacchietti Giulia , Tagaram Israiel , Bernabò Nicola , Barboni Barbara
Published: January 2022

Human hypofertility and infertility are two worldwide conditions experiencing nowadays an alarming increase due to a complex ensemble of events. The immune system has been suggested as one of the responsible for some of the etiopathogenic mechanisms involved in these conditions. To shed some light into the strong correlation between the reproductive and immune system, as can be inferred by the several and valuable manuscripts published to date, here we built a network using a useful bioinformatic tool (DisGeNET), in which the key genes involved in the sperm-oviduct interaction were linked. This constitutes an important event related with Human fertility since this interaction, and specially the spermatozoa, represents a not-self entity immunotolerated by the female. As a result, we discovered that some proteins involved in the sperm-oviduct interaction are implicated in several immune system diseases while, at the same time, some immune system diseases could interfere by using different pathways with the reproduction process. The data presented here could be of great importance to understand the involvement of the immune system in fertility reduction in Humans, setting the basis for potential immune therapeutic tools in the near future.
Integration of Transcriptome and Proteome in Lymph Nodes Reveal the Different Immune Responses to PRRSV Between PRRSV-Resistant Tongcheng Pigs and PRRSV-Susceptible Large White Pigs
Authors: Liang Wan , Meng Xiangge , Zhen Yueran , Zhang Yu , Hu Xueying , Zhang Qingde , Zhou Xiang , Liu Bang
Published: January 2022

Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease that seriously affects the swine industry worldwide. Understanding the interaction between the host immune response and PRRS virus (PRRSV) can provide insight into the PRRSV pathogenesis, as well as potential clues to control PRRSV infection. Here, we examined the transcriptome and proteome differences of lymph nodes between PRRSV-resistant Tongcheng (TC) pigs and PRRSV-susceptible Large White (LW) pigs in response to PRRSV infection. 2245 and 1839 differentially expressed genes (DEGs) were detected in TC and LW pigs upon PRRSV infection, respectively. Transcriptome analysis revealed genetic differences in antigen presentation and metabolism between TC pigs and LW pigs, which may lead to different immune responses to PRRSV infection. Furthermore, 678 and 1000 differentially expressed proteins (DEPs) were identified in TC and LW pigs, and DEPs were mainly enriched in the metabolism pathways. Integrated analysis of transcriptome and proteome datasets revealed antigen recognition capacity, immune activation, cell cycles, and cell metabolism are important for PRRSV clearance. In conclusion, this study provides important resources on transcriptomic and proteomic levels in lymph nodes for further revealing the interaction between the host immune response and PRRSV, which would give us new insight into molecular mechanisms related to genetic complexity against PRRSV.
Machine Learning: A New Prospect in Multi-Omics Data Analysis of Cancer
Authors: Arjmand Babak , Hamidpour Shayesteh Kokabi , Tayanloo-Beik Akram , Goodarzi Parisa , Aghayan Hamid Reza , Adibi Hossein , Larijani Bagher
Published: January 2022

Cancer is defined as a large group of diseases that is associated with abnormal cell growth, uncontrollable cell division, and may tend to impinge on other tissues of the body by different mechanisms through metastasis. What makes cancer so important is that the cancer incidence rate is growing worldwide which can have major health, economic, and even social impacts on both patients and the governments. Thereby, the early cancer prognosis, diagnosis, and treatment can play a crucial role at the front line of combating cancer. The onset and progression of cancer can occur under the influence of complicated mechanisms and some alterations in the level of genome, proteome, transcriptome, metabolome etc. Consequently, the advent of omics science and its broad research branches (such as genomics, proteomics, transcriptomics, metabolomics, and so forth) as revolutionary biological approaches have opened new doors to the comprehensive perception of the cancer landscape. Due to the complexities of the formation and development of cancer, the study of mechanisms underlying cancer has gone beyond just one field of the omics arena. Therefore, making a connection between the resultant data from different branches of omics science and examining them in a multi-omics field can pave the way for facilitating the discovery of novel prognostic, diagnostic, and therapeutic approaches. As the volume and complexity of data from the omics studies in cancer are increasing dramatically, the use of leading-edge technologies such as machine learning can have a promising role in the assessments of cancer research resultant data. Machine learning is categorized as a subset of artificial intelligence which aims to data parsing, classification, and data pattern identification by applying statistical methods and algorithms. This acquired knowledge subsequently allows computers to learn and improve accurate predictions through experiences from data processing. In this context, the application of machine learning, as a novel computational technology offers new opportunities for achieving in-depth knowledge of cancer by analysis of resultant data from multi-omics studies. Therefore, it can be concluded that the use of artificial intelligence technologies such as machine learning can have revolutionary roles in the fight against cancer.
Dominant Antiviral CD8+ T Cell Responses Empower Prophylactic Antibody-Eliciting Vaccines Against Cytomegalovirus
Authors: Pardieck Iris N. , van Duikeren Suzanne , Veerkamp Dominique M. B. , Brasem Dena J. , Redeker Anke , van Bergen Jeroen , Han Wanda , Ossendorp Ferry , Zondag Gerben , Arens Ramon
Published: January 2022

Human cytomegalovirus (HCMV) is an ubiquitous herpesvirus that can cause serious morbidity and mortality in immunocompromised or immune-immature individuals. A vaccine that induces immunity to CMV in these target populations is therefore highly needed. Previous attempts to generate efficacious CMV vaccines primarily focused on the induction of humoral immunity by eliciting neutralizing antibodies. Current insights encourage that a protective immune response to HCMV might benefit from the induction of virus-specific T cells. Whether addition of antiviral T cell responses enhances the protection by antibody-eliciting vaccines is however unclear. Here, we assessed this query in mouse CMV (MCMV) infection models by developing synthetic vaccines with humoral immunity potential, and deliberately adding antiviral CD8+ T cells. To induce antibodies against MCMV, we developed a DNA vaccine encoding either full-length, membrane bound glycoprotein B (gB) or a secreted variant lacking the transmembrane and intracellular domain (secreted (s)gB). Intradermal immunization with an increasing dose schedule of sgB and booster immunization provided robust viral-specific IgG responses and viral control. Combined vaccination of the sgB DNA vaccine with synthetic long peptides (SLP)-vaccines encoding MHC class I-restricted CMV epitopes, which elicit exclusively CD8+ T cell responses, significantly enhanced antiviral immunity. Thus, the combination of antibody and CD8+ T cell-eliciting vaccines provides a collaborative improvement of humoral and cellular immunity enabling enhanced protection against CMV.
Rexinoids Modulate Effector T Cell Expression of Mucosal Homing Markers CCR9 and α4β7 Integrin and Direct Their Migration In Vitro
Authors: Manhas Kavita R. , Marshall Pamela A. , Wagner Carl E. , Jurutka Peter W. , Mancenido Michelle V. , Debray Hannah Z. , Blattman Joseph N.
Published: January 2022

Altering T cell trafficking to mucosal regions can enhance immune responses towards pathogenic infections and cancers at these sites, leading to better outcomes. All-trans-retinoic acid (ATRA) promotes T cell migration to mucosal surfaces by inducing transcription of the mucosal-homing receptors CCR9 and α4β7 via binding to retinoic acid receptors (RARs), which heterodimerize with retinoid X receptors (RXRs) to function. However, the unstable nature and toxicity of ATRA limit its use as a widespread treatment modality for mucosal diseases. Therefore, identifying alternatives that could reduce or eliminate the use of ATRA are needed. Rexinoids are synthetically derived compounds structurally similar to ATRA. Originally named for their ability to bind RXRs, rexinoids can enhance RAR-mediated gene transcription. Furthermore, rexinoids are more stable than ATRA and possess an improved safety profile, making them attractive candidates for use in clinical settings. Here we show that select novel rexinoids act as ATRA mimics, as they cause increased CCR9 and α4β7 expression and enhanced migration to the CCR9 ligand, CCL25 in vitro, even in the absence of ATRA. Conversely, other rexinoids act synergistically with ATRA, as culturing cells with suboptimal doses of both compounds resulted in CCR9 expression and migration to CCL25. Overall, our findings show that rexinoids can be used independently or synergistically with ATRA to promote mucosal homing of T cells in vitro, and lends support for the prospective clinical use of these compounds in immunotherapeutic approaches for pathogenic infections or cancers at mucosal surfaces.
Identification of a Novel Nomogram to Predict Progression Based on the Circadian Clock and Insights Into the Tumor Immune Microenvironment in Prostate Cancer
Authors: Feng Dechao , Xiong Qiao , Zhang Facai , Shi Xu , Xu Hang , Wei Wuran , Ai Jianzhong , Yang Lu
Published: January 2022

Background

Currently, the impact of the circadian rhythm on the tumorigenesis and progression of prostate cancer (PCA) has yet to be understood. In this study, we first established a novel nomogram to predict PCA progression based on circadian clock (CIC)-related genes and provided insights into the tumor immune microenvironment.

Methods

The TCGA and Genecards databases were used to identify potential candidate genes. Lasso and Cox regression analyses were applied to develop a CIC-related gene signature. The tumor immune microenvironment was evaluated through appropriate statistical methods and the GSCALite database.

Results

Ten genes were identified to construct a gene signature to predict progression probability for patients with PCA. Patients with high-risk scores were more prone to progress than those with low-risk scores (hazard ratio (HR): 4.11, 95% CI: 2.66-6.37; risk score cut-off: 1.194). CLOCK, PER (1, 2, 3), CRY2, NPAS2, RORA, and ARNTL showed a higher correlation with anti-oncogenes, while CSNK1D and CSNK1E presented a greater relationship with oncogenes. Overall, patients with higher risk scores showed lower mRNA expression of PER1, PER2, and CRY2 and higher expression of CSNK1E. In general, tumor samples presented higher infiltration levels of macrophages, T cells and myeloid dendritic cells than normal samples. In addition, tumor samples had higher immune scores, lower stroma scores and lower microenvironment scores than normal samples. Notably, patients with higher risk scores were associated with significantly lower levels of neutrophils, NK cells, T helper type 1, and mast cells. There was a positive correlation between the risk score and the tumor mutation burden (TMB) score, and patients with higher TMB scores were more prone to progress than those with lower TMB scores. Likewise, we observed similar results regarding the correlation between the microsatellite instability (MSI) score and the risk score and the impact of the MSI score on the progression-free interval. We observed that anti-oncogenes presented a significantly positive correlation with PD-L1, PD-L2, TIGIT and SIGLEC15, especially PD-L2.

Conclusion

We identified ten prognosis-related genes as a promising tool for risk stratification in PCA patients from the fresh perspective of CIC.
Molecular Identification of Nocardia seriolae and Comparative Analysis of Spleen Transcriptomes of Hybrid Snakehead (Channa maculata Female × Channa argus Male) With Nocardiosis Disease
Authors: Zhang Ning , Zhang Hairui , Dong Zhongdian , Wang Wei
Published: January 2022

Hybrid snakehead (Channa maculata female × Channa argus male) is a new freshwater aquaculture fish species in southern China. During intensive aquaculture, hybrid snakeheads are often infected by Nocardia seriolae. In this study, hybrid snakehead infected suspiciously by N. seriolae in an artificial breeding pond were examined. Diseased hybrid snakeheads swam slowly without food intake, and the clinical symptoms included skin wound, anal swelling and ascites, and white granulomatous in liver, spleen, and kidney of fish. Through bacterial isolation, 16S rDNA sequencing, fluorescence in situ hybridization (FISH) and artificial infection experiment, the pathogen was identified as N. seriolae. Furthermore, the spleen samples from diseased and healthy male hybrid snakeheads in the same pond were used for RNA-Seq analysis. A total of 3,512 unique transcripts (unigenes) were identified as differentially expressed genes (DEGs), and 1,886 of them were up-regulated in diseased fish. The expression patterns of 20 DEGs were verified by quantitative polymerase chain reaction (qPCR). Several immune-related pathways and many immune-related genes were identified. qPCR results showed that the expression patterns of immune-related genes in the liver and kidney of diseased fish were comparable to that in the spleen. This study provides deep-sequencing data of hybrid snakehead spleen and will help understand the immune response of hybrid snakehead to N. seriolae. It is also helpful for the biomarker screening of fish-borne Nocardia spp. and the breeding of nocardiosis-resistant fish species.
Mast Cell Chymase/Mcpt4 Suppresses the Host Immune Response to Plasmodium yoelii, Limits Malaria-Associated Disruption of Intestinal Barrier Integrity and Reduces Parasite Transmission to Anopheles stephensi
Authors: Céspedes Nora , Donnelly Erinn L. , Lowder Casey , Hansten Gretchen , Wagers Delaney , Briggs Anna M. , Schauer Joseph , Haapanen Lori , Åbrink Magnus , Van de Water Judy , Luckhart Shirley
Published: January 2022

An increase in mast cells (MCs) and MCs mediators has been observed in malaria-associated bacteremia, however, the role of these granulocytes in malarial immunity is poorly understood. Herein, we studied the role of mouse MC protease (Mcpt) 4, an ortholog of human MC chymase, in malaria-induced bacteremia usingMcpt4knockout (Mcpt4-/-) mice andMcpt4+/+C57BL/6J controls, and the non-lethal mouse parasitePlasmodium yoelii yoelii17XNL. Significantly lower parasitemia was observed inMcpt4-/-mice compared withMcpt4+/+controls by day 10 post infection (PI). Although bacterial 16S DNA levels in blood were not different between groups, increased intestinal permeability to FITC-dextran and altered ileal adherens junction E-cadherin were observed inMcpt4-/-mice. Relative to infectedMcpt4+/+mice, ileal MC accumulation inMcpt4-/-mice occurred two days earlier and IgE levels were higher by days 8-10 PI. Increased levels of circulating myeloperoxidase were observed at 6 and 10 days PI inMcpt4+/+but notMcpt4-/-mice, affirming a role for neutrophil activation that was not predictive of parasitemia or bacterial 16S copies in blood. In contrast, early increased plasma levels of TNF-α, IL-12p40 and IL-3 were observed inMcpt4-/-mice, while levels of IL-2, IL-10 and MIP1β (CCL4) were increased over the same period inMcpt4+/+mice, suggesting that the host response to infection was skewed toward a type-1 immune response inMcpt4-/-mice and type-2 response inMcpt4+/+mice. Spearman analysis revealed an early (day 4 PI) correlation ofMcpt4-/-parasitemia with TNF-α and IFN-γ, inflammatory cytokines known for their roles in pathogen clearance, a pattern that was observed inMcpt4+/+mice much later (day 10 PI). Transmission success ofP. y. yoelii17XNL toAnopheles stephensiwas significantly higher from infectedMcpt4-/-mice compared with infectedMcpt4+/+mice, suggesting that Mcpt4 also impacts transmissibility of sexual stage parasites. Together, these results suggest that early MCs activation and release of Mcpt4 suppresses the host immune response toP. y. yoelii17XNL, perhapsviadegradation of TNF-α and promotion of a type-2 immune response that concordantly protects epithelial barrier integrity, while limiting the systemic response to bacteremia and parasite transmissibility.
Identifying a Novel Defined Pyroptosis-Associated Long Noncoding RNA Signature Contributes to Predicting Prognosis and Tumor Microenvironment of Bladder Cancer
Authors: Lu Hongcheng , Wu Jiajin , Liang Linghui , Wang Xinwei , Cai Hongzhou
Published: January 2022

Background

Bladder cancer (BLCA) is a common malignant tumor of the urinary tract, which is the sixth most common cancer among men. Numerous studies suggested that pyroptosis and long noncoding RNAs (lncRNAs) played an essential role in the development of cancers. However, the role of pyroptosis-related lncRNAs in BLCA and their prognostic value are still unclear.

Methods

In this study, we constructed a signature model through least absolute shrinkage and selection operator (LASSO) Cox regression analysis and Cox univariate analysis based on The Cancer Genome Atlas (TCGA) database. The expression of 12 pyroptosis-related lncRNAs was also confirmed by qRT-PCR in BLCA cell lines. TIMER, XCELL, QUANTISEQ, MCPCOUNTER, EPIC, and CIBERSORT R script were applied to quantify the relative proportions of infiltrating immune cells. Correlation coefficients were computed by Spearman analyses. The Kaplan–Meier method, Cox regression model, and log-rank tests were used to evaluate the prognostic value. The R package of pRRophetic was used to predict IC50 of common chemotherapeutic agents.

Results

A total of 12 pyroptosis-related lncRNAs with great prognosis value were identified. The expression was investigated by qRT-PCR in four BLCA cell lines. Then, 126 cases were identified as high-risk group, and 277 cases were identified as low-risk group based on the cutoff point. Patients in the low-risk group showed a significant survival advantage. Furthermore, we found that clinical features were significantly related to the risk score. As well, based on the C-index values, a nomogram was constructed. The gene set enrichment analysis (GSEA) results showed that mitogen-activated protein kinase (MAPK) signaling, transforming growth factor (TGF)-β signaling, and WNT signaling were with important significance in the high-risk group. Moreover, we found that riskscore was positively correlated with M0 macrophages and M2 macrophages.

Conclusions

In conclusion, our study indicated that pyroptosis is closely connected to BLCA. The riskscore generated from the expression of 12 pyroptosis-related lncRNAs was evaluated by various clinical features including survival status, tumor microenvironment, clinicopathological characteristic, and chemotherapy. It may offer a significant basis for future studies.
Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells From HIV+ Controllers and ART-Suppressed Individuals
Authors: George Ashley F. , Luo Xiaoyu , Neidleman Jason , Hoh Rebecca , Vohra Poonam , Thomas Reuben , Shin Min-Gyoung , Lee Madeline J. , Blish Catherine A. , Deeks Steven G. , Greene Warner C. , Lee Sulggi A. , Roan Nadia R.
Published: January 2022

T and natural killer (NK) cells are effector cells with key roles in anti-HIV immunity, including in lymphoid tissues, the major site of HIV persistence. However, little is known about the features of these effector cells from people living with HIV (PLWH), particularly from those who initiated antiretroviral therapy (ART) during acute infection. Our study design was to use 42-parameter CyTOF to conduct deep phenotyping of paired blood- and lymph node (LN)-derived T and NK cells from three groups of HIV+ aviremic individuals: elite controllers (N = 5), and ART-suppressed individuals who had started therapy during chronic (N = 6) vs. acute infection (N = 8), the latter of which is associated with better outcomes. We found that acute-treated individuals are enriched for specific subsets of T and NK cells, including blood-derived CD56-CD16+ NK cells previously associated with HIV control, and LN-derived CD4+ T follicular helper cells with heightened expansion potential. An in-depth comparison of the features of the cells from blood vs. LNs of individuals from our cohort revealed that T cells from blood were more activated than those from LNs. By contrast, LNs were enriched for follicle-homing CXCR5+ CD8+ T cells, which expressed increased levels of inhibitory receptors and markers of survival and proliferation as compared to their CXCR5- counterparts. In addition, a subset of memory-like CD56brightTCF1+ NK cells was enriched in LNs relative to blood. These results together suggest unique T and NK cell features in acute-treated individuals, and highlight the importance of examining effector cells not only in blood but also the lymphoid tissue compartment, where the reservoir mostly persists, and where these cells take on distinct phenotypic features.
PTPN2, A Key Predictor of Prognosis for Pancreatic Adenocarcinoma, Significantly Regulates Cell Cycles, Apoptosis, and Metastasis
Authors: Kuang Wenbin , Wang Xiao , Ding Jiayu , Li Jiaxing , Ji Minghui , Chen Weijiao , Wang Liping , Yang Peng
Published: January 2022

Objective

This study conducted a comprehensive analysis of the members of the PTPN family and emphasized the key role of PTPN2 as a potential therapeutic target and diagnostic biomarker in improving the survival rate of PAAD.

Method

Oncomine was used to analyze the pan-cancer expression of the PTPN gene family. The Cancer Genome Atlas (TCGA) data as well as Genotype-Tissue Expression (GTEx) data were downloaded to analyze the expression and prognosis of PTPNs. The diagnosis of PTPNs was evaluated by the experimental ROC curve. The protein-protein interaction (PPI) network was constructed by combining STRING and Cytoscape. The genes of 50 proteins most closely related to PTPN2 were screened and analyzed by GO and KEGG enrichment. The differentially expressed genes of PTPN2 were found by RNA sequencing, and GSEA enrichment analysis was carried out to find the downstream pathways and targets, which were verified by online tools and experiments. Finally, the relationship between PTPN2 and immune cell infiltration in PAAD, and the relationship with immune score and immune checkpoint were studied.

Result

The expression patterns and the prognostic value of multiple PTPNs in PAAD have been reported through bioinformatic analyzes. Among these members, PTPN2 is the most important prognostic signature that regulates the progression of PAAD by activating JAK-STAT signaling pathway. Comparison of two PAAD cell lines with normal pancreatic epithelial cell lines revealed that PTPN2 expression was up-regulated as a key regulator of PAAD, which was associated with poor prognosis. Knockdown of PTPN2 caused a profound decrease in PAAD cell growth, migration, invasion, and induced PAAD cell cycle and apoptosis. In addition, we conducted a series of enrichment analyses to investigate the PTPN2-binding proteins and the PTPN2 expression-correlated genes. We suggest that STAT1 and EGFR are the key factors to regulate PTPN2, which are involved in the progression of PAAD. Meanwhile, the silencing of PTPN2 induced the repression of STAT1 and EGFR expression.

Conclusion

These findings provide a comprehensive analysis of the PTPN family members, and for PAAD, they also demonstrate that PTPN2 is a diagnostic biomarker and a therapeutic target.
Characterization of Pipefish Immune Cell Populations Through Single-Cell Transcriptomics
Authors: Parker Jamie , Guslund Naomi Croft , Jentoft Sissel , Roth Olivia
Published: January 2022

Teleost adaptive immune systems have evolved with more flexibility than previously assumed. A particularly enigmatic system to address immune system modifications in the evolutionary past is represented by the Syngnathids, the family of pipefishes, seahorses and seadragons. These small fishes with their unique male pregnancy have lost the spleen as an important immune organ as well as a functional major histocompatibility class II (MHC II) pathway. How these evolutionary changes have impacted immune cell population dynamics have up to this point remained unexplored. Here, we present the first immune cell repertoire characterization of a syngnathid fish (Syngnathus typhle) using single-cell transcriptomics. Gene expression profiles of individual cells extracted from blood and head-kidney clustered in twelve putative cell populations with eight belonging to those with immune function. Upregulated cell marker genes identified in humans and teleosts were used to define cell clusters. While the suggested loss of CD4+ T-cells accompanied the loss of the MHC II pathway was supported, the upregulation of specific subtype markers within the T-cell cluster indicates subpopulations of regulatory T-cells (il2rb) and cytotoxic T-cells (gzma). Utilizing single-cell RNA sequencing this report is the first to characterize immune cell populations in syngnathids and provides a valuable foundation for future cellular classification and experimental work within the lineage.
The Splenic Marginal Zone in Children Is Characterized by a Subpopulation of CD27-Negative, Lowly IGHV-Mutated B Cells
Authors: Kibler Artur , Budeus Bettina , Küppers Ralf , Seifert Marc
Published: January 2022

Young children and older adults suffer from enhanced susceptibility to infections with blood-borne pathogens. An essential step towards immunity is the establishment of a splenic marginal zone (sMZ), which is immature at below 2 years of age. At approximately 5 years of age, an adult level of protection is reached but wanes again in older adults. Although the infant sMZ is thought to contain mostly naïve B cells, memory B cells are recruited to and recirculate from the sMZ throughout life, and class-switched sMZ B cells dominate in older adults. For a better resolution of naïve versus memory B-cell subset accumulation in the sMZ, we performed a single cell-based gene expression analysis of (CD21highIgMhigh) sMZ B cells among five healthy donors (age 3 to 48 years) and validated the sMZ B-cell subset composition by flow cytometry of 147 spleen biopsies (age 0 to 82 years). We identified a major sMZ B-cell subpopulation, which is abundant at birth but decreases with age. These cells lack CD27 expression but carry a weak-to-intermediate memory B-cell signature. These CD27negsMZ B cells are either IGHV-unmutated or carry only a few IGHV mutations early in life but show average memory B-cell IGHV mutation frequencies (>3%) in adults. The activation and proliferation potential of CD27negsMZ B cells is significantly above that of non-sMZ B cells already in children. Our study suggests that the human sMZ B-cell pool changes with age, encompassing a major population of lowly Ig-mutated CD27neg but antigen-experienced B cells early in life.
Train the Trainer: Hematopoietic Stem Cell Control of Trained Immunity
Authors: De Zuani Marco , Frič Jan
Published: January 2022

Recent evidence shows that innate immune cells, in addition to B and T cells, can retain immunological memory of their encounters and afford long-term resistance against infections in a process known as ‘trained immunity’. However, the duration of the unspecific protection observed in vivo is poorly compatible with the average lifespan of innate immune cells, suggesting the involvement of long-lived cells. Accordingly, recent studies demonstrate that hematopoietic stem and progenitor cells (HSPCs) lay at the foundation of trained immunity, retaining immunological memory of infections and giving rise to a “trained” myeloid progeny for a long time. In this review, we discuss the research demonstrating the involvement of HSPCs in the onset of long-lasting trained immunity. We highlight the roles of specific cytokines and Toll-like receptor ligands in influencing HSPC memory phenotypes and the molecular mechanisms underlying trained immunity HSPCs. Finally, we discuss the potential benefits and drawbacks of the long-lasting trained immune responses, and describe the challenges that the field is facing.
Stemness Refines the Classification of Colorectal Cancer With Stratified Prognosis, Multi-Omics Landscape, Potential Mechanisms, and Treatment Options
Authors: Liu Zaoqu , Xu Hui , Weng Siyuan , Ren Yuqing , Han Xinwei
Published: January 2022

Background

Stemness refers to the capacities of self-renewal and repopulation, which contributes to the progression, relapse, and drug resistance of colorectal cancer (CRC). Mounting evidence has established the links between cancer stemness and intratumoral heterogeneity across cancer. Currently, the intertumoral heterogeneity of cancer stemness remains elusive in CRC.

Methods

This study enrolled four CRC datasets, two immunotherapy datasets, and a clinical in-house cohort. Non-negative matrix factorization (NMF) was performed to decipher the heterogeneity of cancer stemness. Multiple machine learning algorithms were applied to develop a nine-gene stemness cluster predictor. The clinical outcomes, multi-omics landscape, potential mechanisms, and immune features of the stemness clusters were further explored.

Results

Based on 26 published stemness signatures derived by alternative approaches, we decipher two heterogeneous clusters, low stemness cluster 1 (C1) and high stemness cluster 2 (C2). C2 possessed a higher proportion of advanced tumors and displayed worse overall survival and relapse-free survival compared with C1. The MSI-H and CMS1 tumors tended to enrich in C1, and the mesenchymal subtype CMS4 was the prevalent subtype of C2. Subsequently, we developed a nine-gene stemness cluster predictor, which robustly validated and reproduced our stemness clusters in three independent datasets and an in-house cohort. C1 also displayed a generally superior mutational burden, and C2 possessed a higher burden of copy number deletion. Further investigations suggested that C1 enriched numerous proliferation-related biological processes and abundant immune infiltration, while C2 was significantly associated with mesenchyme development and differentiation. Given results derived from three algorithms and two immunotherapeutic cohorts, we observed C1 could benefit more from immunotherapy. For patients with C2, we constructed a ridge regression model and further identified nine latent therapeutic agents, which might improve their clinical outcomes.

Conclusions

This study proposed two stemness clusters with stratified prognosis, multi-omics landscape, potential mechanisms, and treatment options. Current work not only provided new insights into the heterogeneity of cancer stemness, but also shed light on optimizing decision-making in immunotherapy and chemotherapy.
Long-Term Kinetics of SARS-CoV-2 Antibodies and Impact of Inactivated Vaccine on SARS-CoV-2 Antibodies Based on a COVID-19 Patients Cohort
Authors: Zhang Shihan , Xu Ke , Li Chuchu , Zhou Lu , Kong Xiaoxiao , Peng Jiefu , Zhu Fengcai , Bao Changjun , Jin Hui , Gao Qiang , Zhao Xing , Zhu Liguo
Published: January 2022

Background

Understanding the long-term kinetic characteristics of SARS-CoV-2 antibodies and the impact of inactivated vaccines on SARS-CoV-2 antibodies in convalescent patients can provide information for developing and improving vaccination strategies in such populations.

Methods

In this cohort, 402 convalescent patients who tested positive for SARS-CoV-2 by RT-PCR from 1 January to 22 June 2020 in Jiangsu, China, were enrolled. The epidemiological data included demographics, symptom onset, and vaccination history. Blood samples were collected and tested for antibody levels of specific IgG, IgM, RBD-IgG, S-IgG, and neutralizing antibodies using a the commercial magnetic chemiluminescence enzyme immunoassay.

Results

The median follow-up time after symptom onset was 15.6 months (IQR, 14.6 to 15.8). Of the 402 convalescent patients, 44 (13.84%) received an inactivated vaccine against COVID-19. A total of 255 (80.19%) patients were IgG-positive and 65 (20.44%) were IgM-positive. The neutralizing antibody was 83.02%. Compared with non-vaccinated individuals, the IgG antibody levels in vaccinated people were higher (P=0.007). Similarly, antibody levels for RBD-IgG, S-IgG, and neutralizing antibodies were all highly increased in vaccinated individuals (P<0.05). IgG levels were significantly higher after vaccination than before vaccination in the same population. IgG levels in those who received ‘single dose and ≥14d’ were similar to those with two doses (P>0.05). Similar conclusions were drawn for RBD-IgG and the neutralizing antibody.

Conclusion

15.6 months after symptom onset, the majority of participants remained positive for serum-specific IgG, RBD-IgG, S-IgG, and neutralizing antibodies. For convalescent patients, a single dose of inactivated vaccine against COVID-19 can further boost antibody titres.
Genetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy
Authors: Rangel Roberto , Pickering Curtis R. , Sikora Andrew G. , Spiotto Michael T.
Published: January 2022

Oral premalignant lesions (OPLs) are the precursors to oral cavity cancers, and have variable rates of progression to invasive disease. As an intermediate state, OPLs have acquired a subset of the genomic alterations while arising in an oral inflammatory environment. These specific genomic changes may facilitate the transition to an immune microenvironment that permits malignant transformation. Here, we will discuss mechanisms by which OPLs develop an immunosuppressive microenvironment that facilitates progression to invasive cancer. We will describe how genomic alterations and immune microenvironmental changes co-evolve and cooperate to promote OSCC progression. Finally, we will describe how these immune microenvironmental changes provide specific and unique evolutionary vulnerabilities for targeted therapies. Therefore, understanding the genomic changes that drive immunosuppressive microenvironments may eventually translate into novel biomarker and/or therapeutic approaches to limit the progression of OPLs to potential lethal oral cancers.
Population Density, Reproduction Cycle and Nutritional Value of Sphaerechinus granularis (Echinodermata: Echinoidea) in an Oceanic Insular Ecosystem
Authors: Lourenço Sílvia , José Ricardo , Neves Pedro , Góis André , Cordeiro Nereida , Andrade Carlos , Ribeiro Cláudia
Published: January 2022

Sea urchins play an important role in island coastal ecosystems as keystone species and as potential resources for harvesting and aquaculture. In Southern Europe, the most valuable and harvested species is the European purple sea urchin Paracentrotus lividus, but there is a growing interest to explore other edible species like the blunt sea urchin Sphaerechinus granularis. The echinoderms biodiversity of Madeira archipelago was previously described, but their local habitat, population densities and size distribution, important to establish their harvest and aquaculture potential, are poorly known. The present study aimed to evaluate S. granularis population in the oligotrophic and narrow insular shelf of Madeira archipelago, mainly regarding its habitat, densities, reproduction season and roe marketable characteristics. Sphaerechinus granularis was found in low densities (0.01 ind./m2) from shallow to deep reefs (5–30 m). The highest densities occurred in shallow waters and breakwaters in association to encrusting algae, turf and erect brown macroalgae. Here, the low primary productivity ecosystem influenced the long reproductive season of the local population. This population showed a relatively high gonadosomatic index (maximum GI of 8), high gonad weight (5.00–12.19 g) with high proportion of bright yellow and orange gonads (37.5–60%) between February and November. Additionally, the high level of total carotenoids, the high PUFA (particularly EPA) content, and the ratio n-6/n-3 close to one support the high nutritional value of S. granularis roe. The trend of incremental GI between September and November and the increasing content of PUFA in autumn suggests this could be the preferential harvesting season. This information is key to evaluate a sustainable exploitation of this living marine resource.
Seasonal Variability of the Carbonate System and Air–Sea CO2 Flux in the Outer Changjiang Estuary, East China Sea
Authors: Liu Jing , Bellerby Richard G. J. , Li Xiaoshuang , Yang Anqiang
Published: January 2022

Three field surveys were conducted in the outer Changjiang Estuary on the inner shelf of the East China Sea in March, July, and October, 2018. Observations of total-scale pH (pHT), total alkalinity (AT), and calculated total dissolved inorganic carbon (CT), the partial pressure of CO2 (pCO2), and the air–sea CO2 exchange flux (FCO2) were studied in the surface waters. The results showed that the Changjiang Diluted Water (CDW) area was a source of atmospheric CO2 in July and October (4.97 and 8.67 mmol CO2/m2/day, respectively). The oversaturation of CO2 was mainly ascribed to the respiration of terrestrial organic and inorganic materials sourced from the Changjiang River discharge, overwhelming the CO2 uptake due to primary productivity despite the high phytoplankton biomass in summer. The air–sea CO2 flux was greater in October than in July in the CDW, which is attributed to the increasing wind speed. In contrast, the Yellow Sea Water (YSW) and the East China Sea Shelf Water (ECSSW) were a weak CO2 sink in March (–0.71 and –2.86 mmol CO2/m2/day, respectively) and July (–1.28 mmol CO2/m2/day in the ECSSW) following the CO2 uptake of phytoplankton production, however, they were a CO2 source by October (3.30 mmol CO2/m2/day in the YSW and 1.18 mmol CO2/m2/day in the ECSSW). The cooling effect during the cold season reduced the sea surface pCO2, resulting in a CO2 sink in the CDW, YSW, and ECSSW areas in March. However, the regions became a source of atmospheric CO2 in October, possibly driven by vertical mixing, which brought CT-enriched bottom water to the surface and increased the pCO2. The study region was a net CO2 sink in March and a net CO2 source in July and October with an average FCO2 of –1.25, 1.71, and 3.06 mmol CO2/m2/day, respectively.