bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR/Cas9-mediated gene mutation of EcIAG leads to sex reversal in the male ridgetail white prawn Exopalaemon carinicauda
Authors: Miao Miao , Li Shihao , Yuan Jianbo , Liu Peipei , Fang Xiaochen , Zhang Chengsong , Zhang Xiaojun , Li Fuhua
Published: November 2023

In the culture of crustaceans, most species show sexual dimorphism. Monosex culture is an effective approach to achieve high yield and economic value, especially for decapods of high value. Previous studies have developed some sex control strategies such as manual segregation, manipulation of male androgenic gland and knockdown of the male sexual differentiation switch gene encoding insulin-like androgenic gland hormone (IAG) in decapods. However, these methods could not generate hereditable changes. Genetic manipulation to achieve sex reversal individuals is absent up to now. In the present study, the gene encoding IAG (EcIAG) was identified in the ridgetail white prawn Exopalaemon carinicauda. Sequence analysis showed that EcIAG encoded conserved amino acid structure like IAGs in other decapod species. CRISPR/Cas9-mediated genome editing technology was used to knock out EcIAG. Two sgRNAs targeting the second exon of EcIAG were designed and microinjected into the prawn zygotes or the embryos at the first cleavage with commercial Cas9 protein. EcIAG in three genetic males was knocked out in both chromosome sets, which successfully generated sex reversal and phenotypic female characters. The results suggest that CRISPR/Cas9-mediated genome editing technology is an effective way to develop sex manipulation technology and contribute to monosex aquaculture in crustaceans.
Bile acid signalling and its role in anxiety disorders
Authors: Chen Simin , Shao Qi , Chen Jiayi , Lv Xinyi , Ji Jing , Liu Yan , Song Yuehan
Published: November 2023

Anxiety disorder is a prevalent neuropsychiatric disorder that afflicts 7.3%~28.0% of the world’s population. Bile acids are synthesized by hepatocytes and modulate metabolism via farnesoid X receptor (FXR), G protein-coupled receptor (TGR5), etc. These effects are not limited to the gastrointestinal tract but also extend to tissues and organs such as the brain, where they regulate emotional centers and nerves. A rise in serum bile acid levels can promote the interaction between central FXR and TGR5 across the blood-brain barrier or activate intestinal FXR and TGR5 to release fibroblast growth factor 19 (FGF19) and glucagon-like peptide-1 (GLP-1), respectively, which in turn, transmit signals to the brain via these indirect pathways. This review aimed to summarize advancements in the metabolism of bile acids and the physiological functions of their receptors in various tissues, with a specific focus on their regulatory roles in brain function. The contribution of bile acids to anxiety via sending signals to the brain via direct or indirect pathways was also discussed. Different bile acid ligands trigger distinct bile acid signaling cascades, producing diverse downstream effects, and these pathways may be involved in anxiety regulation. Future investigations from the perspective of bile acids are anticipated to lead to novel mechanistic insights and potential therapeutic targets for anxiety disorders.
The relationship between weight-adjusted-waist index and total bone mineral density in adults aged 20-59
Authors: Guo Meiqian , Lei Yi , Liu Xueqing , Li Xiang , Xu Yong , Zheng Donghui
Published: November 2023

Introduction

According to reports, obesity has a significant impact on bone health. And the weight-adjusted-waist index (WWI), superior to BMI and waist circumference (WC), is a new obesity indicator arising in recent years. This research investigated the relationship between WWI and total bone mineral density (BMD) for adults aged 20 to 59.

Methods

Using data from the 2011–2018 NHANES, we looked into the independent link between WWI and total BMD as well as its nonlinearity using weighted multiple linear regression and smooth curve fitting. Two-stage linear regression models were employed to calculate the threshold effects. There were additional subgroup analyses and testing for interactions.

Results

Multiple linear regression studies on a total of 10,372 individuals showed a significant inverse link between WWI and total BMD in adults between 20 and 59 [β = -0.04, 95% CI: (-0.04, -0.03), P<0.0001]. And smoking, race, and chronic kidney disease (CKD) had no significant effect on this negative connection (P for interaction >0.05). In addition, we found a nonlinear relationship between WWI and total BMD in diabetic and CKD patients, for which the saturation point was 11.38 cm/√kg in the CKD patient group and 10.29 cm/√kg in the diabetic patient group.

Conclusion

Our analysis demonstrated a significant inverse association between WWI and total BMD in adults aged 20-59.
Spatial disparities altered the determinants of biomass supply intention for clean energy: policy implications
Authors: Balagueman Rodrigue Ogoulonou , Assèdé Eméline Sêssi Pélagie , Moumouni-Moussa Ismail , Soumanou Abdul Aziz , Biaou Samadori Sorotori Honoré
Published: November 2023

Understanding the spatial variation of factors driving interest in bioenergy is important for designing effective energy policies. Although previous authors have broadly explored the determinants of biomass supply intentions in the field of bioenergy, the potential spatial variation of these factors has received limited consideration from bioenergy research. We performed a structural equation modeling based on the theory of planned behavior to investigate the impact of spatial disparities on factors determining people’s intentions to supply forestry residues for clean energy. Our data were generated through a survey of 247 participants randomly sampled from two contrasting geographic regions (north and south) of the Republic of Benin. We found that spatial disparities altered the effects of attitude and knowledge of renewable energy while income and perceived behavioral control exhibited consistent positive effects across geographical regions. Our findings imply that ignoring spatial disparities when analyzing bioenergy acceptance can lead to distorted inferences. These findings can be used as a baseline information by policymakers to develop region-specific actions for achieving local transition toward clean energy in the Republic of Benin.
Communication strategies in an international school citizen science program investigating marine litter
Authors: Thiel Martin , Baeza Álvarez Jostein , Diaz Manuel , de Veer Diamela , Dittmann Sinja , Guevara-Torrejón Valeska , Ahumada Geraldine Holtmann , Honorato-Zimmer Daniela , Kiessling Tim , Leyton Muñoz Ailin , López-Xalín Ninoshka , Nuñez Paloma , Sepúlveda José Miguel , Vásquez Nelson
Published: November 2023

Communication is an essential element of science, and while it is important in all scientific endeavors, it gains substantial strategic relevance in citizen science projects. For a school citizen science program to be successful, an adequate communication strategy needs to achieve a balance between learning objectives and the generation of scientific knowledge. In this community case study, we report on the communication strategies of an international network, namely, the citizen science program Científicos de la Basura (Litter Scientists), which collaborates with schoolteachers and schoolchildren to investigate anthropogenic litter on marine beaches and in rivers. The program has been active in Chile since 2007, and as of 2018, it had expanded to the 11 countries from the central and southern East Pacific. More than 40 teachers and collaborators from these countries work in this network making an effort to connect the research activities with the learning objectives of the school curriculum. The communication between the coordination team and the teachers includes three main elements (1 - design and planning; 2 - training and research; 3 - evaluation and sharing), with the following activities: (1a) regular internal communication within the coordination team to design, motivate and supervise adequate research projects, (1b) communication with teachers to design appropriate learning materials (co-creation) and get their feedback on the planned research activities, (2a) sharing the final research plan and transfer methodological skills through regular training of the teachers, (2b) responding to methodological questions by the teachers about the sampling, and coordinate data collection and validation, (3a) guiding teachers and schoolchildren in the evaluation and interpretation of their research results, and (3b) encouraging teachers and schoolchildren to communicate their scientific findings to the wider community. Intense internal communication and regular exchange with teachers guarantees successful learning and rigorous scientific information. The main challenges for the program are team capacity, socio-economic stability, internet access, and teachers’ workloads. Recommendations to achieve successful communication and good science are efficient team communication skills, customized contacts, collaborative work, guidance of field work, feedback from participants, and promoting the sense of community.
The impact of ESG ratings under market soft regulation on corporate green innovation: an empirical study from informal environmental governance
Authors: Chen Cheng , Fan Min , Fan Yaojun
Published: November 2023

Enhancing corporate green innovation is a crucial pathway towards achieving a green economic transformation. Diverging from the literature focusing on government environmental regulations and hard regulatory approaches, this study investigates how market soft regulation intervenes in corporate green innovation. From the perspective of informal environmental governance, this paper employs a multi-period difference-in-differences empirical model to examine the impact of ESG ratings on corporate green innovation. The findings reveal that ESG ratings have a positive influence on corporate green innovation. Specifically, ESG ratings encourage firms to increase the number of green patents application and authorization, thereby stimulating investment and innovation activities in the realm of green innovation. These conclusions remain robust after undergoing various statistical tests. In the analysis of moderating effects, this paper discovers a negative inhibitory effect of financing constraints on the relationship between ESG ratings and corporate green innovation. Additionally, the study finds that ESG ratings exhibit a more pronounced promotion effect on green innovation among high-pollution and high-quality information disclosure firms. The research emphasizes the importance for enterprises to undertake proactive strategic adjustments and provides insights for optimizing existing green development policies.
A content analysis of media coverage on road safety and road traffic crashes in Colombia
Authors: Saporito Kristi , Rothenstein-Henry Rachel , Zeynalova Elizaveta , Negi Nalin Singh , Mullin Sandra , Morozova Irina , Murukutla Nandita
Published: November 2023

Introduction: In Colombia, road traffic crashes are the eighth leading cause of death. In 2017, as part of the Bloomberg Philanthropies Initiative for Global Road Safety (BIGRS), Vital Strategies supported government-led journalist trainings in Colombia to shift media discourse of road safety as a public health and development issue with known risk factors and achievable solutions, to ultimately catalyze public and policymaker concern and action. This study evaluates the effects these trainings had on road safety reporting.

Methods: Articles about BIGRS road safety work published between 1 May 2017 and Aug. 30, 2021 were collected from a database maintained by communication officers. The sample included 870 articles, which were systematically analyzed for year-wise frequency by independent coders. Inter-reliability (Cohen’s Kapp K > 0.94) was established using a codebook developed to identify examples of best practices shared during trainings.

Results: From 2017 to 2021, there was a 27% increase in articles that situated road traffic collisions (RTCs) as due to systemic issues (thematic framing) rather than isolated events (episodic framing). Almost all observed articles used at least one WHO-recommended story angle (96%) and key element (95%). Reporting angles focused on the human story were largely underutilized (2%–5%). Government representatives (81%), mostly from the Secretary of Mobility (67%), were the most cited sources and road safety advocates were the least (3%). Use of terms “crash” and “collision” increased across the study period (crash: 47% in 2017 to 59% in 2021; collision: 0.4% in 2019 to 5% in 2020). However, RTCs continued to be widely called “accidents” (46%). More than half of articles referenced either “victims” or “vulnerable road users” (55%); use of “person” to refer to victims/vulnerable road users increased from 33% in 2017 to 56% in 2020.

Conclusion: Over the course of the BIGRS journalist training program, reporting in Colombia increasingly used best practices to frame road safety as a public health issue. This highlights how media engagement is important to comprehensive road safety strategies and should be more widely adopted. Future training efforts should focus on finding the human story, and on changing overreliance on terms like “accident” that make RTCs seem inevitable.
Unlocking the potential of RNA-based therapeutics in the lung: current status and future directions
Authors: Man H. S. Jeffrey , Moosa Vaneeza A. , Singh Anand , Wu Licun , Granton John T. , Juvet Stephen C. , Hoang Chuong D. , de Perrot Marc
Published: November 2023

Awareness of RNA-based therapies has increased after the widespread adoption of mRNA vaccines against SARS-CoV-2 during the COVID-19 pandemic. These mRNA vaccines had a significant impact on reducing lung disease and mortality. They highlighted the potential for rapid development of RNA-based therapies and advances in nanoparticle delivery systems. Along with the rapid advancement in RNA biology, including the description of noncoding RNAs as major products of the genome, this success presents an opportunity to highlight the potential of RNA as a therapeutic modality. Here, we review the expanding compendium of RNA-based therapies, their mechanisms of action and examples of application in the lung. The airways provide a convenient conduit for drug delivery to the lungs with decreased systemic exposure. This review will also describe other delivery methods, including local delivery to the pleura and delivery vehicles that can target the lung after systemic administration, each providing access options that are advantageous for a specific application. We present clinical trials of RNA-based therapy in lung disease and potential areas for future directions. This review aims to provide an overview that will bring together researchers and clinicians to advance this burgeoning field.
Causal associations of sleep traits with cancer incidence and mortality
Authors: Tian Shanshan , Huangfu Longtao , Bao Yanping , Ai Sizhi , Chang Suhua , Wang Qianwen , Zhu Ximei , Yan Wei , Shi Jie , Shi Le , Deng Jiahui , Lu Lin
Published: November 2023

To explore the correlation and causality between multidimensional sleep traits and pan-cancer incidence and mortality among patients with cancer. The multivariable Cox regression, linear and nonlinear Mendelian randomization (MR), and survival curve analyses were conducted to assess the impacts of chronotype, sleep duration, and insomnia symptoms on pan-cancer risk (N = 326,417 from United Kingdom Biobank) and mortality (N = 23,956 from United Kingdom Biobank). In the Cox regression, we observed a linear and J-shaped association of sleep duration with pan-cancer incidence and mortality among cancer patients respectively. In addition, there was a positive association of insomnia with pan-cancer incidence (HR, 1.03, 95% CI: 1.00–1.06, p = 0.035), all-cause mortality (HR, 1.17, 95% CI: 1.06–1.30, p = 0.002) and cancer mortality among cancer patients (HR, 1.25, 95% CI: 1.11–1.41, p < 0.001). In the linear MR, there was supporting evidence of positive associations between long sleep duration and pan-cancer incidence (OR, 1.41, 95% CI: 1.08–1.84, p = 0.012), and there was a positive association between long sleep duration and all-cause mortality in cancer patients (OR, 5.56, 95% CI: 3.15–9.82, p = 3.42E-09). Meanwhile, a strong association between insomnia and all-cause mortality in cancer patients (OR, 1.41, 95% CI: 1.27–1.56, p = 4.96E-11) was observed in the linear MR. These results suggest that long sleep duration and insomnia play important roles in pan-cancer risk and mortality among cancer patients. In addition to short sleep duration and insomnia, our findings highlight the effect of long sleep duration in cancer prevention and prognosis.
Genetic divergence in common bean genotypes from the IRAD gene bank: morpho-agronomic characteristics, fungal and bacterial disease resistance, and opportunities for genetic improvement
Authors: Kouam Eric Bertrand , Djeugap-Fovo Joseph , Meka-Sindje Solange , Afsah Nadia Mokia Mbinkar , Meyia Arielle , Babagnack Blaise Franky , Nouteka Niky K. J. , Galani-Yamdeu Joseph Hubert
Published: November 2023

For successful plant breeding in any crop species, the importance of diversity in the available germplasm population is known and established. Thirty-two common bean (Phaseolus vulgaris) genotypes from the IRAD gene bank in Cameroon were evaluated for divergence in terms of their morpho-agronomic traits, fungal disease resistance, and bacterial disease resistance to assess the opportunity for genetic improvement of the crop. The trait associations were estimated using correlation coefficients and genotypes were classified into groups using cluster and principal component analyses. Seven qualitative and 16 quantitative traits comprising growth, phenological, yield, and disease variables were evaluated in this study. The qualitative markers revealed the degree of polymorphism among the 32 common bean genotypes. The number of phenotypic classes per character (Na) ranged from 2 to 18, with an average of 5.14. The expected gene diversity (He) ranged from 0.37 to 0.93 (mean = 0.56). The number of effective phenotypic classes (Ne) ranged from 1.82 to 14.22, with a mean of 3.85. An extensive range of variation was evident for the majority of traits, highlighting their utility for characterizing common bean germplasm. Many qualitative traits, including seed coat color, seed shape, and seed size, and also some quantitative traits of economic importance including seed yield, were found to be highly variable within the collection, with the MAC55 genotype displaying the highest yield (32.65 g per plant). Four genotypes, namely MAC55, BOA-5-1M6, FEB 192, and Banguem showed resistance to the two main common bean diseases, angular leaf spot and common blight. We detected highly significant correlations among several traits related to yield. A high broad-sense heritability was found for most of the quantitative traits. We carried out two-dimensional principal component analysis and used hierarchical clustering to group the analyzed germplasm according to their phenotypic similitudes. The evidence of agro-morphological diversity in the present collection and the identification of discriminant characters between the available germplasm through the use of PCA analysis have significant implications for establishing breeding schemes in common bean.
Reviewing the reviews: the Global Compacts' added value in access to asylum procedures and immigration detention
Authors: Atak Idil , Grundler Maja , Endres de Oliveira Pauline , Bast Jurgen , Guild Elspeth , Maple Nicholas , Vanyoro Kudakwashe , Wessels Janna , Zyfi Jona
Published: November 2023

The Global Compact for Migration and the Global Compact on Refugees are based on binding international law instruments whose provisions they complement with “best practice” standards related to the treatment of refugees and other migrants. Although the Compacts are non-binding, they provide for review mechanisms to promote compliance with Compact standards. Such oversight is important to achieve progress in implementing the Compacts' commitments. Yet, the current top-down and State-led review process does not offer an efficient platform for identifying cases of non-adherence to Compact standards. This article uses a case study approach to highlight instances of non-compliance with Compact standards in Canada, South Africa, and the European Union. We use a functionalist method of comparison to analyze State practice in these three regions in relation to (i) use of immigration detention and (ii) access to the asylum procedure, with access to healthcare as a cross-cutting issue. The article discusses how the Compacts' review mechanisms could be improved and their added value in terms of their impact on domestic migration policies. It argues that both Compact review and implementation can be improved through increased civil society participation.
Rat cytomegalovirus efficiently replicates in dendritic cells and induces changes in their transcriptional profile
Authors: Madela-Mönchinger Julia Cecilia , Wolf Silver Anthony , Wyler Emanuel , Bauer Agnieszka , Mischke Marius , Möller Lars , Juranić Lisnić Vanda , Landthaler Markus , Malyshkina Anna , Voigt Sebastian
Published: November 2023

Dendritic cells (DC) play a crucial role in generating and maintaining antiviral immunity. While DC are implicated in the antiviral defense by inducing T cell responses, they can also become infected by Cytomegalovirus (CMV). CMV is not only highly species-specific but also specialized in evading immune protection, and this specialization is in part due to characteristic genes encoded by a given virus. Here, we investigated whether rat CMV can infect XCR1+ DC and if infection of DC alters expression of cell surface markers and migration behavior. We demonstrate that wild-type RCMV and a mutant virus lacking the γ-chemokine ligand xcl1 (Δvxcl1 RCMV) infect splenic rat DC ex vivo and identify viral assembly compartments. Replication-competent RCMV reduced XCR1 and MHCII surface expression. Further, gene expression of infected DC was analyzed by bulk RNA-sequencing (RNA-Seq). RCMV infection reverted a state of DC activation that was induced by DC cultivation. On the functional level, we observed impaired chemotactic activity of infected XCR1+ DC compared to mock-treated cells. We therefore speculate that as a result of RCMV infection, DC exhibit diminished XCR1 expression and are thereby blocked from the lymphocyte crosstalk.
Macrophage IL-1β-positive microvesicles exhibit thrombo-inflammatory properties and are detectable in patients with active juvenile idiopathic arthritis
Authors: Cambon Audrey , Rebelle Charlotte , Bachelier Richard , Arnaud Laurent , Robert Stéphane , Lagarde Marie , Muller Romain , Tellier Edwige , Kara Yéter , Leroyer Aurélie , Farnarier Catherine , Vallier Loris , Chareyre Corinne , Retornaz Karine , Jurquet Anne-Laure , Tran Tu-Anh , Lacroix Romaric , Dignat-George Françoise , Kaplanski Gilles
Published: November 2023

Objective

IL-1β is a leaderless cytokine with poorly known secretory mechanisms that is barely detectable in serum of patients, including those with an IL-1β-mediated disease such as systemic juvenile idiopathic arthritis (sJIA). Leukocyte microvesicles (MVs) may be a mechanism of IL-1β secretion. The first objective of our study was to characterize IL-1β-positive MVs obtained from macrophage cell culture supernatants and to investigate their biological functions in vitro and in vivo. The second objective was to detect circulating IL-1β-positive MVs in JIA patients.

Methods

MVs were purified by serial centrifugations from PBMCs, or THP-1 differentiated into macrophages, then stimulated with LPS ± ATP. MV content was analyzed for the presence of IL-1β, NLRP3 inflammasome, caspase-1, P2X7 receptor, and tissue factor (TF) using ELISA, Western blot, or flow cytometry. MV biological properties were studied in vitro by measuring VCAM-1, ICAM-1, and E-selectin expression after HUVEC co-culture and factor-Xa generation test was realized. In vivo, MVs’ ability to recruit leukocytes in a murine model of peritonitis was evaluated. Plasmatic IL-1β-positive MVs were studied ex vivo in 10 active JIA patients using flow cytometry.

Results

THP-1-derived macrophages stimulated with LPS and ATP released MVs, which contained NLRP3, caspase-1, and the 33-kDa precursor and 17-kDa mature forms of IL-1β and bioactive TF. IL-1β-positive MVs expressed P2X7 receptor and released soluble IL-1β in response to ATP stimulation in vitro. In mice, MVs induced a leukocyte peritoneal infiltrate, which was reduced by treatment with the IL-1 receptor antagonist. Finally, IL-1β-positive MVs were detectable in plasma from 10 active JIA patients.

Conclusion

MVs shed from activated macrophages contain IL-1β, NLRP3 inflammasome components, and TF, and constitute thrombo-inflammatory vectors that can be detected in the plasma from active JIA patients.
Antibodies to S2 domain of SARS-CoV-2 spike protein in Moderna mRNA vaccinated subjects sustain antibody-dependent NK cell-mediated cell cytotoxicity against Omicron BA.1
Authors: Balinsky Corey A. , Jiang Le , Jani Vihasi , Cheng Ying , Zhang Zhiwen , Belinskaya Tatyana , Qiu Qi , Long Tran Khanh , Schilling Megan A. , Jenkins Sarah A. , Corson Karen S. , Martin Nicholas J. , Letizia Andrew G. , Hontz Robert D. , Sun Peifang
Published: November 2023

Vaccination with the primary two-dose series of SARS-CoV-2 mRNA protects against infection with the ancestral strain, and limits the presentation of severe disease after re-infection by multiple variants of concern (VOC), including Omicron, despite the lack of a strong neutralizing response to these variants. We compared antibody responses in serum samples collected from mRNA-1273 (Moderna) vaccinated subjects to identify mechanisms of immune escape and cross-protection. Using pseudovirus constructs containing domain-specific amino acid changes representative of Omicron BA.1, combined with domain competition and RBD-antibody depletion, we showed that RBD antibodies were primarily responsible for virus neutralization and variant escape. Antibodies to NTD played a less significant role in antibody neutralization but acted along with RBD to enhance neutralization. S2 of Omicron BA.1 had no impact on neutralization escape, suggesting it is a less critical domain for antibody neutralization; however, it was as capable as S1 at eliciting IgG3 responses and NK-cell mediated, antibody-dependent cell cytotoxicity (ADCC). Antibody neutralization and ADCC activities to RBD, NTD, and S1 were all prone to BA.1 escape. In contrast, ADCC activities to S2 resisted BA.1 escape. In conclusion, S2 antibodies showed potent ADCC function and resisted Omicron BA.1 escape, suggesting that S2 contributes to cross-protection against Omicron BA.1. In line with its conserved nature, S2 may hold promise as a vaccine target against future variants of SARS-CoV-2.
Environmental bisphenol A exposure triggers trained immunity-related pathways in monocytes
Authors: Dallio Marcello , Ventriglia Lorenzo , Romeo Mario , Scognamiglio Flavia , Diano Nadia , Moggio Martina , Cipullo Marina , Coppola Annachiara , Ziogas Athanasios , Netea Mihai G. , Federico Alessandro
Published: November 2023

Introduction

Trained Immunity represents a novel revolutionary concept of the immunological response involving innate immune cells. Bisphenol A is a well-known endocrine disrupter, widely disseminated worldwide and accumulated in the human body. Due to the increased interest regarding the effects of plastic-derived compounds on the immune system, our purpose was to explore whether BPA was able to induce trained immunity in human primary monocytes in vitro using low environmental concentrations.

Materials and methods

We extracted BPA from the serum of 10 healthy individuals through a liquid-liquid extraction followed by a solid phase extraction and measured the concentration using an HPLC system coupled to a triple quadrupole mass spectrometer. In parallel, monocytes were isolated from whole blood and acutely stimulated or trained with BPA at three different concentrations (1 nM, 10 nM, 20 nM). Pro- and anti-inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-10) production were assessed after 24 hours of acute stimulation and after Lipopolysaccharide (LPS) rechallenge. A comprehensive overview of the metabolic changes after BPA acute stimulation and trained immunity induction was assessed through extracellular lactate measurements, Seahorse XFb metabolic flux analysis and ROS production.

Results

Monocytes primed with BPA showed increased pro- and anti-inflammatory cytokine responses upon restimulation, sustained by the modulation of the immunometabolic circuits. Moreover, we proved the non-toxic effect of BPA at each experimental concentration by performing an MTT assay. Additionally, correlation analysis were performed between pro- and anti-inflammatory cytokines production after LPS acute stimulation or BPA-mediated trained immunity and BPA serum concentrations showing a significant association between TNF-α and BPA circulating levels.

Discussion

Overall, this study pointed out for the first time the immunological effects of an environmental chemical and plastic-derived compound in the induction of trained immunity in a healthy cohort.
The relationship between atrial fibrillation and NLRP3 inflammasome: a gut microbiota perspective
Authors: Xing Yaxuan , Yan Longmei , Li Xiaoya , Xu Zhijie , Wu Xianyu , Gao Huirong , Chen Yiduo , Ma Xiaojuan , Liu Jiangang , Zhang Jingchun
Published: November 2023

Atrial fibrillation (AF) is a common clinical arrhythmia whose pathogenesis has not been fully elucidated, and the inflammatory response plays an important role in the development of AF. The inflammasome is an important component of innate immunity and is involved in a variety of pathophysiologic processes. The NLRP3 inflammasome is by far the best studied and validated inflammasome that recognizes multiple pathogens through pattern recognition receptors of innate immunity and mediates inflammatory responses through activation of Caspase-1. Several studies have shown that NLRP3 inflammasome activation contributes to the onset and development of AF. Ecological dysregulation of the gut microbiota has been associated with the development of AF, and some evidence suggests that gut microbiota components, functional byproducts, or metabolites may induce or exacerbate the development of AF by directly or indirectly modulating the NLRP3 inflammasome. In this review, we report on the interconnection of NLRP3 inflammasomes and gut microbiota and whether this association is related to the onset and persistence of AF. We discuss the potential value of pharmacological and dietary induction in the management of AF in the context of the association between the NLRP3 inflammasome and gut microbiota. It is hoped that this review will lead to new therapeutic targets for the future management of AF.
Anti-PD1 does not improve pyroptosis induced by γδ T cells but promotes tumor regression in a pleural mesothelioma mouse model
Authors: Lui Ka Sin , Ye Zuodong , Chan Hoi Ching , Tanaka Yoshimasa , Cheung Allen Ka Loon
Published: November 2023

Introduction

Mesothelioma is an aggressive tumor in the pleural cavity that is difficult to treat. Diagnosis is usually late with minimal treatment options available for the patients and with unfavorable outcomes. However, recent advances in immunotherapy using γδ T cells may have potential against mesothelioma, given its ample tumoricidal and tumor-migratory properties could allow its infiltration to the widespread tumor mass. Thus, we hypothesize that Vδ2 T cells can perform cytotoxic activities against mesothelioma especially when combined with immune checkpoint blocker against PD-1.

Methods

Human Vδ2 T cells were expanded from peripheral blood mononuclear cells using Tetrakis‐pivaloyloxymethyl 2‐(thiazole‐2‐ylamino) ethylidene‐1,1‐bisphosphonate (PTA) plus IL-2 for 13 days, before used to test for cytotoxicity against mesothelioma cell lines. Mesothelioma-bearing mice was established by Intrapleural administration of mesothelioma cell lines to test for the efficacy of Vδ2 T cells plus anti-PD-1 antibody combination treatment. Pyroptosis was evaluated by cell morphology, western blot analysis, and ELISA experiments. Flow cytometry was used to examine expression of BTN2A1, BTN3A1, PD-L1, PD-L2 on mesothelioma cell lines. Immunofluorescence staining was performed to detect Vδ2 T cells post adoptive transfer and characteristics of pyroptosis in ex vivo mesothelioma tissue sections.

Results

Indeed, our data demonstrated that Vδ2 T cells killing mesothelioma can be enhanced by anti-PD-1 antibody in vitro, especially for high PD-1 expressing cells, and in vivo in the intrapleural mesothelioma mice model established by us. Adoptive transfer of Vδ2 T cells into these mice leads to tumor regression by 30-40% compared to control. Immunofluorescence of the tumor section confirmed infiltration of Vδ2 T cells into the tumor, especially to cells with BTN2A1 expression (a Vδ2 T cell activating molecule) despite PD-L1 co-localization. Interestingly, these cells co-expressed cleaved gasdermin D, suggesting that pyroptosis was induced by Vδ2 T cells. This was verified by Vδ2 T/mesothelioma co-culture experiments demonstrating membrane ballooning morphology, increased cleaved caspase-3 and gasdermin E, and upregulated IL-1β and IL-18.

Discussion

Vδ2 T cells plus anti-PD1 exhibited cytotoxicity against mesothelioma in vivo. However, we found no advantage for anti-PD-1 against PD-1 high expressing Vδ2 T cells in promoting pyroptosis. Taken together, our work demonstrated that Vδ2 T cells combined with anti-PD-1 antibody can be developed as a potential combination immunotherapy for mesothelioma.
Escherichia coli adhesion protein FimH exacerbates colitis via CD11b+CD103- dendritic cell activation
Authors: Zhang Wei , An Eun-Koung , Kim So-Jung , Park Hae-Bin , Lee Peter C. W. , Jin Jun-O
Published: November 2023

Introduction

Immune stimulators are used to improve vaccine efficiency; however, they are accompanied by various side effects. In previous studies, we reported that the Escherichia coli adhesion protein, FimH, induces immune activity; however, we did not examine any side effects in colon inflammation.

Methods

FimH was administered orally or intraperitoneally (i.p.) to mice with dextran sulfate sodium (DSS)-induced colitis, and changes in symptoms were observed. Immune cells infiltrated into the colon after the induction of colon inflammation were analyzed using a flow cytometer. Changes in Th1 and Th17 cells that induce colitis were analyzed. Further, mesenteric lymph node (mLN) dendritic cells (DCs) activated by FimH were identified and isolated to examine their ability to induce T-cell immunity.

Results

FimH oral and i.p. administration in C57BL/6 mice did not induce inflammation in the colon; however, DSS-induced colitis was exacerbated by oral and i.p. FimH administration. FimH treatment increased immune cell infiltration in the colon compared to that in DSS colitis. Th1 and Th17 cells, which are directly related to colitis, were increased in the colon by FimH; however, FimH did not directly affect the differentiation of these T cells. FimH upregulated the CD11b+CD103- DC activity in the mLNs, which produced the signature cytokines required for Th1 and Th17. In addition, isolated CD11b+CD103- DCs, after stimulation with FimH, directly induced Th1 and Th17 differentiation in a co-culture of CD4 T cells.

Conclusion

This study demonstrated the side effects of FimH and indicated that the use of FimH can aggravate the disease in patients with colitis.
HLA diversity in ethnic populations can affect detection of donor-specific antibodies by single antigen beads
Authors: Quon Justin C. , Kaneta Kelli , Fotiadis Nicholas , Menteer Jondavid , Lestz Rachel M. , Weisert Molly , Baxter-Lowe Lee Ann
Published: November 2023

Introduction

In solid-organ transplantation, human leukocyte antigen (HLA) donor-specific antibodies (DSA) are strongly associated with graft rejection, graft loss, and patient death. The predominant tests used for detecting HLA DSA before and after solid-organ transplantation are HLA single antigen bead (SAB) assays. However, SAB assays may not detect antibodies directed against HLA epitopes that are not represented in the SAB. The prevalence and potential impact of unrepresented HLA epitopes are expected to vary by ethnicity, but have not been thoroughly investigated. To address this knowledge gap, HLA allele frequencies from seven ethnic populations were compared with HLA proteins present in SAB products from two manufacturers to determine unrepresented HLA proteins.

Materials

Allele frequencies were obtained from the Common, Intermediate, and Well Documented HLA catalog v3.0, and frequencies of unrepresented HLA types were calculated. Next-generation sequencing was used to determine HLA types of 60 deceased solid-organ donors, and results were used to determine if their HLA-A, -B, -C, and -DRB1 proteins were not present in SAB reagents from two vendors. Unrepresented HLA proteins were compared with the most similar protein in SAB assays from either vendor and then visualized using modeling software to assess potential HLA epitopes.

Results

For the seven ethnic populations, 0.5% to 11.8% of each population had HLA proteins not included in SAB assays from one vendor. Non-European populations had greater numbers of unrepresented alleles. Among the deceased donors, 26.7% (16/60) had at least one unrepresented HLA-A, -B, -C, or -DRB1 protein. Structural modeling demonstrated that a subset of these had potential HLA epitopes that are solvent accessible amino acid mismatches and are likely to be accessible to B cell receptors.

Discussion

In conclusion, SAB assays cannot completely rule out the presence of HLA DSA. HLA epitopes not represented in those assays vary by ethnicity and should not be overlooked, especially in non-European populations. Allele-level HLA typing can help determine the potential for HLA antibodies that could evade detection.
Impact of rising seawater temperature on a phagocytic cell population during V. parahaemolyticus infection in the sea anemone E. pallida
Authors: Billaud Mélanie , Larbret Frédéric , Czerucka Dorota
Published: November 2023

Climate change is increasing ocean temperatures and consequently impacts marine life (e.g., bacterial communities). In this context, studying host–pathogen interactions in marine organisms is becoming increasingly important, not only for ecological conservation, but also to reduce economic loss due to mass mortalities in cultured species. In this study, we used Exaiptasia pallida (E. pallida), an anemone, as an emerging marine model to better understand the effect of rising temperatures on the infection induced by the pathogenic marine bacterium Vibrio parahaemolyticus. The effect of temperature on E. pallida was examined at 6, 24, or 30 h after bath inoculation with 108 CFU of V. parahaemolyticus expressing GFP (Vp-GFP) at 27°C (husbandry temperature) or 31°C (heat stress). Morphological observations of E. pallida and their Hsps expression demonstrated heat stress induced increasing damage to anemones. The kinetics of the infections revealed that Vp-GFP were localized on the surface of the ectoderm and in the mucus during the first hours of infection and in the mesenterial filaments thereafter. To better identify the E. pallida cells targeted by Vp-GFP infection, we used spectral flow cytometry. E. pallida cell types were identified based on their autofluorescent properties. corresponding to different cell types (algae and cnidocytes). We identified an AF10 population whose autofluorescent spectrum was identical to that of human monocytes/macrophage, suggesting that this spectral print could be the hallmark of phagocytic cells called “amebocytes’’. AF10 autofluorescent cells had a high capacity to phagocytize Vp-GFP, suggesting their possible role in fighting infection. This was confirmed by microscopy using sorted AF10 and GFP-positive cells (AF10+/GFP+). The number of AF10+/GFP+ cells were reduced at 31°C, demonstrating that increased temperature not only damages tissue but also affects the immune response of E. pallida. In conclusion, our study provides a springboard for more comprehensive studies of immune defense in marine organisms and paves the way for future studies of the dynamics, activation patterns, and functional responses of immune cells when encountering pathogens.
Herpes zoster in lupus nephritis: experience on 292 patients followed up for 15 years
Authors: Reggiani Francesco , Cardi Silvia , Tumminello Fabio , Calatroni Marta , Locatelli Laura , Gerosa Maria , Del Papa Nicoletta , Moroni Gabriella
Published: November 2023

Objectives

To evaluate the prevalence, incidence, and predictors of herpes zoster (HZ) development in lupus nephritis (LN).

Methods

This retrospective study included 292 LN patients to determine HZ incidence during the last decades and its correlation with LN activity. LN patients with HZ were matched with LN patients without HZ in a 1:2 ratio based on sex, age, year of LN diagnosis, and LN histological class at kidney biopsy to assess HZ risk factors. Statistical tests included t-test, U-test, and Fisher’s test. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors.

Results

HZ occurred after LN diagnosis in 66 patients (prevalence 22.6%) with an average of 8.7 years (range 0.2–28.4 years). Although with the potential limitations of the retrospective nature and the extensive duration of the study, the incidence of HZ was 15.6/1,000 person-years, increasing from 6.9 before 1980 to 16.0 in the 1990s and 43.9 after 2010. HZ onset was unrelated to LN activity. LN was active in 43% of cases and quiescent in the other 57% of cases at HZ diagnosis. The percentage of patients who developed lupus flares during the year after HZ (18.9%) was not different from that which occurred during the year before HZ (17.2%, p = 0.804). After excluding confounding factors through matching, the univariate analysis suggested that cyclosporin during induction therapy (p = 0.011) and higher cumulative doses of glucocorticoids (GCs; >50 g, p = 0.004), cyclophosphamide (CYC; >5 g, p = 0.001), and mycophenolate mofetil (MMF > 1,000 g, p = 0.007) predisposed patients to HZ. Univariate and multivariate analyses revealed a protective role of azathioprine (p = 0.008) and methylprednisolone pulses (p = 0.010) during induction therapy.

Conclusions

HZ occurs unpredictably throughout the course of LN, underscoring the importance of continuous monitoring for these patients. In addition, the incidence of HZ seems to have increased in recent decades. Induction therapy with azathioprine and methylprednisolone pulses appears to provide protection, while higher cumulative doses of GCs, CYC, and MMF increase susceptibility.
FANCI serve as a prognostic biomarker correlated with immune infiltrates in skin cutaneous melanoma
Authors: Cai Zhenguo , Duan Yanjuan , Li Wen , Liu Zhuohang , Gong Zijun , Hong Sheng , He Xu , Xuanyuan Xinyang , Chen Youdong , Bi Xinling , Wang Wuqing
Published: November 2023

Background

As a member of tumor, Skin cutaneous melanoma (SKCM) poses a serious threat to people’s health because of its strong malignancy. Unfortunately, effective treatment methods for SKCM remain lacking. FANCI plays a vital role in the occurrence and metastasis of various tumor types. However, its regulatory role in SKCM is unclear. The purpose of this study was to explore the association of FANCI with SKCM.

Methods

This study investigated the expression of FANCI in GSE46517, GSE15605, and GSE114445 from the Gene Expression Omnibus database and The Cancer Genome Atlas (TCGA)-SKCM datasets using the package “limma” or “DESeq2” in R environment and also investigated the prognostic significance of FANCI by utilizing the GEPIA database. Additionally, our research made use of real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) staining to verify FANCI expression between SKCM and normal tissues and developed the knockdown of FANCI in A375 and A875 cells to further analyze the function of FANCI. Finally, this study analyzed the correlation of FANCI and tumor-infiltrating immune cells by CIBERSORT, ESTIMATE, and ssGSEA algorithms.

Results

The FANCI level was increasing in SKCM tissues from GSE46517, GSE15605, GSE114445, and TCGA-SKCM. However, high FANCI expression correlated with poor overall survival. The RT-qPCR and IHC confirmed the accuracy of bioinformatics. Knocking down FANCI suppresses A375 and A875 cell proliferation, migration, and invasion. FANCI could be involved in the immunological milieu of SKCM by regulating immune responses and infiltrating numerous immune cells, particularly neutrophils, CD8+ T cells, and B cells. Furthermore, patients with SKCM who have a high FANCI expression level are reported to exhibit immunosuppression, whereas those with a low FANCI expression level are more likely to experience positive outcomes from immunotherapy.

Conclusions

The increased FANCI expression in SKCM can be a prognostic biomarker. Knockdown FANCI can reduce the occurrence and progression of SKCM. The FANCI expression provides a foundation for predicting the immune status and treatment of SKCM.
Single-cell sequencing analysis related to sphingolipid metabolism guides immunotherapy and prognosis of skin cutaneous melanoma
Authors: Ding Yantao , Zhao Zhijie , Cai Huabao , Zhou Yi , Chen He , Bai Yun , Liu Zhenran , Liu Shengxiu , Zhou Wenming
Published: November 2023

Background

We explore sphingolipid-related genes (SRGs) in skin melanoma (SKCM) to develop a prognostic indicator for patient outcomes. Dysregulated lipid metabolism is linked to aggressive behavior in various cancers, including SKCM. However, the exact role and mechanism of sphingolipid metabolism in melanoma remain partially understood.

Methods

We integrated scRNA-seq data from melanoma patients sourced from the GEO database. Through the utilization of the Seurat R package, we successfully identified distinct gene clusters associated with patient survival in the scRNA-seq data. Key prognostic genes were identified through single-factor Cox analysis and used to develop a prognostic model using LASSO and stepwise regression algorithms. Additionally, we evaluated the predictive potential of these genes within the immune microenvironment and their relevance to immunotherapy. Finally, we validated the functional significance of the high-risk gene IRX3 through in vitro experiments.

Results

Analysis of scRNA-seq data identified distinct expression patterns of 4 specific genes (SRGs) in diverse cell subpopulations. Re-clustering cells based on increased SRG expression revealed 7 subgroups with significant prognostic implications. Using marker genes, lasso, and Cox regression, we selected 11 genes to construct a risk signature. This signature demonstrated a strong correlation with immune cell infiltration and stromal scores, highlighting its relevance in the tumor microenvironment. Functional studies involving IRX3 knockdown in A375 and WM-115 cells showed significant reductions in cell viability, proliferation, and invasiveness.

Conclusion

SRG-based risk signature holds promise for precise melanoma prognosis. An in-depth exploration of SRG characteristics offers insights into immunotherapy response. Therapeutic targeting of the IRX3 gene may benefit melanoma patients.