bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconsidering reproductive patterns in a model dissociated species, the red-sided garter snake: Sex-specific and seasonal changes in gonadal steroidogenic gene expression
Authors: Lincoln Julianna M. , Barlowe Megan L. , Rucker Holly R. , Parker M. Rockwell
Published: March 2023

Sex steroid hormones are powerful regulators of reproductive behavior and physiology in vertebrates, and steroidogenesis has distinct sex- and season-specific patterns ultimately dictated by the expression of key enzymes. Most comparative endocrinology studies, however, focus only on circulating levels of sex steroids to determine their temporal association with life-history events in what are termed associated reproductive patterns. The red-sided garter snake (Thamnophis sirtalis parietalis) is a notable exception; this species exhibits maximal sex behavior decoupled from maximal sex steroid production and gametogenesis in what is termed a dissociated reproductive pattern. And while this is true for male red-sided garter snakes and their production of testosterone, females have maximal estradiol production during peak breeding (spring) but only immediately after mating. Here, we demonstrate that expression of ovarian aromatase (conversion of androgens to estrogens) matches the established seasonal hormone pattern in females. Additionally, steroidogenic gene expression in the ovary is broadly reduced if not suppressed compared to the testis throughout the active year. Bizarrely, male red-sided garter snakes demonstrate an unexplained pattern of steroidogenic gene expression in the testis. StAR (import of cholesterol to steroidogenesis) is maximally expressed in spring, yet Hsd17b3 expression (conversion of androstenedione to testosterone) is highest in summer, with the latter matching the established summer peak in male testosterone. The function of elevated StAR in spring is unknown, but our results suggest a decoupling between maximal StAR expression and testosterone biosynthesis (Hsd17b3 expression). We also purport that the reproductive pattern binary should be reassessed given its lack of fit for many vertebrate species that demonstrate seasonal, mixed patterns of (a)synchrony between circulating sex hormones and reproductive behavior.
Multiscale ecological niche modeling exhibits varying climate change impacts on habitat suitability of Madrean Pine-Oak trees
Authors: Carrell Joshua D. , Phinney April I. , Mueller Kaeli , Bean Brennan
Published: March 2023

Anthropogenic climate change and increasing greenhouse gas emissions are expected to globally impact the biological function, community structure, and spatial distribution of biodiversity. Many existing studies explore the effect of climate change on biodiversity, generally at a single spatial scale. This study explores the potential effects of climate change on the habitat suitability of seven tree species at two distinct spatial scales: the Coronado National Forest (CNF), a local management area, and the Sierra Madre Occidental (SMO), an ecoregional extent. Habitat suitability was determined by extrapolating Ecological Niche Models (ENMs) based on citizen-science tree occurrence records into future climatic conditions using projected 30-year normals for two anthropogenic emissions scenarios through the end of the century. These ENMs, examined at a spatial resolution of 1 km2, are constructed using a mean average ensemble of three commonly used machine learning algorithms. The results show that habitat suitability is expected to decrease for all seven tree species at varying degrees. Results also show that climate-forcing scenario choice appears to be far less important for understanding changes in species habitat suitability than the spatial scale of modeling extent. Additionally, we observed non-linear changes in tree species habitat suitability within the SMO and CNF dependent on forest community type, latitude, and elevational gradient. The paper concludes with a discussion of the necessary steps to verify the estimated alters of these tree species under climate change. Most importantly, provides a framework for characterizing habitat suitability across spatial scales.
Genome editing in rice mediated by miniature size Cas nuclease SpCas12f
Authors: Sukegawa Satoru , Nureki Osamu , Toki Seiichi , Saika Hiroaki
Published: March 2023

Cas9 derived from Streptococcus pyogenes (SpCas9) is used widely in genome editing using the CRISPR-Cas system due to its high activity, but is a relatively large molecule (1,368 amino acid (a.a.) residues). Recently, targeted mutagenesis in human cells and maize using Cas12f derived from Syntrophomonas palmitatica (SpCas12f)—a very small Cas of 497 a.a, which is a more suitable size for virus vectors—was reported. However, there are no reports of genome editing using SpCas12f in crops other than maize. In this study, we applied SpCas12f to genome editing in rice—one of the most important staple crops in the world. An expression vector encoding rice codon-optimized SpCas12f and sgRNA for OsTubulin as a target was introduced into rice calli by Agrobacterium-mediated transformation. Molecular analysis of SpCas12f-transformed calli showed that mutations were introduced successfully into the target region. Detailed analysis by amplicon sequencing revealed estimated mutation frequencies (a ratio of the number of mutated calli to that of SpCas12f-transformed calli) of 28.8% and 55.6% in two targets. Most mutation patterns were deletions, but base substitutions and insertions were also confirmed at low frequency. Moreover, off-target mutations by SpCas12f were not found. Furthermore, mutant plants were regenerated successfully from the mutated calli. It was confirmed that the mutations in the regenerated plants were inherited to the next-generation. In the previous report in maize, mutations were introduced by treatment with heat shock at 45°C for 4 h per day for 3 days; no mutations were introduced under normal growth conditions at 28°C. Surprisingly, however, mutations can be introduced without heat-shock treatment in rice. This might be due to the culture conditions, with relatively higher temperature (30°C or higher) and constant light during callus proliferation. Taken together, we demonstrated that SpCas12f can be used to achieve targeted mutagenesis in rice. SpCas12f is thus a useful tool for genome editing in rice and is suitable for virus vector-mediated genome editing due to its very small size.
Engagement marketing for social good: Application to the All of Us Research Program
Authors: Lewis Megan A. , Uhrig Jennifer D. , Adams Elizabeth T. , Brown Jill A. , Sanders Amy ,   the RTI International All of Us Innovator Team
Published: March 2023

Engagement marketing, when applied to increasing the social good, involves making a deliberate effort to engage communities with an organization’s brand that might not have otherwise happened organically. Organizations that typically focus on increasing the social good include non-profits, community organizations, public health departments, and federal, state, and local agencies. Engagement marketing builds relationships, gives a voice to, and fosters collaboration with community members to transform their insights into impactful experiences that motivate and empower them to act to increase the social good. These actions may include making an informed decision, changing a health or prosocial behavior, or joining an effort that promotes or increases social good. In this paper, we translate the commercial engagement marketing approach, typically used, and studied widely to increase profits, to one that uses engagement marketing to increase prosocial outcomes. We propose a new definition of engagement marketing applied to the social good, a multi-level conceptual framework that integrates individual, social, community and macro-level processes and outcomes, and illustrates an example applying this translated model to co-create digital engagement experiences using a human centered design approach for the All of Us Research Program. This model can also guide research and practice related to DNA-based population screening.
Effectiveness of non-invasive chromosomal screening for normal karyotype and chromosomal rearrangements
Authors: Sun Bo-lan , Wang Yong , Sixi-Wen  , Zhou Liang , Zhang Chun-hui , Wu Ze-Xuan , Qiao Jie , Sun Qing-yuan , Yao Ya-xin , Wang Jing , Yi Zi-Yun , Qian Wei-Ping
Published: March 2023

Purpose: To study the accuracy of non-invasive chromosomal screening (NICS) results, in normal chromosomes and chromosomal rearrangement groups and to investigate whether using trophoblast cell biopsy along with NICS, to choose embryos for transfer can improve the clinical outcomes of assisted pregnancy.

Methods: We retrospectively analyzed 101 couples who underwent preimplantation genetic testing at our center from January 2019 to June 2021 and collected 492 blastocysts for trophocyte (TE) biopsy. D3-5 blastocyst culture fluid and blastocyst cavity fluid were collected for the NICS. Amongst them, 278 blastocysts (58 couples) and 214 blastocysts (43 couples) were included in the normal chromosomes and chromosomal rearrangement groups, respectively. Couples undergoing embryo transfer were divided into group A, in which both the NICS and TE biopsy results were euploid (52 embryos), and group B, in which the TE biopsy results were euploid and the NICS results were aneuploid (33 embryos).

Results: In the normal karyotype group, concordance for embryo ploidy was 78.1%, sensitivity was 94.9%, specificity was 51.4%, the positive predictive value (PPV) was 75.7%, and the negative predictive value (NPV) was 86.4%. In the chromosomal rearrangement group, concordance for embryo ploidy was 73.1%, sensitivity was 93.3%, specificity was 53.3%, the PPV was 66.3%, and the NPV was 89%. In euploid TE/euploid NICS group, 52 embryos were transferred; the clinical pregnancy rate was 71.2%, miscarriage rate was 5.4%, and ongoing pregnancy rate was 67.3%. In euploid TE/aneuploid NICS group, 33 embryos were transferred; the clinic pregnancy rate was 54.5%, miscarriage rate was 5.6%, and ongoingpregnancy rate was 51.5%. The clinical pregnancy and ongoing pregnancy rates were higher in the TE and NICS euploid group.

Conclusion: NICS was similarly effective in assessing both normal and abnormal populations. Identification of euploidy and aneuploidy alone may lead to the wastage of embryos due to high false positives. More suitable reporting methods for NICS and countermeasures for a high number of false positives in NICS are needed. In summary, our results suggest that combining biopsy and NICS results could improve the outcomes of assisted pregnancy.
FAIR human neuroscientific data sharing to advance AI driven research and applications: Legal frameworks and missing metadata standards
Authors: Reer Aaron , Wiebe Andreas , Wang Xu , Rieger Jochem W.
Published: March 2023

Modern AI supported research holds many promises for basic and applied science. However, the application of AI methods is often limited because most labs cannot, on their own, acquire large and diverse datasets, which are best for training these methods. Data sharing and open science initiatives promise some relief to the problem, but only if the data are provided in a usable way. The FAIR principles state very general requirements for useful data sharing: they should be findable, accessible, interoperable, and reusable. This article will focus on two challenges to implement the FAIR framework for human neuroscience data. On the one hand, human data can fall under special legal protection. The legal frameworks regulating how and what data can be openly shared differ greatly across countries which can complicate data sharing or even discourage researchers from doing so. Moreover, openly accessible data require standardization of data and metadata organization and annotation in order to become interpretable and useful. This article briefly introduces open neuroscience initiatives that support the implementation of the FAIR principles. It then reviews legal frameworks, their consequences for accessibility of human neuroscientific data and some ethical implications. We hope this comparison of legal jurisdictions helps to elucidate that some alleged obstacles for data sharing only require an adaptation of procedures but help to protect the privacy of our most generous donors to research … our study participants. Finally, it elaborates on the problem of missing standards for metadata annotation and introduces initiatives that aim at developing tools to make neuroscientific data acquisition and analysis pipelines FAIR by design. While the paper focuses on making human neuroscience data useful for data-intensive AI the general considerations hold for other fields where large amounts of openly available human data would be helpful.
A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infections
Authors: Pan Tony , Cao Guoshuai , Tang Erting , Zhao Yu , Penaloza-MacMaster Pablo , Fang Yun , Huang Jun
Published: March 2023

Introduction: Within the inflammatory immune response to viral infection, the distribution and cell type-specific profiles of immune cell populations and the immune-mediated viral clearance pathways vary according to the specific virus. Uncovering the immunological similarities and differences between viral infections is critical to understanding disease progression and developing effective vaccines and therapies. Insight into COVID-19 disease progression has been bolstered by the integration of single-cell (sc)RNA-seq data from COVID-19 patients with data from related viruses to compare immune responses. Expanding this concept, we propose that a high-resolution, systematic comparison between immune cells from SARS-CoV-2 infection and an inflammatory infectious disease with a different pathophysiology will provide a more comprehensive picture of the viral clearance pathways that underscore immunological and clinical differences between infections.

Methods: Using a novel consensus single-cell annotation method, we integrate previously published scRNA-seq data from 111,566 single PBMCs from 7 COVID-19, 10 HIV-1+, and 3 healthy patients into a unified cellular atlas. We compare in detail the phenotypic features and regulatory pathways in the major immune cell clusters.

Results: While immune cells in both COVID-19 and HIV-1+ cohorts show shared inflammation and disrupted mitochondrial function, COVID-19 patients exhibit stronger humoral immunity, broader IFN-I signaling, elevated Rho GTPase and mTOR pathway activity, and downregulated mitophagy.

Discussion: Our results indicate that differential IFN-I signaling regulates the distinct immune responses in the two diseases, revealing insight into fundamental disease biology and potential therapeutic candidates.
Multi-environment analysis enhances genomic prediction accuracy of agronomic traits in sesame
Authors: Sabag Idan , Bi Ye , Peleg Zvi , Morota Gota
Published: March 2023

Introduction: Sesame is an ancient oilseed crop containing many valuable nutritional components. The demand for sesame seeds and their products has recently increased worldwide, making it necessary to enhance the development of high-yielding cultivars. One approach to enhance genetic gain in breeding programs is genomic selection. However, studies on genomic selection and genomic prediction in sesame have yet to be conducted.

Methods: In this study, we performed genomic prediction for agronomic traits using the phenotypes and genotypes of a sesame diversity panel grown under Mediterranean climatic conditions over two growing seasons. We aimed to assess prediction accuracy for nine important agronomic traits in sesame using single- and multi-environment analyses.

Results: In single-environment analysis, genomic best linear unbiased prediction, BayesB, BayesC, and reproducing kernel Hilbert spaces models showed no substantial differences. The average prediction accuracy of the nine traits across these models ranged from 0.39 to 0.79 for both growing seasons. In the multi-environment analysis, the marker-by-environment interaction model, which decomposed the marker effects into components shared across environments and environment-specific deviations, improved the prediction accuracies for all traits by 15%–58% compared to the single-environment model, particularly when borrowing information from other environments was made possible.

Discussion: Our results showed that single-environment analysis produced moderate-to-high genomic prediction accuracy for agronomic traits in sesame. The multi-environment analysis further enhanced this accuracy by exploiting marker-by-environment interaction. We concluded that genomic prediction using multi-environmental trial data could improve efforts for breeding cultivars adapted to the semi-arid Mediterranean climate.
Metabolism-related long non-coding RNA in the stomach cancer associated with 11 AMMLs predictive nomograms for OS in STAD
Authors: Jin Wenjian , Ou Kongbo , Li Yuanyuan , Liu Wensong , Zhao Min
Published: March 2023

Background: The metabolic processes involving amino acids are intimately linked to the onset and progression of cancer. Long non-coding RNAs (LncRNAs) perform an indispensable function in the modulation of metabolic processes as well as the advancement of tumors. Non-etheless, research into the role that amino acid metabolism-related LncRNAs (AMMLs) might play in predicting the prognosis of stomach adenocarcinoma (STAD) has not been done. Therefore, This study sought to design a model for AMMLs to predict STAD-related prognosis and elucidate their immune properties and molecular mechanisms.

Methods: The STAD RNA-seq data in the TCGA-STAD dataset were randomized into the training and validation groups in a 1:1 ratio, and models were constructed and validated respectively. In the molecular signature database, This study screened for genes involved in amino acid metabolism. AMMLs were obtained by Pearson’s correlation analysis, and predictive risk characteristics were established using least absolute shrinkage and selection operator (LASSO) regression, univariate Cox analysis, and multivariate Cox analysis. Subsequently, the immune and molecular profiles of high- and low-risk patients and the benefit of the drug were examined.

Results: Eleven AMMLs (LINC01697, LINC00460, LINC00592, MIR548XHG, LINC02728, RBAKDN, LINCOG, LINC00449, LINC01819, and UBE2R2-AS1) were used to develop a prognostic model. Moreover, high-risk individuals had worse overall survival (OS) than low-risk patients in the validation and comprehensive groups. A high-risk score was associated with cancer metastasis as well as angiogenic pathways and high infiltration of tumor-associated fibroblasts, Treg cells, and M2 macrophages; suppressed immune responses; and a more aggressive phenotype.

Conclusion: This study identified a risk signal associated with 11 AMMLs and established predictive nomograms for OS in STAD. These findings will help us personalize treatment for gastric cancer patients.
Comparative genomics analysis of endangered wild Egyptian Moringa peregrina (Forssk.) Fiori plastome, with implications for the evolution of Brassicales order
Authors: AbdAlla Heba A. M. , Wanga Vincent Okelo , Mkala Elijah Mbandi , Amenu Sara Getachew , Amar Mohamed Hamdy , Chen Lingyun , Wang Qing-Feng
Published: March 2023

Moringa is a mono-genus belonging to the Moringaceae family, which includes 13 species. Among them, Moringa peregrina is plant species native to the Arabian Peninsula, Southern Sinai in Egypt, and the Horn of Africa, and comprehensive studies on its nutritional, industrial, and medicinal values have been performed. Herein, we sequenced and analyzed the initial complete chloroplast genome of Moringa peregrina. Concurrently, we analyzed the new chloroplast genome along with 25 chloroplast genomes related to species representing eight families in the Brassicales order. The results indicate that the plastome sequence of M. peregrina consists of 131 genes, with an average GC content of 39.23%. There is a disparity in the IR regions of the 26 species ranging from 25,804 to 31,477 bp. Plastome structural variations generated 20 hotspot regions that could be considered prospective DNA barcode locations in the Brassicales order. Tandem repeats and SSR structures are reported as significant evidence of structural variations among the 26 tested specimens. Furthermore, selective pressure analysis was performed to estimate the substitution rate within the Moringaceae family, which revealing that the ndhA and accD genes are under positive selective pressure. The phylogenetic analysis of the Brassicales order produced an accurate monophyletic annotation cluster of the Moringaceae and Capparaceae species, offering unambiguous identification without overlapping groups between M. oleifera and M. peregrina, which are genetically strongly associated. Divergence time estimation suggests that the two Moringa species recently diversified, 0.467 Ma. Our findings highlight the first complete plastome of the Egyptian wild-type of M. peregrina, which can be used for determining plastome phylogenetic relationships and systematic evolution history within studies on the Moringaceae family.
Chronic CD27-CD70 costimulation promotes type 1-specific polarization of effector Tregs
Authors: Bowakim-Anta Natalia , Acolty Valérie , Azouz Abdulkader , Yagita Hideo , Leo Oberdan , Goriely Stanislas , Oldenhove Guillaume , Moser Muriel
Published: March 2023

Introduction

Most T lymphocytes, including regulatory T cells, express the CD27 costimulatory receptor in steady state conditions. There is evidence that CD27 engagement on conventional T lymphocytes favors the development of Th1 and cytotoxic responses in mice and humans, but the impact on the regulatory lineage is unknown.

Methods

In this report, we examined the effect of constitutive CD27 engagement on both regulatory and conventional CD4+ T cells in vivo, in the absence of intentional antigenic stimulation.

Results

Our data show that both T cell subsets polarize into type 1 Tconvs or Tregs, characterized by cell activation, cytokine production, response to IFN-γ and CXCR3-dependent migration to inflammatory sites. Transfer experiments suggest that CD27 engagement triggers Treg activation in a cell autonomous fashion.

Conclusion

We conclude that CD27 may regulate the development of Th1 immunity in peripheral tissues as well as the subsequent switch of the effector response into long-term memory.
The unfolding story of dying tumor cells during cancer treatment
Authors: He Sijia , Huang Qian , Cheng Jin
Published: March 2023

Generally, the demise of cancer cells in different ways enables the body to clear these harmful cells. However, cancer cells obtain unlimited replication and immortality from successful circumvention of cell death via various mechanisms. Some evidence suggests that treatment-induced dying tumor cells even promote cancer progression. Notably, therapeutic interventions to harness the immune system against tumor cells have shown complicated influences in clinics. Herein, there is an urgent need to clarify the underlying mechanisms that influence the outcome and regulation of the immune system during cancer treatment. In this review, we provide an account on the cell death modes and the relationship between dying tumor cells with tumor immune microenvironment during cancer treatment, focusing on immunotherapy, from mechanistic standpoint to emerging limitations and future directions.
Amount of antigen, T follicular helper cells and affinity of founder cells shape the diversity of germinal center B cells: A computational study
Authors: Garg Amar K. , Mitra Tanmay , Schips Marta , Bandyopadhyay Arnab , Meyer-Hermann Michael
Published: March 2023

A variety of B cell clones seed the germinal centers, where a selection stringency expands the fitter clones to generate higher affinity antibodies. However, recent experiments suggest that germinal centers often retain a diverse set of B cell clones with a range of affinities and concurrently carry out affinity maturation. Amid a tendency to flourish germinal centers with fitter clones, how several B cell clones with differing affinities can be concurrently selected remains poorly understood. Such a permissive selection may allow non-immunodominant clones, which are often rare and of low-affinity, to somatically hypermutate and result in a broad and diverse B cell response. How the constituent elements of germinal centers, their quantity and kinetics may modulate diversity of B cells, has not been addressed well. By implementing a state-of-the-art agent-based model of germinal center, here, we study how these factors impact temporal evolution of B cell clonal diversity and its underlying balance with affinity maturation. While we find that the extent of selection stringency dictates clonal dominance, limited antigen availability on follicular dendritic cells is shown to expedite the loss of diversity of B cells as germinal centers mature. Intriguingly, the emergence of a diverse set of germinal center B cells depends on high affinity founder cells. Our analysis also reveals a substantial number of T follicular helper cells to be essential in balancing affinity maturation with clonal diversity, as a low number of T follicular helper cells impedes affinity maturation and also contracts the scope for a diverse B cell response. Our results have implications for eliciting antibody responses to non-immunodominant specificities of the pathogens by controlling the regulators of the germinal center reaction, thereby pivoting a way for vaccine development to generate broadly protective antibodies.
T cell co-stimulatory and co-inhibitory pathways in atopic dermatitis
Authors: Zheng Chunjiao , Shi Yuling , Zou Ying
Published: March 2023

The use of immune checkpoint inhibitors (ICIs) targeting the T cell inhibitory pathways has revolutionized cancer treatment. However, ICIs might induce progressive atopic dermatitis (AD) by affecting T cell reactivation. The critical role of T cells in AD pathogenesis is widely known. T cell co-signaling pathways regulate T cell activation, where co-signaling molecules are essential for determining the magnitude of the T cell response to antigens. Given the increasing use of ICIs in cancer treatment, a timely overview of the role of T cell co-signaling molecules in AD is required. In this review, we emphasize the importance of these molecules involved in AD pathogenesis. We also discuss the potential of targeting T cell co-signaling pathways to treat AD and present the unresolved issues and existing limitations. A better understanding of the T cell co-signaling pathways would aid investigation of the mechanism, prognosis evaluation, and treatment of AD.
Resolvin D1/N-formyl peptide receptor 2 ameliorates paclitaxel-induced neuropathic pain through the activation of IL-10/Nrf2/HO-1 pathway in mice
Authors: Su Cun-Jin , Zhang Jiang-Tao , Zhao Feng-Lun , Xu De-Lai , Pan Jie , Liu Tong
Published: March 2023

Introduction

Paclitaxel is a chemotherapy drug that is commonly used to treat cancer, but it can cause paclitaxel-induced neuropathic pain (PINP) as a side effect. Resolvin D1 (RvD1) has been shown to be effective in promoting the resolution of inflammation and chronic pain. In this study, we evaluated the effects of RvD1 on PINP and its underlying mechanisms in mice.

Methods

Behavioral analysis was used to assess the establishment of the PINP mouse model and to test the effects of RvD1 or other formulations on mouse pain behavior. Quantitative real-time polymerase chain reaction analysis was employed to detect the impact of RvD1 on 12/15 Lox, FPR2, and neuroinflammation in PTX-induced DRG neurons. Western blot analysis was used to examine the effects of RvD1 on FPR2, Nrf2, and HO-1 expression in DRG induced by PTX. TUNEL staining was used to detect the apoptosis of DRG neurons induced by BMDM conditioned medium. H2DCF-DA staining was used to detect the reactive oxygen species level of DRG neurons in the presence of PTX or RvD1+PTX treated BMDMs CM.

Results

Expression of 12/15-Lox was decreased in the sciatic nerve and DRG of mice with PINP, suggesting a potential involvement of RvD1 in the resolution of PINP. Intraperitoneal injection of RvD1 promoted pain resolution of PINP in mice. Intrathecal injection of PTX-treated BMDMs induced mechanical pain hypersensitivity in naïve mice, while pretreatment of RvD1 in BMDMs prevented it. Macrophage infiltration increased in the DRGs of PINP mice, but it was not affected by RvD1 treatment. RvD1 increased IL-10 expression in the DRGs and macrophages, while IL-10 neutralizing antibody abolished the analgesic effect of RvD1 on PINP. The effects of RvD1 in promoting IL-10 production were also inhibited by N-formyl peptide receptor 2 (FPR2) antagonist. The primary cultured DRG neurons apoptosis increased after stimulation with condition medium of PTX-treated BMDMs, but decreased after pretreatment with RvD1 in BMDMs. Finally, Nrf2-HO1 signaling was additionally activated in DRG neurons after stimulation with condition medium of RvD1+PTX-treated BMDMs, but these effects were abolished by FPR2 blocker or IL-10 neutralizing antibody.

Discussion

In conclusion, this study provides evidence that RvD1 may be a potential therapeutic strategy for the clinical treatment of PINP. RvD1/FPR2 upregulates IL-10 in macrophages under PINP condition, and then IL-10 activates the Nrf2- HO1 pathway in DRG neurons, relieve neuronal damage and PINP.
The many faces of parasite calreticulin
Authors: Esperante Diego , Flisser Ana , Mendlovic Fela
Published: March 2023

Calreticulin from parasites and its vertebrate hosts share ~50% identity and many of its functions are equally conserved. However, the existing amino acid differences can affect its biological performance. Calreticulin plays an important role in Ca2+ homeostasis and as a chaperone involved in the correct folding of proteins within the endoplasmic reticulum. Outside the endoplasmic reticulum, calreticulin is involved in several immunological functions such as complement inhibition, enhancement of efferocytosis, and immune upregulation or inhibition. Several parasite calreticulins have been shown to limit immune responses and promote infectivity, while others are strong immunogens and have been used for the development of potential vaccines that limit parasite growth. Furthermore, calreticulin is essential in the dialogue between parasites and hosts, inducing Th1, Th2 or regulatory responses in a species-specific manner. In addition, calreticulin participates as initiator of endoplasmic reticulum stress in tumor cells and promotion of immunogenic cell death and removal by macrophages. Direct anti-tumoral activity has also been reported. The highly immunogenic and pleiotropic nature of parasite calreticulins, either as positive or negative regulators of the immune response, render these proteins as valuable tools to modulate immunopathologies and autoimmune disorders, as well as a potential treatment of neoplasms. Moreover, the disparities in the amino acid composition of parasite calreticulins might provide subtle variations in the mechanisms of action that could provide advantages as therapeutic tools. Here, we review the immunological roles of parasite calreticulins and discuss possible beneficial applications.
Immunogenicity, efficacy, and safety of human papillomavirus vaccine: Data from China
Authors: Li Mingzhu , Zhao Chao , Zhao Yun , Li Jingran , Wei Lihui
Published: March 2023

The incidence rate and mortality rate of cervical cancer have steadily increased in young women in China. Therefore, it is critical to improve HPV vaccination rates, particularly for the younger population. There are currently five types of prophylactic vaccines in China: bivalent HPV vaccine (AS04-HPV-16/18), quadrivalent HPV vaccine, 9-valent HPV vaccine, homemade Escherichia coli-produced HPV bivalent vaccine, and Pichia pastoris produced HPV bivalent vaccine. All these five HPV vaccines have completed relevant clinical trials in China, and have been proven to be generally well-tolerated and immunogenic, efficacious against persistent HPV-related infections and genital precancerous lesions (data for 9-valent HPV vaccine is absent), and have demonstrated acceptable safety profiles, as previously shown in global studies. Given that the HPV vaccination rate in China is still very low, additional HPV vaccine coverage is needed to reduce the incidence and mortality rates of cervical cancer.
Multifaceted involvements of Paneth cells in various diseases within intestine and systemically
Authors: Cui Chenbin , Wang Xinru , Li Lindeng , Wei Hongkui , Peng Jian
Published: March 2023

Serving as the guardians of small intestine, Paneth cells (PCs) play an important role in intestinal homeostasis maintenance. Although PCs uniquely exist in intestine under homeostasis, the dysfunction of PCs is involved in various diseases not only in intestine but also in extraintestinal organs, suggesting the systemic importance of PCs. The mechanisms under the participation of PCs in these diseases are multiple as well. The involvements of PCs are mostly characterized by limiting intestinal bacterial translocation in necrotizing enterocolitis, liver disease, acute pancreatitis and graft-vs-host disease. Risk genes in PCs render intestine susceptible to Crohn’s disease. In intestinal infection, different pathogens induce varied responses in PCs, and toll-like receptor ligands on bacterial surface trigger the degranulation of PCs. The increased level of bile acid dramatically impairs PCs in obesity. PCs can inhibit virus entry and promote intestinal regeneration to alleviate COVID-19. On the contrary, abundant IL-17A in PCs aggravates multi-organ injury in ischemia/reperfusion. The pro-angiogenic effect of PCs aggravates the severity of portal hypertension. Therapeutic strategies targeting PCs mainly include PC protection, PC-derived inflammatory cytokine elimination, and substituting AMP treatment. In this review, we discuss the influence and importance of Paneth cells in both intestinal and extraintestinal diseases as reported so far, as well as the potential therapeutic strategies targeting PCs.
Modulation of low-dose ozone and LPS exposed acute mouse lung inflammation by IF1 mediated ATP hydrolysis inhibitor, BTB06584
Authors: Singh Pahul , Aulakh Gurpreet Kaur
Published: March 2023

Ozone and bacterial lipopolysaccharide (LPS) are common air pollutants that are related to high hospital admissions due to airway hyperreactivity and increased susceptibility to infections, especially in children, older population and individuals with underlying conditions. We modeled acute lung inflammation (ALI) by exposing 6-8 week old male mice to 0.005 ppm ozone for 2 h followed by 50 μg of intranasal LPS. We compared the immunomodulatory effects of single dose pre-treatment with CD61 blocking antibody (clone 2C9.G2), ATPase inhibitor BTB06584 against propranolol as the immune-stimulant and dexamethasone as the immune-suppressant in the ALI model. Ozone and LPS exposure induced lung neutrophil and eosinophil recruitment as measured by respective peroxidase (MPO and EPX) assays, systemic leukopenia, increased levels of lung vascular neutrophil regulatory chemokines such as CXCL5, SDF-1, CXCL13 and a decrease in immune-regulatory chemokines such as BAL IL-10 and CCL27. While CD61 blocking antibody and BTB06584 produced maximum increase in BAL leukocyte counts, protein content and BAL chemokines, these treatments induced moderate increase in lung MPO and EPX content. CD61 blocking antibody induced maximal BAL cell death, a markedly punctate distribution of NK1.1, CX3CR1, CD61. BTB06584 preserved BAL cell viability with cytosolic and membrane distribution of Gr1 and CX3CR1. Propranolol attenuated BAL protein, protected against BAL cell death, induced polarized distribution of NK1.1, CX3CR1 and CD61 but presented with high lung EPX. Dexamethasone induced sparse cell membrane distribution of CX3CR1 and CD61 on BAL cells and displayed very low lung MPO and EPX levels despite highest levels of BAL chemokines. Our study unravels ATPase inhibitor IF1 as a novel drug target for lung injury.
P2RX7 signaling drives the differentiation of Th1 cells through metabolic reprogramming for aerobic glycolysis
Authors: Salles Érika Machado de , Raeder Paulo Lisboa , Angeli Claudia Blanes , Santiago Verônica Feijoli , de Souza Cristiane Naffah , Ramalho Theresa , Câmara Niels Olsen Saraiva , Palmisano Giuseppe , Álvarez José Maria , D'Império Lima Maria Regina
Published: March 2023

Introduction

This study provides evidence of how Th1 cell metabolism is modulated by the purinergic receptor P2X7 (P2RX7), a cation cannel activated by high extracellular concentrations of adenosine triphosphate (ATP).

Methods

In vivo analysis was performed in the Plasmodium chabaudi model of malaria in view of the great relevance of this infectious disease for human health, as well as the availability of data concerning Th1/Tfh differentiation.

Results

We show that P2RX7 induces T-bet expression and aerobic glycolysis in splenic CD4+ T cells that respond to malaria, at a time prior to Th1/Tfh polarization. Cell-intrinsic P2RX7 signaling sustains the glycolytic pathway and causes bioenergetic mitochondrial stress in activated CD4+ T cells. We also show in vitro the phenotypic similarities of Th1-conditioned CD4+ T cells that do not express P2RX7 and those in which the glycolytic pathway is pharmacologically inhibited. In addition, in vitro ATP synthase blockade and the consequent inhibition of oxidative phosphorylation, which drives cellular metabolism for aerobic glycolysis, is sufficient to promote rapid CD4+ T cell proliferation and polarization to the Th1 profile in the absence of P2RX7.

Conclusion

These data demonstrate that P2RX7-mediated metabolic reprograming for aerobic glycolysis is a key event for Th1 differentiation and suggest that ATP synthase inhibition is a downstream effect of P2RX7 signaling that potentiates the Th1 response.
Integrated pan-cancer analysis and experimental verification of the roles of tropomyosin 4 in gastric cancer
Authors: Guo Qijing , Zhao Linglin , Yan Nan , Li Yan , Guo Cuiping , Dang Shengyan , Shen Xianliang , Han Jianfang , Luo Yushuang
Published: March 2023

Objective

To investigate the function of tropomyosin 4 (TPM4) using pan-cancer data, especially in gastric cancer (GC), using comprehensive bioinformatics analysis and molecular experiments.

Methods

We used UCSC Xena, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), TIMER2.0, GEPIA, cBioPortal, Xiantao tool, and UALCAN websites and databases for the extraction of pan-cancer data on TPM4. TPM4 expression was investigated with respect to prognosis, genetic alterations, epigenetic alterations, and immune infiltration. RNA22, miRWalk, miRDB, Starbase 2.0, and Cytoscape were used for identifying and constructing the regulatory networks of lncRNAs, miRNAs, and TPM4 in GC. Data from GSCALite, drug bank databases, and Connectivity Map (CMap) were used to analyze the sensitivity of drugs dependent on TPM4 expression. Gene Ontology (GO), enrichment analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), wound healing assays, and (Matrigel) transwell experiments were used to investigate the biological functions of TPM4 in GC.

Result

The findings of the comprehensive pan-cancer analysis revealed that TPM4 has a certain diagnostic and prognosis value in most cancers. Alterations in the expression of TPM4, including duplications and deep mutations, and epigenetic alterations revealed that TPM4 expression is related to the expression of DNA methylation inhibitors and RNA methylation regulators at high concentrations. Besides, TPM4 expression was found to correlate with immune cell infiltration, immune checkpoint (ICP) gene expression, the tumor mutational burden (TMB), and microsatellite instability (MSI). Neoantigens (NEO) were also found to influence its response to immunotherapy. A lncRNA-miRNA -TPM4 network was found to regulate GC development and progression. TPM4 expression was related to docetaxel,5-fluorouracil, and eight small molecular targeted drugs sensitivity. Gene function enrichment analyses revealed that genes that were co-expressed with TPM4 were enriched within the extracellular matrix (ECM)-related pathways. Wound-healing and (Matrigel) transwell assays revealed that TPM4 promotes cell migration and invasion. TPM4, as an oncogene, plays a biological role, perhaps via ECM remodeling in GC.

Conclusions

TPM4 is a prospective marker for the diagnosis, treatment outcome, immunology, chemotherapy, and small molecular drugs targeted for pan-cancer treatment, including GC treatment. The lncRNA-miRNA-TPM4network regulates the mechanism underlying GC progression. TPM4 may facilitate the invasion and migration of GC cells, possibly through ECM remodeling.
Ophthalmic consequences of viral hemorrhagic fevers: Insights from the clinic and laboratory
Authors: Karnam Santi , Huang Ye , Nguyen Nam , Yeh Steven
Published: March 2023

Viral hemorrhagic fevers (VHFs) are a diverse group of RNA virus-mediated systemic diseases with significant morbidity and mortality and represent a significant public health concern. Given the high systemic morbidity and mortality in a number of these entities, delays in diagnosis can lead to downstream public health consequences. Many viral hemorrhagic fevers have ophthalmic manifestations and ophthalmologists thus play a key role in disease recognition and the management of ocular complications associated with specific hemorrhagic fevers. This review summarizes the key ophthalmic consequences of viral hemorrhagic fevers, viral disease pathogenesis, disease findings, and areas of unmet research need.
Variations of phytoplankton chlorophyll in the Bay of Bengal: Impact of climate changes and nutrients from different sources
Authors: Siswanto Eko , Sarker Md. Latifur Rahman , Peter Benny N. , Takemura Toshihiko , Horii Takanori , Matsumoto Kazuhiko , Taketani Fumikazu , Honda Makio C.
Published: March 2023

Phytoplankton biomass, quantified as the concentration of chlorophyll-a (CHL), is the base of the marine food web that supports fisheries production in the Bay of Bengal (BoB). Nutrients from river discharge, the ocean subsurface layer, and the atmosphere have been reported to determine CHL in the BoB. Which source of nutrients mainly determines CHL in different parts of the bay has not been determined. Furthermore, how climate variations influence nutrient inputs from different sources and their impacts on CHL have not been detailed. To address these questions, we used relationships between satellite-derived CHL and in situ river discharge data (a proxy for river-borne nutrients) from 1997 to 2016, physical variables, and modeled dust deposition (DD), a proxy for atmosphere-borne nutrients. Nutrients supplied from the ocean subsurface layer were assessed based on variations in physical parameters (i.e., wind stress curl, sea surface height anomaly, and sea surface temperature). We found that nutrients from the Ganges and Brahmaputra Rivers were important for CHL along the northern coast of the bay. By increasing rainfall and river discharge, La Niña extended high-CHL waters further southward. Nutrients from the ocean subsurface layer determine CHL variations mainly in the southwestern bay. We suggest that the variations in the supply of nutrients from the subsurface layer are related to the generation of mesoscale cyclonic eddies during La Niña, a negative Indian Ocean Dipole, or both. Climate-driven cyclonic eddies together with cyclones can intensify Ekman divergence and synergistically lead to a pronounced increase in CHL in the southwestern bay. Nutrients from the atmosphere mainly determine CHL in the central/eastern BoB. We further suggest that DD in the central/eastern BoB is influenced by ENSO with a 6–7-month time lag. CHL in the central/eastern bay responds to the ENSO 6–7 months after the ENSO peak because of the 6–7-month lag between ENSO and DD. This report provides valuable information needed to plan necessary actions for climate adaptation in local fisheries activities by elucidating how climate variations influence phytoplankton.
Effects of supplemental mixed bile acids on growth performance, body composition, digestive enzyme activities, skin color, and flesh quality of juvenile large yellow croaker (Larimichthys crocea) in soybean oil based diet
Authors: Li Jinbao , Wang Zhen , Cao Xiufei , Wang Jianmin , Gong Ye , Wang Xiuneng , Lai Wencong , Bu Xianyong , Zheng Jichang , Mai Kangsen , Ai Qinghui
Published: March 2023

Now the replacement of fish oil (FO) with vegetable oils (VOs) has been broadly applied in aquatic feed, but studies reported that there were negative effects on growth, skin color, flavor and muscle texture. A 10-week feeding trial was conducted to investigate the effects of dietary mixed bile acids (BA) on growth performance, body composition, digestive enzyme activities, skin color and flesh quality of juvenile large yellow croaker (initial weight, 13.10 ± 0.18 g). Four iso-nitrogenous and iso-lipidic experimental diets were formulated and designated as soybean oil (SO), SO supplemented with 300 (BA300), 600 (BA600), and 1200 (BA1200) mg/kg bile acids. Two hundred and forty fish were randomly allocated into 12 floating net cages (1 m × 1 m × 1.5 m) that were located at marine fishing rafts. Each diet was randomly distributed in triplicate (three replicates per treatment, 20 fish per replicate). Fish were hand-fed to apparent satiation twice daily (05:30 and 17:30) for 10 weeks. Results showed that specific growth rate presented quadratic pattern with supplemental bile acids level, peaking at BA600 group. Meanwhile, feed conversion rate of cultured fish was significantly improved in BA600 group (P < 0.05). The redness (a*) of dorsal and lateral line skin and the yellowness (b*) of abdominal skin showed significantly quadratic pattern with the increase of supplemental BA level (P < 0.05), peaking at BA600 group. In terms of dorsal muscle texture, springiness showed a decreasing trend in significantly linear pattern with the increase of supplemental BA level, bottoming at BA600 group. However, cohesiveness and gumminess were significantly linear increased with the increase of supplemental BA level (P < 0.05). No significant differences were observed in lipase, amylase, and trypsin activities (P > 0.05). Total proportion of muscle n-3LCPUFA showed a linearly increasing trend with the increase of supplemental BA level. Muscle TG content was linearly increased with the increase of supplemental BA level (P < 0.05), and significant differences occurred as compared to fish fed diets with SO when supplemental BA level were reached 600 mg/kg and 1200 mg/kg (P < 0.05). The gene expression of acyl-CoA oxidase (aco) was significantly decreased in fish fed diets supplemented with 600 mg/kg bile acids compared with 300 mg/kg other than those fed diets with SO. In conclusion, these results suggested that mixed bile acids supplemented to SO-based diets could improve feed conversion ratio, skin color and flesh quality to some extent.