bluuebunny/crossref_metadata_2025 huggingface dataset:
A review of process intensified CO2 capture in RPB for sustainability and contribution to industrial net zero
Authors: Shukla Chetna , Mishra Poonam , Dash Sukanta Kumar
Published: April 2023

Carbon dioxide (CO2), a significant greenhouse gas released from power plants and industries, substantially impacts climate change; minimizing it and achieving carbon net zero is essential globally. In the direction of reducing CO2 emissions into the atmosphere, post-combustion carbon capture from large point CO2 emitters by chemical absorption involving the absorption of this gas in a capturing fluid is a commonly used and efficacious mechanism. Researchers have worked on the process using conventional columns. However, process intensification technology is required because of the high capital cost, the absorption column height, and the traditional columns’ low energy efficiency. Rotating packed bed (RPB) process intensification equipment has been identified as a suitable technology for enhanced carbon capture using an absorbing fluid. This article reviews and discusses recent model developments in the post-combustion CO2 capture process intensification using rotating packed beds. In the literature, various researchers have developed steady-state mathematical models regarding mass balance and energy balance equations in gas and liquid phases using ordinary or partial differential equations. Due to the circular shape, the equations are considered in a radial direction and have been solved using a numerical approach and simulated using different software platforms, viz. MATLAB, FORTRAN, and gPROMS. A comparison of various correlations has been presented. The models predict the mole fraction of absorbed CO2 and correspond well with the experimental results. Along with these models, an experimental data review on rotating packed bed is also included in this work.
Review of research on evaluating the ecological security of cultivated land
Authors: He Yinjie , Wu Dafang , Liu Yanyan , Zhu Hong
Published: April 2023

Cultivated land provides fundamental land-related resources, and its ecological security is, thus, an important means of protecting it. The ecological security of cultivated land has emerged as an important and challenging area of research in recent years. In this study, we summarize the progress in research on the evaluation of the ecological security of cultivated land through visual analysis. We review the concepts, characteristics, driving factors, scales and methods of evaluation, technologies, and simulations used in the relevant literature. The results show that while the relevant concept has been preliminarily established, research on the ecological security of cultivated land remains in its infancy, and comprehensive work on the subject is lacking. The Prevalent research has mainly focused on analyzing the current situation, but lacks a dynamic analysis of the driving mechanism of the ecological security of cultivated land based on simulations. This has made it difficult to understand the spatiotemporal mechanism of the ecological security of cultivated land. Future research in the area should discuss the complex driving mechanism of interactions between the social economy system and the ecological system and focus on an integrated model to assess its dynamic spatial and multi-scale characteristics of ecological security of cultivated land because this can inform the theory of protecting cultivated land and the design of plans for land use to mitigate global climate change.
Relationship between plant species diversity and aboveground biomass in alpine grasslands on the Qinghai–Tibet Plateau: Spatial patterns and the factors driving them
Authors: Yang Mingxin , Chen Ang , Zhang Min , Gu Qiang , Wang Yanhe , Guo Jian , Yang Dong , Zhao Yun , Huang Qingdongzhi , Ma Leichao , Yang Xiuchun
Published: April 2023

Alpine grasslands are important ecosystems on the Qinghai–Tibet Plateau and are extremely sensitive to climate change. However, the spatial responses of plant species diversity and biomass in alpine grasslands to environmental factors under the background of global climate change have not been thoroughly characterized. In this study, a random forest model was constructed using grassland ground monitoring data with satellite remote sensing data and environmental variables to characterize the plant species diversity and aboveground biomass of grasslands in the Three-River Headwaters Region within the Qinghai–Tibet Plateau and analyze spatial variation in the relationship between the plant species diversity and aboveground biomass and their driving factors. The results show that (1) the selection of characteristic variables can effectively improve the accuracy of random forest models. The stepwise regression variable selection method was the most effective approach, with an R2 of 0.60 for the plant species diversity prediction model and 0.55 for the aboveground biomass prediction model, (2) The spatial distribution patterns of the plant species diversity and aboveground biomass in the study area were similar, they were both high in the southeast and low in the northwest and gradually decreased from east to west. The relationship between the plant species diversity and aboveground biomass varied spatially, they were mostly positively correlated (67.63%), but they were negatively correlated in areas with low and high values of plant species diversity and aboveground biomass, and (3) Analysis with geodetector revealed that longitude, average annual precipitation, and elevation were the main factors driving variation in the plant species diversity and aboveground biomass relationship. We characterized plant species diversity and aboveground biomass, as well as their spatial relationships, over a large spatial scale. Our data will aid biodiversity monitoring and grassland conservation management, as well as future studies aimed at clarifying the relationship between biodiversity and ecosystem functions.
Genetic legacy of southern Middle Siberian mountain and foothill populations of Scots pine (Pinus sylvestris L.): Diversity and differentiation
Authors: Sheller Marina , Tóth Endre György , Ciocîrlan Elena , Mikhaylov Pavel , Tatarintsev Andrey , Kulakov Sergey , Kulakova Nadezhda , Melnichenko Natalia , Ibe Aleksey , Sukhikh Tatyana , Curtu Alexandru Lucian
Published: April 2023

Scots pine (Pinus sylvestris L.) is a widespread and economically important tree species in Eurasia. Southern Siberian, Scots pine mountain and foothills forests are especially valuable natural objects that help to stabilize environmental conditions. Due to the associated impact of natural and anthropogenic factors, the habitats of the species in southern Siberia are constantly shrinking. In this regard, the study of genetic diversity and structure of Scots pine forests in southern Siberia is very relevant. Here, we studied the genetic diversity and structure of eight Scots pine populations located in southern Middle Siberia (Russia). A high level of genetic diversity (HE = 0.518) was detected in the studied populations. No recent bottleneck effect, isolation by distance or isolation-by-environment were detected. Most genetic diversity was found within populations, while only 7% of genetic diversity occurred among populations. Both STRUCTURE analysis and UPGMA clustering showed two genetic groups. Two populations from the Minusink basin and a population from the Western Sayan Mts. formed the first group and the second group was composed of the other populations from Kuznetsk Alatau Mts., Central Tuva basin and Todzha basin. Our findings suggest that the studied Scots pine populations originate from different gene pools. The pattern of genetic diversity revealed by our study may be useful for the elaboration of conservation measures of genetic resources of Scots pine in southern Middle Siberia.
Taxonomic revision of Physalis in Mexico
Authors: Martínez Mahinda , Vargas-Ponce Ofelia , Zamora-Tavares Pilar
Published: April 2023

Physalis (Solanaceae, Solanoideae) is an American genus of ca. 90 species, with its diversity centered on Mexico. We recognize 61 species within the country, for which we provide a generic morphological description, an artificial key to determine species, and brief descriptions. We include distributions, habitats, diagnostic characters, phenology, and uses. Distribution maps and field photographs are also provided. We include conservation status as evaluated by the IUCN.
MicroRNA-21 and microRNA-148a affects PTEN, NO and ROS in canine leishmaniasis
Authors: De Freitas Jéssica Henrique , Bragato Jaqueline Poleto , Rebech Gabriela Torres , Costa Sidnei Ferro , Dos Santos Marilene Oliveira , Soares Matheus Fujimura , Eugênio Flávia de Rezende , Dos Santos Paulo Sérgio Patto , De Lima Valéria Marçal Felix
Published: April 2023

Canine Visceral leishmaniasis (CanL) poses a severe public health threat in several countries. Disease progression depends on the degree of immune response suppression. MicroRNAs (miRs) modulate mRNA translation into proteins and regulate various cellular functions and pathways associated with immune responses. MiR-21 and miR-148a can alter the parasite load and M1 macrophages are the principal cells in dogs’ leishmanicidal activity. A previous study found increased miR-21 and miR-148a in splenic leukocytes (SL) of dogs with CanL using microarray analysis and in silico analysis identified PTEN pathway targets. PTEN is involved in the immune regulation of macrophages. We measured PTEN and the production of reactive oxygen species (ROS) and nitric oxide (NO) before and after transfection SLs of dogs with CanL with mimic and inhibition of miR-21 and miR-148a. PTEN levels increased, NO and ROS decreased in SLs from dogs with CanL. Inhibition of miRNA-21 resulted in PTEN increase; in contrast, PTEN decreased after miR-148a inhibition. Nitrite (NO2) levels increased after transfection with miR-21 inhibitor but were decreased with miR-148a inhibitor. The increase in miR-21 promoted a reduction in ROS and NO levels, but miR-148a inhibition increased NO and reduced ROS. These findings suggest that miR-21 and miR-148a can participate in immune response in CanL, affecting PTEN, NO, and ROS levels.
Unveiling DNA damage repair-based molecular subtypes, tumor microenvironment and pharmacogenomic landscape in gastric cancer
Authors: Kong Weiqi , Wang Zhiqiang , Wang Bingyi
Published: April 2023

Objective: The current molecular classification system for gastric cancer covers genomic, molecular, and morphological characteristics. Non-etheless, classification of gastric cancer based upon DNA damage repair is still lacking. Here, we defined DNA damage repair-based subtypes across gastric cancer and identified clinicopathological, tumor microenvironment and pharmacogenomic features.

Methods: Unsupervised clustering analysis was executed in the TCGA-STAD cohort based upon the transcriptional expression profiling of DNA damage repair genes. LASSO computational approach was adopted for generating a DNA damage repair-relevant gene signature. The identified subtypes or signature were externally verified in the GSE84426 or GSE84433 cohort. The transcriptional levels of immunomodulators, abundance of immune cells and somatic mutations were measured, respectively. Immunotherapeutic response, and drug sensitivity were investigated. The DNA damage repair-relevant genes were further experimentally verified.

Results: Two DNA damage repair-based subtypes were identified, with the notable heterogeneity in prognostic stratification, tumor microenvironment and somatic mutations. The gene signature was generated for risk stratification and prognostic prediction, which was in relation to immunomodulators and immune cells. High-risk cases were more likely to respond to immunotherapy, with distinct pharmacogenomic landscapes between low- and high-risk groups. Higher levels of PAPPA2, MPO, MAGEA11, DEPP1, CPZ, and COLEC12 and lower level of CYTL1 were proven in gastric cancer cells versus controls. Silencing CYTL1 facilitated intracellular ROS accumulation and suppressed migration in gastric cancer cells.

Conclusion: Collectively, the DNA damage repair-based classification is a suitable complement to existing molecular classification system, and the quantitative gene signature provides a robust tool in selecting specific therapeutic options.
An effective prognostic model for assessing prognosis of non-small cell lung cancer with brain metastases
Authors: Wang Rong , Zhang Xing , He Changshou , Guo Wei
Published: April 2023

Background: Brain metastasis, with an incidence of more than 30%, is a common complication of non-small cell lung cancer (NSCLC). Therefore, there is an urgent need for an assessment method that can effectively predict brain metastases in NSCLC and help understand its mechanism.

Materials and methods: GSE30219, GSE31210, GSE37745, and GSE50081 datasets were downloaded from the GEO database and integrated into a dataset (GSE). The integrated dataset was divided into the training and test datasets. TCGA-NSCLC dataset was regarded as an independent verification dataset. Here, the limma R package was used to identify the differentially expression genes (DEGs). Importantly, the RiskScore model was constructed using univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis. Moreover, we explored in detail the tumor mutational signature, immune signature, and sensitivity to treatment of brain metastases in NSCLC. Finally, a nomogram was built using the rms package.

Results: First, 472 DEGs associated with brain metastases in NSCLC were obtained, which were closely associated with cancer-associated pathways. Interestingly, a RiskScore model was constructed using 11 genes from 472 DEGs, and the robustness was confirmed in GSE test, entire GSE, and TCGA datasets. Samples in the low RiskScore group had a higher gene mutation score and lower immunoinfiltration status. Moreover, we found that the patients in the low RiskScore group were more sensitive to the four chemotherapy drugs. In addition, the predictive nomogram model was able to effectively predict the outcome of patients through appropriate RiskScore stratification.

Conclusion: The prognostic RiskScore model we established has high prediction accuracy and survival prediction ability for brain metastases in NSCLC.
Type 1 interferon mediated signaling is indispensable for eliciting anti-tumor responses by Mycobacterium indicus pranii
Authors: Roy Gargi , Chakraborty Anush , Swami Bharati , Pal Lalit , Ahuja Charvi , Basak Soumen , Bhaskar Sangeeta
Published: April 2023

Introduction

The evolving tumor secretes various immunosuppressive factors that reprogram the tumor microenvironment (TME) to become immunologically cold. Consequently, various immunosuppressive cells like Tregs are recruited into the TME which in turn subverts the anti-tumor response of dendritic cells and T cells.Tumor immunotherapy is a popular means to rejuvenate the immunologically cold TME into hot. Mycobacterium indicus pranii (MIP) has shown strong immunomodulatory activity in different animal and human tumor models and has been approved for treatment of lung cancer (NSCLC) patients as an adjunct therapy. Previously, MIP has shown TLR2/9 mediated activation of antigen presenting cells/Th1 cells and their enhanced infiltration in mouse melanoma but the underlying mechanism by which it is modulating these immune cells is not yet known.

Results

This study reports for the first time that MIP immunotherapy involves type 1 interferon (IFN) signaling as one of the major signaling pathways to mediate the antitumor responses. Further, it was observed that MIP therapy significantly influenced frequency and activation of different subsets of T cells like regulatory T cells (Tregs) and CD8+ T cells in the TME. It reduces the migration of Tregs into the TME by suppressing the expression of CCL22, a Treg recruiting chemokine on DCs and this process is dependent on type 1 IFN. Simultaneously, in a type 1 IFN dependent pathway, it enhances the activation and effector function of the immunosuppressive tumor resident DCs which in turn effectively induce the proliferation and effector function of the CD8+ T cells.

Conclusion

This study also provides evidence that MIP induced pro-inflammatory responses including induction of effector function of conventional dendritic cells and CD8+ T cells along with reduction of intratumoral Treg frequency are essentially mediated in a type 1 IFN-dependent pathway.
The nasal microbiome in patients suffering from non-steroidal anti-inflammatory drugs-exacerbated respiratory disease in absence of corticosteroids
Authors: Bartosik Tina J. , Campion Nicholas J. , Freisl Kilian , Liu David T. , Gangl Katharina , Stanek Victoria , Tu Aldine , Pjevac Petra , Hausmann Bela , Eckl-Dorna Julia , Schneider Sven
Published: April 2023

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease phenotypically classified by the absence (CRSsNP) or presence of nasal polyps (CRSwNP). The latter may also be associated with asthma and hypersensitivity towards non-steroidal anti-inflammatory drugs (NSAID) as a triad termed NSAID-exacerbated respiratory disease (N-ERD). The role of the microbiome in these different disease entities with regard to the underlying inflammatory process and disease burden is yet not fully understood. To address this question, we measured clinical parameters and collected nasal samples (nasal mucosal fluids, microbiome swabs from middle meatus and anterior naris) of patients suffering from CRSsNP (n=20), CRSwNP (n=20) or N-ERD (n=20) as well as from patients without CRS (=disease controls, n=20). Importantly, all subjects refrained from taking local or systemic corticosteroids or immunosuppressants for at least two weeks prior to sampling. The nasal microbiome was analyzed using 16S rRNA gene amplicon sequencing, and levels of 33 inflammatory cytokines were determined in nasal mucosal fluids using the MSD platform. Patients suffering from N-ERD and CRSwNP showed significantly worse smell perception and significantly higher levels of type 2 associated cytokines IL-5, IL-9, Eotaxin and CCL17. Across all 4 patient groups, Corynebacteria and Staphylococci showed the highest relative abundances. Although no significant difference in alpha and beta diversity was observed between the control and the CRS groups, pairwise testing revealed a higher relative abundance of Staphylococci in the middle meatus in N-ERD patients as compared to CRSwNP (p<0.001), CRSsNP (p<0.01) and disease controls (p<0.05) and of Lawsonella in patients suffering from CRSwNP in middle meatus and anterior naris in comparison to CRSsNP (p<0.0001 for both locations) and disease controls (p<0.01 and p<0.0001). Furthermore, we observed a positive correlation of Staphylococci with IL-5 (Pearson r=0.548) and a negative correlation for Corynebacteria and Eotaxin-3 (r=-0.540). Thus, in patients refraining from oral and nasal corticosteroid therapy for at least two weeks known to alter microbiome composition, we did not observe differences in microbiome alpha or beta diversity between various CRS entities and disease controls. However, our data suggest a close association between increased bacterial colonization with Staphylococci and decreased colonization by Corynebacteria as well as increased type 2 inflammation.
Case Report: Severe rebound after withdrawal of fingolimod in a patient with neuromyelitis optica spectrum disorder
Authors: Lin Wei , Chou Chung-Hsing , Yang Fu-Chi , Tsai Chia-Kuang , Lin Yu-Kai , Sung Yueh-Feng
Published: April 2023

Purpose

Fingolimod, an oral treatment for relapsing-remitting multiple sclerosis (RRMS), has been associated with a significant rebound in disease activity after therapy cessation. We described a patient with neuromyelitis optica spectrum disorder (NMOSD) who was previously diagnosed with RRMS and experienced fatal rebound syndrome after cessation of fingolimod.

Case report

A 54-year-old woman, previously diagnosed with RRMS, experienced relapse after orthopedic surgery. The diagnosis was later revised to NMOSD based on a positive aquaporin-4 antibody. Three weeks after converting the immunomodulator from fingolimod to azathioprine, severe disease reactivation was observed. Considering the multiple new and enlarging magnetic resonance imaging lesions, the temporal relationship between fingolimod cessation and symptom onset, and the relatively low possibility of disease reactivation within a short time, the diagnosis of fingolimod withdrawal syndrome was proposed. Although immediate steroid pulse therapy and plasma exchange were performed, the patient eventually died owing to a fulminant clinical course.

Conclusion

Fingolimod withdrawal syndrome is well known in patients with multiple sclerosis (MS). It can also occur in patients with NMOSD. Recognizing patients with NMOSD who present with MS-like manifestations, and avoiding drugs that may be harmful to patients with NMOSD, are important.
Antigen-specificity measurements are the key to understanding T cell responses
Authors: Tippalagama Rashmi , Chihab Leila Y. , Kearns Kendall , Lewis Sloan , Panda Sudhasini , Willemsen Lisa , Burel Julie G. , Lindestam Arlehamn Cecilia S.
Published: April 2023

Antigen-specific T cells play a central role in the adaptive immune response and come in a wide range of phenotypes. T cell receptors (TCRs) mediate the antigen-specificities found in T cells. Importantly, high-throughput TCR sequencing provides a fingerprint which allows tracking of specific T cells and their clonal expansion in response to particular antigens. As a result, many studies have leveraged TCR sequencing in an attempt to elucidate the role of antigen-specific T cells in various contexts. Here, we discuss the published approaches to studying antigen-specific T cells and their specific TCR repertoire. Further, we discuss how these methods have been applied to study the TCR repertoire in various diseases in order to characterize the antigen-specific T cells involved in the immune control of disease.
Association between human papillomavirus infection or immunization and risk for rheumatoid arthritis
Authors: Yang Guangxia , Ren Zeqin , Wang Kai
Published: April 2023

Background

Human papillomavirus (HPV) is a virus primarily transmitted through sexual contact. Little is known about the association between HPV infection or immunization and the risk for rheumatoid arthritis (RA). The purpose of this study was to evaluate whether HPV infection or immunization is related to the risk for RA in adults.

Methods

Data were obtained from the 2007-2016 National Health and Nutrition Examination Survey (NHANES). We developed three independent multivariate logistic regression models to evaluate the association between HPV infection or immunization and the risk for RA in adults.

Results

Finally, we analyzed 15,677 and 8,944 subjects, respectively. In all models, HPV infection was positively associated with an increased prevalence of RA in adults aged 18-59 years, with the highest value of the odds ratio (OR) in model 2 (after weighting: OR 1.095, 95% CI 1.092, 1.097), whereas HPV immunization significantly reduced the prevalence of RA in adults aged 18-59 years, with the lowest OR in model C (after weighting: OR 0.477, 95% CI 0.472, 0.481). These associations persisted after correction for confounders such as age, sex, race, education level, marital status, smoking, diabetes, hypertension, hyperlipidemia, and BMI.

Conclusion

In summary, our study suggests that HPV infection is positively associated with the prevalence of RA in adults, and HPV immunization can reduce the prevalence of RA in adults. However, our findings need more powerful to prove these associations through rigorously designed prospective studies.
The shaping of gut immunity in cirrhosis
Authors: Muñoz Leticia , Caparrós Esther , Albillos Agustín , Francés Rubén
Published: April 2023

Cirrhosis is the common end-stage of chronic liver diseases of different etiology. The altered bile acids metabolism in the cirrhotic liver and the increase in the blood-brain barrier permeability, along with the progressive dysbiosis of intestinal microbiota, contribute to gut immunity changes, from compromised antimicrobial host defense to pro-inflammatory adaptive responses. In turn, these changes elicit a disruption in the epithelial and gut vascular barriers, promoting the increased access of potential pathogenic microbial antigens to portal circulation, further aggravating liver disease. After summarizing the key aspects of gut immunity during homeostasis, this review is intended to update the contribution of liver and brain metabolites in shaping the intestinal immune status and, in turn, to understand how the loss of homeostasis in the gut-associated lymphoid tissue, as present in cirrhosis, cooperates in the advanced chronic liver disease progression. Finally, several therapeutic approaches targeting the intestinal homeostasis in cirrhosis are discussed.
Unique structure of ozoralizumab, a trivalent anti-TNFα NANOBODY® compound, offers the potential advantage of mitigating the risk of immune complex-induced inflammation
Authors: Kyuuma Masanao , Kaku Ayaka , Mishima-Tsumagari Chiemi , Ogawa Bunichiro , Endo Mayumi , Tamura Yunoshin , Ishikura Kei-ichiro , Mima Masashi , Nakanishi Yutaka , Fujii Yasuyuki
Published: April 2023

Biologics have become an important component of treatment strategies for a variety of diseases, but the immunogenicity of large immune complexes (ICs) and aggregates of biologics may increase risk of adverse events is a concern for biologics and it remains unclear whether large ICs consisting of intrinsic antigen and therapeutic antibodies are actually involved in acute local inflammation such as injection site reaction (ISR). Ozoralizumab is a trivalent, bispecific NANOBODY® compound that differs structurally from IgGs. Treatment with ozoralizumab has been shown to provide beneficial effects in the treatment of rheumatoid arthritis (RA) comparable to those obtained with other TNFα inhibitors. Very few ISRs (2%) have been reported after ozoralizumab administration, and the drug has been shown to have acceptable safety and tolerability. In this study, in order to elucidate the mechanism underlying the reduced incidence of ISRs associated with ozoralizumab administration, we investigated the stoichiometry of two TNFα inhibitors (ozoralizumab and adalimumab, an anti-TNFα IgG) ICs and the induction by these drugs of Fcγ receptor (FcγR)-mediated immune responses on neutrophils. Ozoralizumab-TNFα ICs are smaller than adalimumab-TNFα ICs and lack an Fc portion, thus mitigating FcγR-mediated immune responses on neutrophils. We also developed a model of anti-TNFα antibody-TNFα IC-induced subcutaneous inflammation and found that ozoralizumab-TNFα ICs do not induce any significant inflammation at injection sites. The results of our studies suggest that ozoralizumab is a promising candidate for the treatment of RA that entails a lower risk of the IC-mediated immune cell activation that leads to unwanted immune responses.
Immune exposure: how macrophages interact with the nucleus pulposus
Authors: Feng Peng , Che Ying , Gao Chunyu , Zhu Liguo , Gao Jinghua , Vo Nam V.
Published: April 2023

Intervertebral disc degeneration (IDD) is a primary contributor to low back pain. Immune cells play an extremely important role in modulating the progression of IDD by interacting with disc nucleus pulposus (NP) cells and extracellular matrix (ECM). Encased within the annulus fibrosus, healthy NP is an avascular and immune-privileged tissue that does not normally interact with macrophages. However, under pathological conditions in which neovascularization is established in the damaged disc, NP establishes extensive crosstalk with macrophages, leading to different outcomes depending on the different microenvironmental stimuli. M1 macrophages are a class of immune cells that are predominantly pro-inflammatory and promote inflammation and ECM degradation in the NP, creating a vicious cycle of matrix catabolism that drives IDD. In contrast, NP cells interacting with M2 macrophages promote disc tissue ECM remodeling and repair as M2 macrophages are primarily involved in anti-inflammatory cellular responses. Hence, depending on the crosstalk between NP and the type of immune cells (M1 vs. M2), the overall effects on IDD could be detrimental or regenerative. Drug or surgical treatment of IDD can modulate this crosstalk and hence the different treatment outcomes. This review comprehensively summarizes the interaction between macrophages and NP, aiming to highlight the important role of immunology in disc degeneration.
Immunization with a novel mRNA vaccine, TGGT1_216200 mRNA-LNP, prolongs survival time in BALB/c mice against acute toxoplasmosis
Authors: Zhang Yizhuo , Li Dan , Shen Yu , Li Shiyu , Lu Shaohong , Zheng Bin
Published: April 2023

Toxoplasma gondii, a specialized intracellular parasite, causes a widespread zoonotic disease and is a severe threat to social and economic development. There is a lack of effective drugs and vaccines against T. gondii infection. Recently, mRNA vaccines have been rapidly developed, and their packaging materials and technologies are well established. In this study, TGGT1_216200 (TG_200), a novel molecule from T. gondii, was identified using bioinformatic screening analysis. TG_200 was purified and encapsulated with a lipid nanoparticle (LNP) to produce the TG_200 mRNA-LNP vaccine. The immune protection provided by the new vaccine and its mechanisms after immunizing BABL/C mice via intramuscular injection were investigated. There was a strong immune response when mice were vaccinated with TG_200 mRNA-LNP. Elevated levels of anti-T. gondii-specific immunoglobulin G (IgG), and a higher IgG2a-to-IgG1 ratio was observed. The levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), IL-4, and IL-10 were also elevated. The result showed that the vaccine induced a mixture of Th1 and Th2 cells, and Th1-dominated humoral immune response. Significantly increased antigen-specific splenocyte proliferation was induced by TG_200 mRNA-LNP immunization. The vaccine could also induce T. gondii-specific cytotoxic T lymphocytes (CTLs). The expression levels of interferon regulatory factor 8 (IRF8), T-Box 21 (T-bet), and nuclear factor kappa B (NF-κB) were significantly elevated after TG_200 mRNA-LNP immunization. The levels of CD83, CD86, MHC-I, MHC-II, CD8, and CD4 molecules were also higher. The results indicated that TG_200 mRNA-LNP produced specific cellular and humoral immune responses. Most importantly, TG_200 mRNA-LNP immunized mice survived significantly longer (19.27 ± 3.438 days) than the control mice, which died within eight days after T. gondii challenge (P< 0.001). The protective effect of adoptive transfer was also assessed, and mice receiving serum and splenocytes from mice immunized with TG_200 mRNA-LNP showed improved survival rates of 9.70 ± 1.64 days and, 13.40 ± 2.32 days, respectively (P< 0.001). The results suggested that TG_200 mRNA-LNP is a safe and promising vaccine against T. gondii infection.
IgG-based B7-H3xCD3 bispecific antibody for treatment of pancreatic, hepatic and gastric cancer
Authors: Lutz Martina S. , Zekri Latifa , Weßling Laura , Berchtold Susanne , Heitmann Jonas S. , Lauer Ulrich M. , Jung Gundram , Salih Helmut R.
Published: April 2023

T cell-based immunotherapy has significantly improved treatment options for many malignancies. However, despite these and other therapeutic improvements over the last decades, gastrointestinal cancers, in particular pancreatic, hepatic and gastric cancer, are still characterized by high relapse rates and dismal prognosis, with an accordingly high unmet medical need for novel treatment strategies. We here report on the preclinical characterization of a novel bispecific antibody in an IgG-based format termed CC-3 with B7-H3xCD3 specificity. In many cancer entities including pancreatic, hepatic and gastric cancers, B7-H3 (CD276) is overexpressed on tumor cells and also on the tumor vasculature, the latter allowing for improved access of immune effector cells into the tumor site upon therapeutic targeting. We demonstrate that CC-3 induces profound T cell reactivity against various pancreatic, hepatic and gastric cancer cell lines as revealed by analysis of activation, degranulation and secretion of IL2, IFNγ as well as perforin, resulting in potent target cell lysis. Moreover, CC-3 induced efficient T cell proliferation and formation of T cell memory subsets. Together, our results emphasize the potential of CC-3, which is presently being GMP-produced to enable clinical evaluation for treatment of pancreatic, hepatic and gastric cancer.
The efficacy and safety of anti-PD-1/PD-L1 in treatment of glioma: a single-arm meta-analysis
Authors: Zeng Yi-Fan , Wei Xin-Yu , Guo Qi-Hao , Chen Si-Yu , Deng Sheng , Liu Zheng-Zheng , Gong Zhi-Cheng , Zeng Wen-Jing
Published: April 2023

Objective

This meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in patients with glioma.

Methods

PubMed, EMBASE, Web of Science, and the Cochrane library were searched from inception to January 2023 without language restriction. Primary outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). The risk of bias was assessed by subgroup analysis, sensitivity analysis, and publication bias, including funnel plot, Egger’s test, and Begg’s test.

Results

A total of 20 studies involving 2,321 patients were included in this meta-analysis. In the analysis of the included phase III clinical trials, the forest plot showed that PD-1/PD-L1 inhibitors did not improve the OS (HR=1.15, 95% CI: 1.03-1.29, P=0.02, I2 = 14%) and PFS (HR=1.43, 95% CI: 1.03-1.99, P=0.03, I2 = 87%). In the single-arm analysis, the forest plot demonstrated that the 6-month OS was 71% (95% CI: 57%-83%, I2 = 92%), 1-year OS was 43% (95% CI: 33%-54%, I2 = 93%), and the 2-year OS was 27% (95% CI: 13%-44%, I2 = 97%). The pooled estimate of the median OS was 8.85 months (95% CI: 7.33-10.36, I2 = 91%). Furthermore, the result indicated that the 6-month PFS was 28% (95% CI: 18%-40%, I2 = 95%), 1-year PFS was 15% (95% CI: 8%-23%, I2 = 92%), and the 18-month PFS was 10% (95% CI: 3%-20%, I2 = 93%). The pooled estimate of the median PFS was 3.72 months (95% CI: 2.44-5.00, I2 = 99%). For ORR, the pooled estimate of ORR was 10% (95% CI: 2%-20%, I2 = 88%). We further analyzed the incidence of PD-1/PD-L1 inhibitor-related AEs, and the pooled incidence of AEs was 70% (95% CI: 58%-81%, I2 = 94%). The incidence of AEs ≥ grade 3 was 19% (95% CI: 11%-30%, I2 = 94%). The funnel plot for the median PFS and median OS was symmetric with no significant differences in Egger’s test and Begg’s test. The sensitivity analysis revealed that our results were stable and reliable.

Conclusion

The results of this meta-analysis suggest that anti-PD-1/PD-L1 therapy is relatively safe but could not prolong survival in glioma. More randomized controlled trials are needed to confirm our results.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42023396057.
Potential biological contributers to the sex difference in multiple sclerosis progression
Authors: Alvarez-Sanchez Nuria , Dunn Shannon E.
Published: April 2023

Multiple sclerosis (MS) is an immune-mediated disease that targets the myelin sheath of central nervous system (CNS) neurons leading to axon injury, neuronal death, and neurological progression. Though women are more highly susceptible to developing MS, men that develop this disease exhibit greater cognitive impairment and accumulate disability more rapidly than women. Magnetic resonance imaging and pathology studies have revealed that the greater neurological progression seen in males correlates with chronic immune activation and increased iron accumulation at the rims of chronic white matter lesions as well as more intensive whole brain and grey matter atrophy and axon loss. Studies in humans and in animal models of MS suggest that male aged microglia do not have a higher propensity for inflammation, but may become more re-active at the rim of white matter lesions as a result of the presence of pro-inflammatory T cells, greater astrocyte activation or iron release from oligodendrocytes in the males. There is also evidence that remyelination is more efficient in aged female than aged male rodents and that male neurons are more susceptible to oxidative and nitrosative stress. Both sex chromosome complement and sex hormones contribute to these sex differences in biology.
Tuning the immune response: sulfated archaeal glycolipid archaeosomes as an effective vaccine adjuvant for induction of humoral and cell-mediated immunity towards the SARS-CoV-2 Omicron variant of concern
Authors: Renner Tyler M. , Akache Bassel , Stuible Matthew , Rohani Nazanin , Cepero-Donates Yuneivy , Deschatelets Lise , Dudani Renu , Harrison Blair A. , Baardsnes Jason , Koyuturk Izel , Hill Jennifer J. , Hemraz Usha D. , Régnier Sophie , Lenferink Anne E. G. , Durocher Yves , McCluskie Michael J.
Published: April 2023

Liposomes composed of sulfated lactosyl archaeol (SLA) have been shown to be a safe and effective vaccine adjuvant with a multitude of antigens in preclinical studies. In particular, SLA-adjuvanted SARS-CoV-2 subunit vaccines based on trimeric spike protein antigens were shown to be immunogenic and efficacious in mice and hamsters. With the continued emergence of SARS-CoV-2 variants, we sought to evaluate next-generation vaccine formulations with an updated antigenic identity. This was of particular interest for the widespread Omicron variant, given the abundance of mutations and structural changes observed within its spike protein compared to other variants. An updated version of our resistin-trimerized SmT1 corresponding to the B.1.1.529 variant was successfully generated in our Chinese Hamster Ovary (CHO) cell-based antigen production platform and characterized, revealing some differences in protein profile and ACE2 binding affinity as compared to reference strain-based SmT1. We next evaluated this Omicron-based spike antigen for its immunogenicity and ability to generate robust antigen-specific immune responses when paired with SLA liposomes or AddaS03 (a mimetic of the AS03 oil-in-water emulsion adjuvant system found in commercialized SARS-CoV-2 protein vaccines). Immunization of mice with vaccine formulations containing this updated antigen with either adjuvant stimulated neutralizing antibody responses favouring Omicron over the reference strain. Cell-mediated responses, which play an important role in the neutralization of intracellular infections, were induced to a much higher degree with the SLA adjuvant relative to the AddaS03-adjuvanted formulations. As such, updated vaccines that are better capable of targeting towards SARS-CoV-2 variants can be generated through an optimized combination of antigen and adjuvant components.
The application of tie-down gillnet to improve the capture of blackfin flounder (Glyptocephalus stelleri) in a sustainable way
Authors: Kim Seonghun , Kim Hyungseok , Kim Pyungkwan
Published: April 2023

In this study, experimental fishing trials were performed to quantitatively evaluate and compare the fishing performance of trammel nets, tie-down gillnets, and single gillnets used for catching blackfin flounder. A total of eight cruises performed at depths of 100–140 m in the waters near Yangyang, Gangwon-do, Korea. Fisheries laws in Korea currently restrict the use of trammel nets due to concerns about overfishing and bycatch. Tie-down gillnets have a support line that changes their stretched height, thus increasing their catch rate, and are an attractive alternative to trammel nets or single gillnets; unmodified gillnet. Due to a lack of quantitative evaluation of their fishing performance, the performances of these three types of gillnets quantitatively compared. The number and weight of fish, particularly blackfish flounder, caught by each net under similar circumstances were compared. Our results suggest that the fishing performance of trammel nets and tie-down gillnets is much higher than that of single gillnets. Compared to single gillnets, trammel nets performed better by 2.98 times and 2.45 times, in terms of the total number and weight of fish caught, respectively, and tie-down gillnets performed better by 2.09 times and 1.97 times, respectively. In addition, the bycatch rate of tie-down gillnet for immature blackfin flounder with the total length less than 20 centimeters was similar to single gillnet; single gillnet 17.5% of immature blackfin flounder, tie-down 20% of immature blackfin flounder, trammel net 62.5% of immature blackfin flounder. Given that many flat fish such as flounders fall out of the net during the fishing process after being stuck in single gillnets, fishermen hope to use trammel nets. However, the relatively high catch rate of trammel nets likely necessitates restrictions for their use. This study suggests that tie-down gillnets are an option for sustainable fishing practice given that they perform better than single gillnet and reduce bycatch of immature blackfin flounder when compared to trammel nets.
From the shallow to the mesophotic: a characterization of Symbiodiniaceae diversity in the Red Sea NEOM region
Authors: Terraneo Tullia I. , Ouhssain Mustapha , Castano Carolina Bocanegra , Aranda Manuel , Hume Benjamin C. C. , Marchese Fabio , Vimercati Silvia , Chimienti Giovanni , Eweida Ameer A. , Voolstra Christian R. , Jones Burton H. , Purkis Sam J. , Rodrigue Mattie , Benzoni Francesca
Published: April 2023

Introduction

The northern Red Sea has been coined a refuge for reef corals due to the exceptional thermal tolerance of these organisms. With ocean warming threatening coral reefs worldwide, a panoptic characterization of corals living in extreme conditions may provide insights into future responses of corals to environmental change. Among other factors, the genotype of the endosymbiotic algae in the family Symbiodiniaceae has been shown to have major implications on the distribution and resilience of their coral hosts. In this study, we aim at genotyping the Symbiodiniaceae communities associated with three depth generalist and one depth specialist coral species, characterized by the ability to withstand environmental conditions that are apparently limiting for other corals and occurring in a unique geographical region.

Methods

We sampled 50 corals from the northern Saudi Arabian Red Sea and the Gulf of Aqaba, covering a 97 m bathymetric gradient. We used high-throughput ITS2 gene sequencing and recovered different patterns of host–algal associations.

Results and discussion

The majority of the recovered algal genotypes appeared host- and environment-specific, while others were more widely distributed. At large, coral specimens were overwhelmingly associated with symbionts from the genus Cladocopium and specifically with many previously undescribed genotypes. This suggests the selection of specific genotypes, which might confer resistance and/or resilience to their host counterparts. Interestingly, we found a limited association with Durusdinium spp. and other known tolerant taxa in mesophotic corals in the northern Red Sea, but not in the Gulf of Aqaba. The broad absence of Durusdinium spp., typically ascribed to be stress tolerant, warrants further investigation into Symbiodiniaceae species that convey environmental resilience. Our data will serve as a baseline to explore the occurrence of specific symbionts that might be contributing to coral acclimation and adaptation and to assay how biodiversity might be impacted if subjected to increasing stressors.
Distribution and dissolution kinetics of biogenic silica in sediments of the northern South China Sea
Authors: Ma Yuwei , Yang Bin , Zhou Nan , Huang Jin , Liu Su Mei , Zhu Dongdong , Liang Wen
Published: April 2023

The dissolution efficiency of sedssimentary biogenic silica (bSiO2) dramatically affects the regeneration of dissolved silicic acid (dSi) at the sediment-water interface, which is a crucial pathway to maintain Si balance and silicic productivity growth in marine environments. We conducted wet alkaline leach and flow-through experiments to explore the dissolution behaviors of sedimentary bSiO2 in the northern South China Sea (NSCS), one of the largest marginal sea continental shelves. The bSiO2 contents of surface sediments were 0.64 - 2.06%, with an average of 1.04 ± 0.35%, varying with isobath water depth. The solubility of bSiO2 in surface sediments ranged from 227 μmol L-1 to 519 μmol L-1, and the dissolution rate constants varied from 0.67 to 1.53 yr-1 under specific conditions in lab incubation. The correlation between the biogenic materials (bSiO2, OC, and TN) revealed a different preservation pattern of bSiO2 in finer (Φ > ~ 5.5) and coarser (Φ< ~ 5.5) sediments. The high concentration of Al in sea water and “Al – detrital – bSiO2” interactions in sediments significantly interfered with the apparent solubility and dissolution dynamics of bSiO2. We combined the regional characteristics (primary production, bottom current, and resuspension-deposition) and the reconstructed dissolution kinetics of bSiO2 explained the mismatch between the surface (diatom biomass)/(total phytoplankton biomass) ratio and the sedimentary bSiO2/OC ratio, and the mismatch between the surface bSiO2 primary productivity and the bSiO2 sediment records in the NSCS. The resuspension-deposition, the higher reconstructed rate constants (0.94 ± 0.13 yr-1), and the dissolution rate (0.20 ± 0.01 yr-1) were responsible for the lower bSiO2/OC ratio (0.45 ± 0.28) at the inner shelf, and the winnowing process at the outer shelf with the lower reconstructed reactivity (0.30 yr-1) and dissolution rate (0.001 yr-1) led to the good preservation of bSiO2 in the upper slope. Furthermore, through the comparison with other sea areas, the relatively lower reactivity (1.12 ± 0.3 yr-1) of bSiO2 in sediments supported the notion that the NSCS sediments may serve as an important silica sink in the world ocean silica cycle.
Atypical exanthem with acral involvement in adult patients associated with human herpesvirus 7 active replication: A case series
Authors: Michelerio Andrea , Tchich Adi , Vassallo Camilla , Brazzelli Valeria
Published: April 2023

An “atypical exanthem” (AE) is an eruptive skin eruption that differs in morphology and etiology from classical exanthems and is often a reason for urgent medical evaluation. The most frequent cause of AEs is a viral infection, but an accurate etiology cannot be established basing on the sole clinical features. Human herpesviruses (HHV) have been often suspected as etiologic agents or cofactors in atypical rashes. We performed a retrospective analysis of adult patients presenting an atypical exanthem associated with HHV-7 active replication in our center. The charts of patients were reviewed and the demographic, clinical and laboratory data collected. Nine patients (six males and three females) were included in the study, with a mean age of 43 years for men and of 26 years for women. All patients presented active HHV-7 replication in plasma during the rash, which turned negative after the exanthem resolved. The exanthem displayed a maculopapular pattern involving the trunk, limbs and, notably, the acral regions, in six patients. In three cases the exanthem was confined to only the acral sites. In most cases, there was no fever and the inflammatory indices remained unchanged. Antihistamines, topical and systemic corticosteroids were used as treatment, with excellent symptom control. We propose adding skin manifestation associated with HHV-7 to the concept of atypical exanthems, in particular those localized to the acral regions.