bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlling influence of water and ice on eruptive style and edifice construction in the Mount Melbourne Volcanic Field (northern Victoria Land, Antarctica)
Authors: Smellie J. L. , Rocchi S. , Di Vincenzo G.
Published: January 2023

The Mount Melbourne Volcanic Field (MMVF) is part of the West Antarctic Rift System, one of Earth’s largest intra-continental rift zones. It contains numerous small, compositionally diverse (alkali basalt–benmoreite) flank and satellite vents of Late Miocene–Pliocene age (≤12.50 Ma; mainly less than 2.5 Ma). They demonstrate a wide range of morphologies and eruptive mechanisms despite overlapping compositions and elevations, and they occur in a relatively small area surrounding the active Mount Melbourne stratovolcano. The volcanic outcrops fall into several main categories based on eruptive style: scoria cones, tuff cones, megapillow complexes, and shield volcanoes. Using the analysis of lithofacies and appraisal of the internal architectures of the outcrops, we have interpreted the likely eruptive setting for each center and examined the links between the environmental conditions and the resulting volcanic edifice types. Previous investigations assumed a glacial setting for most of the centers but without giving supporting evidence. We demonstrate that the local contemporary environmental conditions exerted a dominant control on the resulting volcanic edifices (i.e., the presence or absence of water, including ice or snow). The scoria cones erupted under dry subaerial conditions. Products of highly explosive hydrovolcanic eruptions are represented by tuff cones. The water involved was mainly glacial (meltwater) but may have been marine in a few examples, based on a comparison of the contrasting internal architectures of tuff cones erupted in confined (glacial) and unconfined (marine, lacustrine) settings. One of the glaciovolcanic tuff cones ceased activity shortly after it began transitioning to a tuya. The megapillow complexes are highly distinctive and have not been previously recognized in glaciovolcanic successions. They are subglacial effusive sequences emplaced as interconnected megapillows, lobes, and thick simple sheet lavas. They are believed to have erupted at moderately high discharge and reduced cooling rates in partially drained englacial vaults under ice, probably several hundred meters in thickness. Finally, several overlapping small shield volcanoes crop out mainly in the Cape Washington peninsula area. They are constructed of previously unrecognized multiple ‘a‘ā lava-fed deltas, erupted in association with a thin draping ice cover c. 50–145 m thick. Our study highlights how effectively water in all its forms (e.g., snow, ice, and any meltwater) or its absence exerts a fundamental control on eruption dynamics and volcano construction. When linked to published ages and40Ar/39Ar dates produced by this study, the new environmental information indicates that the Late Pliocene–Pleistocene landscape was mainly an icefield rather than a persistent topography-drowning ice sheet. Ice thicknesses also generally increased toward the present.
Contribution of deep-earth fluids to the geothermal system: A case study in the Arxan volcanic region, northeastern China
Authors: Cui Yueju , Sun Fengxia , Liu Lei , Xie Chao , Li Jing , Chen Zhi , Li Ying , Du Jianguo
Published: January 2023

Investigations of the hot spring water and gas in the volcanic region are involved in assessing geothermal resources and understanding groundwater circulation, volcano, and earthquake activities. The origins of water and gas of the hot springs, lakes, rivers, and rain in the Arxan volcanic region (AVR), northeastern (NE) China, were investigated by conducting a field survey and geochemical analysis. The low electrical conductivity (40–835 μS/cm) and low total dissolved solids (TDS, 23.83–540.00 mg/L) of the water samples indicate that they are fresh water. δ18O and δD values of the water samples range from −4.1% to −16.0% and from −61.3% to −119.9%, respectively. Enrichment of heavy isotopes in the rainwater and the crater lake waters was caused by evaporation. The component H2O of the water samples predominantly originated from the meteoric water, with less than 1 vol% contributed by deep-earth fluids. Ions in the rain sample were predominantly derived from sea salt and continental aerosol. Ions in the surface water samples had multiple origins (mineral dissolution, atmospheric, and anthropogenic sources). While the ions in the hot spring water were predominantly derived from both the dissolution of rocks and deep-earth fluids, the latter contributed 73%–87% of Cl− and 86%–99% of Na+ to the hot spring waters. Gases from the hot springs were composed of more than 95% N2 and less than 5% O2 and Ar, with 3He/4He ratios of 0.14–1.17 RA (RA=1.4×10−6). Excess N2, Ar, He, and CO2 of the hot springs were mainly derived from both the crust and upper mantle. About 3%–23% of the total He in the bubbling gases from the crater lake waters and hot springs is derived from the mantle, implying a supplement of heat energy from the mantle to the geothermal systems. Significantly, about 12% of the He dissolved in the Budonghe water is derived from the mantle, indicating that plenty of mantle-derived heat transported by deep-earth fluids keeps the river water from freezing. Our results indicate that Cl and Na ions and 3He/4He ratio are the feasible geochemical indicators for source partitioning of geothermal fluids.
Abdominal obesity and dsyglycemia are risk factors for liver fibrosis progression in NAFLD subjects: A population-based study
Authors: Julián María Teresa , Ballesta Sílvia , Pera Guillem , Pérez-Montes de Oca Alejandra , Soldevila Berta , Caballería Llorenç , Morillas Rosa , Expósito Carmen , Martínez–Escudé Alba , Puig-Domingo Manel , Franch-Nadal Josep , Torán Pere , Cusi Kenneth , Julve Josep , Mauricio Dídac , Alonso Núria
Published: January 2023

Objective

To investigate longitudinal changes in the liver stiffness measurement (LSM) in the general adult population without known liver disease and to describe its association with metabolic risk factors, with a special focus on subjects with non-alcoholic fatty liver disease (NAFLD) and dysglycemia.

Material and Methods

A longitudinal adult population-based cohort study was conducted in Catalonia. LSM was measured by transient elastography (TE) at baseline and follow-up (median: 4.2 years). Subgroup with NAFLD and dysglycemia were analyzed. Moderate-to-advanced liver fibrosis was defined as LSM ≥8.0 kPa and LSM ≥9.2 kPa respectively.

Results

Among 1.478 subjects evaluated, the cumulative incidence of LSM ≥8.0 kPa and ≥9.2 kPa at follow-up was 2.8% and 1.9%, respectively. This incidence was higher in NAFLD (7.1% for LSM ≥8.0 kPa and 5% for LSM ≥9.2 kPa) and dysglycemia (6.2% for LSM ≥8.0 kPa and 4.7% for LSM ≥9.2 kPa) subgroups. In the global cohort, the multivariate analyses showed that dysglycemia, abdominal obesity and atherogenic dyslipidemia were significantly associated with progression to moderate-to-advanced liver fibrosis. Female sex was negatively associated. In subjects with NAFLD, abdominal obesity and dysglycemia were associated with changes in LSM to ≥8.0 kPa and ≥9.2 kPa at follow-up. A decline in LSM value to <8 kPa was observed in 64% of those subjects with a baseline LSM ≥8.0 kPa.

Conclusions

In this population study, the presence of abdominal obesity and dysglycemia were the main risk metabolic factors associated with moderate-to-advanced liver fibrosis development over time in general populations as well as in subjects with NAFLD.
Endocrine regulation and metabolic mechanisms of osteopontin in the development and progression of osteosarcoma, metastasis and prognosis
Authors: Shao Zhuce , Bi Shuxiong
Published: January 2023

Osteosarcoma is the most common type of malignant bone tumor, occurring in adolescents and patients over 60. It has a bimodal onset and a poor prognosis, and its development has not yet been fully explained. Osteopontin (OPN) is a high protein consisting of 314 amino acid residues with a negative charge and is involved in many biological activities. OPN is not only an essential part of the regulation of the nervous system and endocrine metabolism of skeletal cells. Still, it is also involved in several other important biological activities, such as the division, transformation, and proliferation of skeletal cells and their associated cells, such as bone tumor cells, including bone marrow mesenchymal stem cells, hematopoietic stem cells, osteoblasts, and osteoclasts. Osteoblasts and osteocytes. Recent studies have shown a strong correlation between OPN and the development and progression of many skeletal diseases, such as osteosarcoma and rheumatoid arthritis. This review aims to understand the mechanisms and advances in the role of OPN as a factor in the development, progression, metastasis, and prognosis of osteosarcoma in an attempt to provide a comprehensive summary of the mechanisms by which OPN regulates osteosarcoma progression and in the hope of contributing to the advancement of osteosarcoma research and clinical treatment.
Correlation between ITGB2 expression and clinical characterization of glioma and the prognostic significance of its methylation in low-grade glioma(LGG)
Authors: Liu He , Wang Jiao , Luo Tao , Zhen Zhiming , Liu Li , Zheng Yalan , Zhang Chaobin , Hu Xiaofei
Published: January 2023

Introduction

Glioma is the most common primary tumor in the brain.Integrin beta 2(ITGB2) is a member of the leukocyte integrin family (leukocyte integrin), participating in lymphocyte recycling and homing, cell adhesion, and cell surface-mediated signal transduction. However, few studies on ITGB2 in gliomas have been reported yet.This study first discussed the relationship between ITGB2 expression and clinical characterization of glioma and the prognostic significance of its methylation in low-grade glioma.

Methods

We collected Clinical data and transcription of glioma patients from TCGA, CGGA, and Rembrant datasets to analyze the differential expression of ITGB2 mRNA in glioma tissues and normal tissues. The box polts to evaluated the expression patterns of ITGB2 in different molecular subtypes. Receiver operating characteristic curve (ROC) were used to evaluate and verify the reliability of the model. Kaplan-Meier survival curves to evaluated the relationship between the level of ITGB2 mRNA expression and overall survival (OS). Using cox regression analysis to verify the ability of ITGB2 as an independent predictor of OS in glioma patients. We use TIMER to analyze and visualize the association between immune infiltration levels and a range of variables. The methylation of GBMLGG patients were obtained from the TCGA database through the biological portal.

Results

ITGB2 can be a potential marker for mesenchymal molecular subtype gliomas. COX regression analysis shows that ITGB2 is an independent predictive marker of OS in malignant glioma patients. Biological processes show that ITGB2 has involved glioma immune-related activities, especially closely related to B cells, CD4+Tcells, macrophages, neutrophils, and dendritic cells. ITGB2 is negatively regulated by ITGB2 methylation, resulting in low expression in LGG tissues. Low expression of ITGB2 and high methylation indicate good OS in patients with LGG. The ITGB2 methylation risk score (ITMRS) obtained from the ITGB2 methylation CpG site can better predict the OS of LGG patients. We used univariate and multivariate cox regression analysis of methylationsites, used the R language predict function to obtain the risk score of these ITGB2 methylation sites(ITMRS).

Discussion

ITGB2 can be used as a potential marker of mesenchymal molecular subtypes of gliomas and as an independent predictive marker of OS in patients with malignant gliomas. The ITMRS we established can be used as an independent prognostic factor for LGG and provide a new idea for the diagnosis and treatment of LGG.
Prolactin receptor signaling: A novel target for cancer treatment - Exploring anti-PRLR signaling strategies
Authors: Standing David , Dandawate Prasad , Anant Shrikant
Published: January 2023

Prolactin (PRL) is a peptide hormone mainly secreted from the anterior pituitary gland. PRL is reported to play a role in pregnancy, mammary gland development, immune modulation, reproduction, and differentiation of islet cells. PRL binds to its receptor PRLR, which belongs to a superfamily of the class I cytokine receptor that has no intrinsic kinase activity. In canonical signaling, PRL binding to PRLR induces downstream signaling including JAK-STAT, AKT and MAPK pathways. This leads to increased cell proliferation, stemness, migration, apoptosis inhibition, and resistance to chemotherapy. PRL-signaling is upregulated in numerous hormone-dependent cancers including breast, prostate, ovarian, and endometrial cancer. However, more recently, the pathway has been reported to play a tumor-promoting role in other cancer types such as colon, pancreas, and hepatocellular cancers. Hence, the signaling pathway is an attractive target for drug development with blockade of the receptor being a potential therapeutic approach. Different strategies have been developed to target this receptor including modification of PRL peptides (Del1-9-G129R-hPRL, G129R-Prl), growth hormone receptor/prolactin receptor bispecific antibody antagonist, neutralizing antibody LFA102, an antibody-drug conjugate (ABBV-176) of the humanized antibody h16f (PR-1594804) and pyrrolobenzodiazepine dimer, a bispecific antibody targeting both PRLR and CD3, an in vivo half-life extended fusion protein containing PRLR antagonist PrlRA and albumin binding domain. There have also been attempts to discover and develop small molecular inhibitors targeting PRLR. Recently, using structure-based virtual screening, we identified a few antipsychotic drugs including penfluridol as a molecule that inhibits PRL-signaling to inhibit PDAC tumor progression. In this review, we will summarize the recent advances in the biology of this receptor in cancer and give an account of PRLR antagonist development for the treatment of cancer.
Intrauterine exposure to di(2-ethylhexyl) phthalate (DEHP) disrupts the function of the hypothalamus-pituitary-thyroid axis of the F1 rats during adult life
Authors: Sousa-Vidal Érica Kássia , Henrique Guilherme , Silva Renata Elen Costa da , Serrano-Nascimento Caroline
Published: January 2023

Introduction

DEHP is an endocrine disruptor widely used in the production of malleable plastics. DEHP exposure was associated with altered hypothalamic-pituitary-thyroid (HPT) axis function. Although previous studies reported deleterious effects of DEHP exposure during the intrauterine period, few studies have evaluated the direct effects triggered by this endocrine disruptor on the offspring animals' thyroid function. This study aimed to investigate the impact of intrauterine exposure to DEHP on the HPT axis function programming of the offspring animals during adulthood.

Methods

Pregnant Wistar rats were orally treated with corn oil or corn oil supplemented with DEHP (0.48 or 4.8 mg/kg/day) throughout the gestational period. The offspring rats were euthanized on the 90th postnatal day. Hypothalamus, pituitary, thyroid, and liver were collected to analyze gene expression and protein content through qPCR and Western Blot. Blood was collected to determine TSH and thyroid hormone levels through fluorometric or chemiluminescence immunoassays.

Results

In the adult F1 female rats, the highest dose of DEHP decreased TSH serum levels. In the thyroid, DEHP reduced the gene expression and/or protein content of NIS, TSHR, TG, TPO, MCT8, NKX2.1, PAX8, and FOXE1. These data are consistent with the reduction in T4 serum levels of the F1 DEHP-exposed female rats. In the liver, DEHP exposure increased the mRNA expression of Dio1 and Ttr, while the highest dose of DEHP reduced the mRNA expression of Ugt1a1 and Ugt1a6. Conversely, in the F1 male adult rats, TSHB expression and TSH serum levels were increased in DEHP-exposed animals. In the thyroid, except for the reduced protein content of TSHR, none of the evaluated genes/proteins were altered by DEHP. TH serum levels were not changed in the DEHP-exposed F1 male rats compared to the control group. Additionally, there were no significant alterations in the expression of hepatic enzymes in these animals.

Discussion/Conclusions

Our results demonstrated, for the first time, that intrauterine exposure to DEHP disrupts the HPT axis function in male and female offspring rats and strongly suggest that DEHP exposure increases the susceptibility of the offspring animals to develop thyroid dysfunctions during adulthood.
Analysis of heat transfer mechanism in supercritical fluids from the aspect of pool heating
Authors: Liu Minyun , Liu Shenghui , Xi Dapeng , Huang Shanfang , Huang Yanping
Published: January 2023

For the special phenomena of heat transfer deterioration or enhancement in supercritical fluid heat transfer, existing research still presents inconsistent opinions. In this study, we perform an analysis of the property changes, and present new understandings for pseudo-boiling theory. More importantly, essential differences between subcritical boiling and supercritical pseudo-boiling are highlighted; the critical factors being thermodynamic instability and stability. For isothermal heating cases, pseudo film boiling can be regarded as an extension of near-critical boiling. Moreover, pseudo nucleate boiling only appears in non-isothermal heating cases and is strongly dependent on the heater geometry, materials, etc. A coupled level-set and volume-of-fluid method is used to simulate the near-critical film boiling of carbon dioxide at pressures of 7.0 and 7.37 MPa. In comparison, supercritical cases at a pressure of 7.5 MPa are the natural convections of single-phase fluid with variable physical properties. The numerical results indicate the similar motions of low-density fluids in subcritical and supercritical cases. All results are consistent with prior experiments, providing a better understanding of the special features of supercritical fluid heat transfer.
A switching control method based on a new model considering parasitic capacitance for LLC
Authors: Han Yetong , Ma Dazhong , An Qingpeng
Published: January 2023

LLC converters are used for linking renewable energy and smart grids. However, the output is higher than the reference caused by its own characteristics, especially in the light load, and the output is limited. A new control method is proposed in this paper based on a new model considering parasitic capacitance, which plays a vital role in keeping the output constant in the light load conditions and widening the output range. In addition, the definition of the light load is given in this paper, which ensures an accurate control. In the switching process, a transition period is set to avoid the components from being damaged due to sudden switching and ensures a smooth output and the stability of the control. Finally, this control method based on the new model is proved valid on a 400 V-36 V-1 kw prototype.
NOx concentration prediction in coal-fired power plant based on CNN-LSTM algorithm
Authors: Yin Zhe , Yang Chunlai , Yuan Xiaolei , Jin Fei , Wu Bin
Published: January 2023

Measuring the nitrogen oxides concentration accurately at the inlet of the selective catalytic reduction denitrification system plays an important role in controlling the nitrogen oxides concentration for coal-fired power plants, and a coupling relationship exists between nitrogen oxides concentration and multiple operational variables. Here, a modeling method based on feature fusion and long short-term memory network is proposed to mine the spatial and temporal coupling relationship between input variables for improving the prediction accuracy. First, the collected data were converted to image-like sequences. Then, the high-dimensional features of image-like sequences were fused by a convolutional neural network, and the spatial coupling features among the variables were mined. Finally, the constructed fusion features were input into the long short-term memory network to further explore the time coupling characteristics among the variables and complete the prediction of nitrogen oxides concentration at the inlet of the selective catalytic reduction denitrification system. The simulation results show that the prediction error of nitrogen oxides concentration at the inlet of selective catalytic reduction denitrification system based on CNN-LSTM model is 15.15% lower than that of traditional LSTM model.
Residential load forecasting based on electricity consumption pattern clustering
Authors: Yu Kun , Cao Jiawei , Chen Xingying , Yang Ziyi , Gan Lei
Published: January 2023

In order to reduce the peak load on the power grid, various types of demand response (DR) programs have been developed rapidly, and an increasing number of residents have participated in the DR. The change in residential electricity consumption behavior increases the randomness of electricity load power, which makes residential load forecasting relatively difficult. Aiming at increasing the accuracy of residential load forecasting, an innovative electricity consumption pattern clustering is implemented in this paper. Six categories of residential load are clustered considering the power consumption characteristics of high-energy-consuming equipment, using the entropy method and criteria importance though intercrieria correlation (CRITIC) method. Next, based on the clustering results, the residential load is predicted by the fully-connected deep neural network (FDNN). Compared with the prediction result without clustering, the method proposed in this paper improves the accuracy of the prediction by 5.21%, which is demonstrated in the simulation.
Safety certification of improved biomass cooking stoves—A test method for tipping, sliding, and spilling stability
Authors: Zhao Nan , Zhang Yixiang , Li Xin , Kimemia David K. , Annegarn Harold J. , Makonese Tafadzwa , Dong Renjie , Zhou Yuguang
Published: January 2023

Usage of inefficient and unsafe cookstoves is a cause of significant health losses and injuries in low-income communities. Efforts to develop and disseminate clean cookstoves have concentrated on optimizing thermal and emission performance, but minimal attention was given to safety aspects. Discussions conducted by the ISO TC285 Technical Committee are ongoing on the derivation of a universal biomass cooking stove standard that aims to guide the development and marketing of products that are safe and efficient with clean burning. Under this, cooking stove safety guidelines addressing a range of hazards have been issued to the community of practice. This work critically addressed the current guideline on cooking stove stability by pointing out the inadequacy of the test and suggesting extra tests for an improved rating of a candidate stove. With a pot and fuel introduced to the research, there may be three different failure modes for various pot and stove combinations, which were tipping, sliding, or spilling. The tests were conducted on an inexpensive purposely built “tiltometer” that allowed testing the angles for stove tipping and sliding, as well as cooking pot sliding and spilling failure. The results indicated that tipping angles for a selected list of modern stoves varied widely based on different shapes and masses, from 18° to 72.2°. Also, the performance of the three different failure modes would place the same stove in different tiers by the current safety protocol. Theoretical geometric calculations for the tipping angle were conducted, and the relative errors were within 2.9%–12.7% for the three different orientations. It is suggested that a revision of the interim stove safety standard should be promoted to incorporate the findings of this study.
The brain-computer analogy—“A special issue”
Authors: Matassi Giorgio , Martinez Pedro
Published: January 2023

In this review essay, we give a detailed synopsis of the twelve contributions which are collected in a Special Issue in Frontiers Ecology and Evolution, based on the research topic “Current Thoughts on the Brain-Computer Analogy—All Metaphors Are Wrong, But Some Are Useful.” The synopsis is complemented by a graphical summary, a matrix which links articles to selected concepts. As first identified by Turing, all authors in this Special Issue recognize semantics as a crucial concern in the brain-computer analogy debate, and consequently address a number of such issues. What is missing, we believe, is the distinction between metaphor and analogy, which we reevaluate, describe in some detail, and offer a definition for the latter. To enrich the debate, we also deem necessary to develop on the evolutionary theories of the brain, of which we provide an overview. This article closes with thoughts on creativity in Science, for we concur with the stance that metaphors and analogies, and their esthetic impact, are essential to the creative process, be it in Sciences as well as in Arts.
Gene therapy for lysosomal storage diseases: Current clinical trial prospects
Authors: Kido Jun , Sugawara Keishin , Nakamura Kimitoshi
Published: January 2023

Lysosomal storage diseases (LSDs) are a group of metabolic inborn errors caused by defective enzymes in the lysosome, resulting in the accumulation of undegraded substrates. LSDs are progressive diseases that exhibit variable rates of progression depending on the disease and the patient. The availability of effective treatment options, including substrate reduction therapy, pharmacological chaperone therapy, enzyme replacement therapy, and bone marrow transplantation, has increased survival time and improved the quality of life in many patients with LSDs. However, these therapies are not sufficiently effective, especially against central nerve system abnormalities and corresponding neurological and psychiatric symptoms because of the blood-brain barrier that prevents the entry of drugs into the brain or limiting features of specific treatments. Gene therapy is a promising tool for the treatment of neurological pathologies associated with LSDs. Here, we review the current state of gene therapy for several LSDs for which clinical trials have been conducted or are planned. Several clinical trials using gene therapy for LSDs are underway as phase 1/2 studies; no adverse events have not been reported in most of these studies. The administration of viral vectors has achieved good therapeutic outcomes in animal models of LSDs, and subsequent human clinical trials are expected to promote the practical application of gene therapy for LSDs.
Genetically determined serum bilirubin level and the risk of heart failure: A mendelian randomization study
Authors: Guan Bo , Yang Mingyan , Shen Xing , Wang Yemei , Liu Yutong , Liu Ruihan , Li Shijun , Cao Jian
Published: January 2023

Background: The association between serum bilirubin level and heart failure (HF) was controversial in previous observational studies and the causal effects of bilirubin on HF have not been investigated. Here, we conducted a Mendelian randomization (MR) study to investigate the associations between genetically determined bilirubin level and HF.

Methods: Summary data on the association of single nucleotide polymorphisms (SNPs) with serum bilirubin levels were obtained from genome-wide association study (GWAS) for individuals of European descent and East Asian descent separately. Statistical data for gene-HF associations were extracted from three databases: the HERMES Consortium (47,309 cases and 930,014 controls), FinnGen study (30,098 cases and 229,612 controls) for European population and Biobank Japan (2,820 HF cases and 192,383 controls) for East Asian population. We applied a two-sample Mendelian randomization framework to investigate the causal association between serum bilirubin and HF.

Results: Findings from our MR analyses showed that genetically determined serum bilirubin levels were not causally associated with HF risk in either European or East Asian population (odds ratio [OR] = 1.01 and 95% confidence interval [CI] = .97–1.05 for HERMES Consortium; OR = 1.01 and 95% CI = .98–1.04 for FinnGen Study; OR = .82, 95% CI: .61–1.10 for Biobank Japan). These results remained unchanged using different Mendelian randomization methods and in sensitivity analyses.

Conclusion: Our study did not find any evidence to support a causal association between serum bilirubin and HF.
SARM suppresses TRIF, TRAF3, and IRF3/7 mediated antiviral signaling in large yellow croaker Larimichthys crocea
Authors: Zhang Jia Xi , Li Ying , Tang Jun Chun , Li Kai Qing , Shen Juan Juan , Liu Chang , Jiang Yong Hua , Zhang Zi Ping , Wang Yi Lei , Zou Peng Fei
Published: January 2023

As a TIR domain-containing molecular, sterile α-and armadillo motif-containing protein (SARM) acts as an adaptor in Toll-like receptor (TLR) signaling, and also plays important roles in mediating apoptosis and neuronal injury. In the present study, the ortholog of SARM, named as Lc-SARM, was cloned and identified in large yellow croaker (Larimichthys crocea). The full-length ORF of Lc-SARM consists of 2,154 bp, encoding a protein of 717 amino acids (aa), which is comprised of an N-terminal ARM domain, two SAM domains, and a C-terminal TIR domain. Confocal microscopy revealed that Lc-SARM was mainly distributed in the cytoplasm, and the mRNA expression level of Lc-SARM was broadly distributed in all the detected organs/tissues, with the highest expression level found in the brain. The expression patterns of Lc-SARM could be induced in response to poly I:C, LPS, PGN stimulations, and Pseudomonas plecoglossicida infection. Notably, although the overexpression of Lc-SARM could significantly induce NF-κB, IRF3, IRF7, and type I IFN promoter activation, whereas the co-expression of Lc-SARM with Lc-TRIF, Lc-TRAF3, Lc-IRF3, or Lc-IRF7 significantly down-regulated the induction of NF-κB, IRF3, IRF7, or type I IFN promoter activation, and suppressed the antiviral effects as well as the downstream antiviral-related genes expression compared to the only overexpression of Lc-TRIF, Lc-TRAF3, Lc-IRF3, or Lc-IRF7. Co-immunoprecipitation (Co-IP) assays also demonstrated that Lc-SARM interacts separately with Lc-TRIF, Lc-TRAF3, Lc-IRF3, and Lc-IRF7. It is thus collectively suggested that Lc-SARM functions as a negative regulator in Lc-TRIF, Lc-TRAF3, and Lc-IRF3/7 involved antiviral signaling.
Humoral and T-cell response 12 months after the first BNT162b2 vaccination in solid organ transplant recipients and controls: Kinetics, associated factors, and role of SARS-CoV-2 infection
Authors: Rezahosseini Omid , Hamm Sebastian Rask , Heftdal Line Dam , Pérez-Alós Laura , Møller Dina Leth , Perch Michael , Madsen Johannes Roth , Hald Annemette , Hansen Cecilie Bo , Armenteros Jose Juan Almagro , Pries-Heje Mia Marie , Hasselbalch Rasmus Bo , Fogh Kamille , Frikke-Schmidt Ruth , Hilsted Linda Maria , Sørensen Erik , Ostrowski Sisse Rye , Harboe Zitta Barrella , Iversen Kasper , Bundgaard Henning , Sørensen Søren Schwartz , Rasmussen Allan , Garred Peter , Nielsen Susanne Dam
Published: January 2023

Introduction

We investigated humoral and T-cell responses within 12 months after first BNT162b2 vaccine in solid organ transplant (SOT) recipients and controls who had received at least three vaccine doses. Furthermore, we compared the immune response in participants with and without previous SARS-CoV-2 infection.

Methods

We included adult liver, lung, and kidney transplant recipients, and controls were selected from a parallel cohort of healthcare workers.

Results

At 12th-month, the IgG geometric mean concentrations (GMCs) (P<0.001), IgA GMCs (P=0.003), and median IFN-γ (P<0.001) were lower in SOT recipients than in controls. However, in SOT recipients and controls with previous infection, the neutralizing index was 99%, and the IgG, and IgA responses were comparable. After adjustment, female-sex (aOR: 3.6, P<0.009), kidney (aOR: 7.0, P= 0.008) or lung transplantation (aOR: 7.5, P= 0.014), and use of mycophenolate (aOR: 5.2, P=0.03) were associated with low IgG non response. Age (OR:1.4, P=0.038), time from transplantation to first vaccine (OR: 0.45, P<0.035), and previous SARS-CoV-2 infection (OR: 0.14, P<0.001), were associated with low IgA non response. Diabetes (OR:2.4, P=0.044) was associated with T-cell non response.

Conclusion

In conclusion, humoral and T-cell responses were inferior in SOT recipients without previous SARS-CoV-2 infection but comparable to controls in SOT recipients with previous infection.
A modifiable universal cotinine-chimeric antigen system of NK cells with multiple targets
Authors: Kang Hee Young , Lee Soo Yun , Kim Hyun Min , Lee Su Ui , Lee Hyunseung , Cho Mi Young , Oh Se-Chan , Kim Seok-Min , Park Hye Sun , Han Eun Hee , Kim Seong-Eun , Kim Hyori , Yoon Suk Ran , Doh Junsang , Chung Junho , Hong Kwan Soo , Choi Inpyo , Kim Tae-Don
Published: January 2023

Natural killer (NK) cells are immune effector cells with outstanding features for adoptive immunotherapy. Immune effector cells with chimeric antigen receptors (CARs) are promising targeted therapeutic agents for various diseases. Because tumor cells exhibit heterogeneous antigen expression and lose cell surface antigen expression during malignant progression, many CARs fixed against only one antigen have limited efficacy and are associated with tumor relapse. To expand the utility of CAR-NK cells, we designed a split and universal cotinine-CAR (Cot-CAR) system, comprising a Cot-conjugator and NK92 cells (α-Cot-NK92 cells) engineered with a CAR containing an anti-Cot-specific single-chain variable fragment and intracellular signaling domain. The efficacy of the Cot-CAR system was assessed in vitro using a cytolysis assay against various tumor cells, and its single- or multiple- utility potential was demonstrated using an in vivo lung metastasis model by injecting A549-Red-Fluc cells. The α-Cot-NK92 cells could switch targets, logically respond to multiple antigens, and tune cytolytic activation through the alteration of conjugators without re-engineering. Therefore the universal Cot-CAR system is useful for enhancing specificity and diversity of antigens, combating relapse, and controlling cytolytic activity. In conclusion, this universal Cot-CAR system reveals that multiple availability and controllability can be generated with a single, integrated system.
A diet enriched in omega-3 PUFA and inulin prevents type 1 diabetes by restoring gut barrier integrity and immune homeostasis in NOD mice
Authors: Lo Conte Marta , Antonini Cencicchio Martina , Ulaszewska Marynka , Nobili Angelica , Cosorich Ilaria , Ferrarese Roberto , Massimino Luca , Andolfo Annapaola , Ungaro Federica , Mancini Nicasio , Falcone Marika
Published: January 2023

Introduction

The integrity of the gut barrier (GB) is fundamental to regulate the crosstalk between the microbiota and the immune system and to prevent inflammation and autoimmunity at the intestinal level but also in organs distal from the gut such as the pancreatic islets. In support to this idea, we recently demonstrated that breakage of GB integrity leads to activation of islet-reactive T cells and triggers autoimmune Type 1 Diabetes (T1D). In T1D patients as in the NOD mice, the spontaneous model of autoimmune diabetes, there are alterations of the GB that specifically affect structure and composition of the mucus layer; however, it is yet to be determined whether a causal link between breakage of the GB integrity and occurrence of autoimmune T1D exists.

Methods

Here we restored GB integrity in the NOD mice through administration of an anti-inflammatory diet (AID- enriched in soluble fiber inulin and omega 3-PUFA) and tested the effect on T1D pathogenesis.

Results

We found that the AID prevented T1D in NOD mice by restoring GB integrity with increased mucus layer thickness and higher mRNA transcripts of structural (Muc2) and immunoregulatory mucins (Muc1 and Muc3) as well as of tight junction proteins (claudin1). Restoration of GB integrity was linked to reduction of intestinal inflammation (i.e., reduced expression of IL-1β, IL-23 and IL-17 transcripts) and expansion of regulatory T cells (FoxP3+ Treg cells and IL-10+ Tr1 cells) at the expenses of effector Th1/Th17 cells in the intestine, pancreatic lymph nodes (PLN) and intra-islet lymphocytes (IIL) of AID-fed NOD mice. Importantly, the restoration of GB integrity and immune homeostasis were associated with enhanced concentrations of anti-inflammatory metabolites of the ω3/ω6 polyunsaturated fatty acids (PUFA) and arachidonic pathways and modifications of the microbiome profile with increased relative abundance of mucus-modulating bacterial species such as Akkermansia muciniphila and Akkermansia glycaniphila.

Discussion

Our data provide evidence that the restoration of GB integrity and intestinal immune homeostasis through administration of a tolerogenic AID that changed the gut microbial and metabolic profiles prevents autoimmune T1D in preclinical models.
Uterine NK cells underexpress KIR2DL1/S1 and LILRB1 in reproductive failure
Authors: Woon Ee Von , Nikolaou Dimitrios , MacLaran Kate , Norman-Taylor Julian , Bhagwat Priya , Cuff Antonia O. , Johnson Mark R. , Male Victoria
Published: January 2023

A significant proportion of recurrent miscarriage, recurrent implantation failure and infertility are unexplained, and these conditions have been proposed to have an etiology of immunological dysfunction at the maternal-fetal interface. Uterine Natural Killer cells (uNK) comprise three subsets and are the most numerous immune cells found in the uterine mucosa at the time of implantation. They are thought to play an important role in successful pregnancy by regulation of extravillous trophoblast (EVT) invasion and spiral artery remodelling. Here, we examine the frequency, phenotype and function of uNK1-3 from the uterine mucosa of 16 women with unexplained reproductive failure compared to 11 controls with no reproductive problems, during the window of implantation. We report that KIR2DL1/S1 and LILRB1 expression is lower in the reproductive failure group for both uNK (total uNK, uNK 2 and 3) and pNK. We also show that degranulation activity is significantly reduced in total uNK, and that TNF-α production is lower in all uNK subsets in the reproductive failure group. Taken together, our findings suggest that reproductive failure is associated with global reduction in expression of uNK receptors important for interaction with HLA-C and HLA-G on EVT during early pregnancy, leading to reduced uNK activation. This is the first study to examine uNK subsets during the window of implantation in women with reproductive failure and will serve as a platform to focus on particular aspects of phenotype and function of uNK subsets in future studies. Further understanding of uNK dysregulation is important to establish potential diagnostic and therapeutic targets in the population of women with unexplained reproductive failure.
Exposure to global change and microplastics elicits an immune response in an endangered coral
Authors: Bove Colleen B. , Greene Katharine , Sugierski Sharla , Kriefall Nicola G. , Huzar Alexa K. , Hughes Annabel M. , Sharp Koty , Fogarty Nicole D. , Davies Sarah W.
Published: January 2023

Global change is increasing seawater temperatures and decreasing oceanic pH, driving declines of coral reefs globally. Coral ecosystems are also impacted by local stressors, including microplastics, which are ubiquitous on reefs. While the independent effects of these global and local stressors are well-documented, their interactions remain less explored. Here, we examine the independent and combined effects of global change (ocean warming and acidification) and microplastics exposures on gene expression (GE) and microbial community composition in the endangered coral Acropora cervicornis. Nine genotypes were fragmented and maintained in one of four experimental treatments: 1) ambient conditions (ambient seawater, no microplastics; AMB); 2) microplastics treatment (ambient seawater, microplastics; MP); 3) global change conditions (warm and acidic conditions, no microplastics; OAW); and 4) multistressor treatment (warm and acidic conditions with microplastics; OAW+MP) for 22 days, after which corals were sampled for genome-wide GE profiling and ITS2 and 16S metabarcoding. Overall A. cervicornis GE responses to all treatments were subtle; however, corals in the multistressor treatment exhibited the strongest GE responses, and genes associated with innate immunity were overrepresented in this treatment. ITS2 analyses confirmed that all coral were associated with Symbiodinium ‘fitti’ and 16S analyses revealed similar microbiomes dominated by the bacterial associate Aquarickettsia, suggesting that these A. cervicornis fragments exhibited remarkably low variability in algal and bacterial community compositions. Future work should focus on functional differences across microbiomes, especially Aquarickettsia and viruses, in these responses. Overall, results suggest that when local stressors are coupled with global change, these interacting stressors present unique challenges to this endangered coral species.
Upper thermal limits and risk of mortality of coastal Antarctic ectotherms
Authors: Carter Mauricio J. , García-Huidobro M. Roberto , Aldana Marcela , Rezende Enrico L. , Bozinovic Francisco , Galbán-Malagón Cristóbal , Pulgar José M.
Published: January 2023

Antarctic marine animals face one of the most extreme thermal environments, characterized by a stable and narrow range of low seawater temperatures. At the same time, the Antarctic marine ecosystems are threatened by accelerated global warming. Determining the upper thermal limits (CTmax) is crucial to project the persistence and distribution areas of the Antarctic marine species. Using thermal death time curves (TDT), we estimated CTmax at different temporal scales from 1 minute to daily and seasonal, the predict vulnerability to the current thermal variation and two potential heatwave scenarios. Our results revealed that CTmax at 1 min are far from the temperature present in the marine intertidal area where our study species, showing Echinoderm species higher CTmax than the Chordata and Arthropods species. Simulations indicated that seasonal thermal variation from the intertidal zone contributed to basal mortality, which increased after considering moderate scenarios of heatwaves (+2°C) in the Shetland Archipelago intertidal zone. Our finding highlighted the relevance of including exposure time explicitly on the CTmax estimates, which deliver closer and more realistic parameters according to the species that may be experiencing in the field.
Pravastatin in preeclampsia: A meta-analysis and systematic review
Authors: Mészáros Balázs , Veres Dániel Sándor , Nagyistók Luca , Somogyi Anikó , Rosta Klára , Herold Zoltán , Kukor Zoltán , Valent Sándor
Published: January 2023

Objective

To review of the efficacy and safety of pravastatin use for prophylaxis and treatment of preeclampsia.

Design

Systematic review and meta-analysis of clinical studies evaluating pravastatin for treatment and/or prophylaxis of preeclampsia.

Data collection

Two independent reviewers systematically searched data from PubMed, Scopus, Web of Science, Cochrane, Embase, and clinicaltrials.gov databases, for studies evaluating pravastatin for prevention of pre-eclampsia.

Results

Fourteen studies were identified, including 1,570 pregnant women who received either pravastatin or placebo, published between 2003 and 2022. From these studies, 5 studies were identified for inclusion in the meta-analysis to evaluate the role of pravastatin use prior to 20 weeks of gestation, to prevent pre-eclampsia, Pravastatin treatment reduced the incidence of preeclampsia by 61% and premature birth by 45%. Among the newborns, there was a 45% reduction in intrauterine growth retardation (IUGR) in the treated group, as well as a 77% reduction in those receiving neonatal intensive care unit (NICU) admissions.

Conclusion

Prophylactic treatment with pravastatin appears to reduce risk of developing pre-eclampsia as well as potentially lowering risk of IUGR, preterm birth, and NICU admission in neonates.
Cecropin D-derived synthetic peptides in the fight against Candida albicans cell filamentation and biofilm formation
Authors: Guevara-Lora Ibeth , Bras Grazyna , Juszczak Magdalena , Karkowska-Kuleta Justyna , Gorecki Andrzej , Manrique-Moreno Marcela , Dymek Jakub , Pyza Elzbieta , Kozik Andrzej , Rapala-Kozik Maria
Published: January 2023

The recent progressive increase in the incidence of invasive fungal infections, especially in immunocompromised patients, makes the search for new therapies crucial in the face of the growing drug resistance of prevalent nosocomial yeast strains. The latest research focuses on the active compounds of natural origin, inhibiting fungal growth, and preventing the formation of fungal biofilms. Antimicrobial peptides are currently the subject of numerous studies concerning effective antifungal therapy. In the present study, the antifungal properties of two synthetic peptides (ΔM3, ΔM4) derived from an insect antimicrobial peptide – cecropin D – were investigated. The fungicidal activity of both compounds was demonstrated against the yeast forms of Candida albicans, Candida tropicalis, and Candida parapsilosis, reaching a MFC99.9 in the micromolar range, while Candida glabrata showed greater resistance to these peptides. The scanning electron microscopy revealed a destabilization of the yeast cell walls upon treatment with both peptides; however, their effectiveness was strongly modified by the presence of salt or plasma in the yeast environment. The transition of C. albicans cells from yeast to filamentous form, as well as the formation of biofilms, was effectively reduced by ΔM4. Mature biofilm viability was inhibited by a higher concentration of this peptide and was accompanied by increased ROS production, activation of the GPX3 and SOD5 genes, and finally, increased membrane permeability. Furthermore, both peptides showed a synergistic effect with caspofungin in inhibiting the metabolic activity of C. albicans cells, and an additive effect was also observed for the mixtures of peptides with amphotericin B. The results indicate the possible potential of the tested peptides in the prevention and treatment of candidiasis.
A new and efficient procedure to load bioactive molecules within the human heavy-chain ferritin nanocage
Authors: Lucignano Rosanna , Stanzione Ilaria , Ferraro Giarita , Di Girolamo Rocco , Cané Carolina , Di Somma Angela , Duilio Angela , Merlino Antonello , Picone Delia
Published: January 2023

For their easy and high-yield recombinant production, their high stability in a wide range of physico-chemical conditions and their characteristic hollow structure, ferritins (Fts) are considered useful scaffolds to encapsulate bioactive molecules. Notably, for the absence of immunogenicity and the selective interaction with tumor cells, the nanocages constituted by the heavy chain of the human variant of ferritin (hHFt) are optimal candidates for the delivery of anti-cancer drugs. hHFt nanocages can be disassembled and reassembled in vitro to allow the loading of cargo molecules, however the currently available protocols present some relevant drawbacks. Indeed, protein disassembly is achieved by exposure to extreme pH (either acidic or alkaline), followed by incubation at neutral pH to allow reassembly, but the final protein recovery and homogeneity are not satisfactory. Moreover, the exposure to extreme pH may affect the structure of the molecule to be loaded. In this paper, we report an alternative, efficient and reproducible procedure to reversibly disassemble hHFt under mild pH conditions. We demonstrate that a small amount of sodium dodecyl sulfate (SDS) is sufficient to disassemble the nanocage, which quantitatively reassembles upon SDS removal. Electron microscopy and X-ray crystallography show that the reassembled protein is identical to the untreated one. The newly developed procedure was used to encapsulate two small molecules. When compared to the existing disassembly/reassembly procedures, our approach can be applied in a wide range of pH values and temperatures, is compatible with a larger number of cargos and allows a higher protein recovery.