bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroacupuncture ameliorates peptic ulcer disease in association with gastroduodenal microbiota modulation in mice
Authors: Li Xiaoshuang , He Feiyu , Tuo Xuan , Qiu Yuanming , Guo Jingjing , Wu Yiming , Meng Xianjun , Yang Zongbao
Published: August 2022

Peptic ulcer disease (PUD) is a common disease and frequently encountered in the clinic. Accumulating evidence suggests that PUD is associated with the gastrointestinal microbiota. Electroacupuncture (EA) is an improved version of acupuncture, which can improve the clinical effect by increasing the stimulation and delivering appropriate electrical pulses to needles. This method has been widely used in the treatment of peptic ulcer disease. However, its effect on gastrointestinal microbiota remains unclear. Therefore, in the present study, the ameliorative effect of EA was evaluated on the gastroduodenal mucosa, and the regulatory effect of the gastroduodenal microbiota was assessed in PUD mice. A total of 48 male Kun Ming mice were randomly divided into the following groups: normal control group (NC), PUD model group (PUD), Shousanli group (LI10), and Zusanli group (ST36) (n=12). The mice in groups LI10 and ST36 were treated with EA at LI10 and ST36, respectively. This intervention was continued for 7 days. Subsequently, we evaluated the morphological changes in the gastric and duodenal mucosa, and specific indices were measured, including the contents of serum dopamine (DA), the trefoil factor (TFF), and the vasoactive intestinal peptide (VIP). In addition, the gastric and duodenal microbiota were assessed via 16S ribosomal DNA sequencing. The results indicated that EA at LI10 or ST36 significantly reduced the injury of the gastroduodenal mucosa in PUD mice. The gastric microbial community structure of the groups LI10 and ST36 was similar to that of the NC group following comparison with the microbial community structure of the PUD model group. Moreover, the abundance of Firmicutes in the stomach was decreased, whereas that of Bacteroidetes was increased, and the abundance of Firmicutes in the duodenum was decreased. Furthermore, the microbial diversity and richness of the gastric microbiota in group LI10 were also significantly increased, and the serum dopamine and trefoil factor levels in group ST36 were significantly increased. Therefore, it is suggested that EA ameliorating PUD is in association with improving the levels of DA and TFF and regulating the relative abundances of Firmicutes and Bacteroidetes in the gastric microbiota.
Characteristics of fractures development and its controlling factors within the buried hill reservoirs from the Archaean metamorphic basement in the Bozhong Sag, Bohai Bay Basin, Eastern China
Authors: Wang Wei , Yi Jian , Shan Xuanlong , Zhang Xintao , Liu Xiaojian , Liu Pengcheng , Ren Shuyue
Published: August 2022

Metamorphic rocks have almost no primary pore space, and their formation of large-scale reservoirs depends on fractures and related secondary pore space formed by tectonic and fluid activities. The BZ19-6 block in the Bozhong Sag, Bohai Bay Basin, is the largest and deepest buried basement condensate field of buried-hill in the world, and its reservoirs are characterized by strong heterogeneity. In this paper, we systematically summarize the characteristics of fracture development, explore the main factors controlling fracture development, establish a fracture development model and clarify the influence of fractures on reservoir quality by using core and microscopic thin section observations, physical property data, imaging logging data and 3D seismic data analysis. The results show that the major types of fractures in the study area are tectonic fractures and dissolution fractures. In particular, the tectonic fractures are widely developed, accounting for 71.7% of the total number of fractures. Migmatization controls the lithological distribution of Archean metamorphic rocks. The migmatitic granite, having the highest degree of migmatization, is the dominant lithology for fracture development because it is rich in brittle minerals, such as feldspar and quartz. Strong compressional orogeny occurred during Indosinian period when many fractures initially developed, which become dominant among the tectonic fractures. Compression-tension-compression multistage tectonic movements characterized the Yanshanian period. During this period, fractures of different degrees formed. The Himalayan period, critical for fracture reconstruction, reactivated the early fractures and promoted the positive influence of atmospheric freshwater and organic acids on fracture reconstruction. Fractures are distributed unevenly in the vertical direction, and fracture-intensive zones are the main development sites for favourable reservoirs because they enhance the porosity and permeability of Archean metamorphic rocks. It means that these fractures can provide effective storage space for oil and gas, which is key for the formation of large-scale reservoirs. In addition, fractures can provide migration channels for organic acids and atmospheric freshwater, which lead to later dissolution, and connect various dispersed dissolution pores to improve the effectiveness of reservoir space.
Propagation path tracing of hydraulically created fractures based on microseismic monitoring
Authors: Hong-lei Liu , Hai-ting Huang , Peng-hai Zhang , Lian-chong Li , Jun-xu Hou , Liao-yuan Zhang , Zi-lin Zhang
Published: August 2022

To evaluate the effect of hydraulic fracturing in a low-permeability reservoir, a propagation path tracing method for hydraulically created fractures was established based on microseismic monitoring data. First, the numerical simulation of the wave propagation process, grid search, and error-weight coefficient method was combined to locate the microseismic source. Then, the moment tensor inversion method was used to determine the tensile angle and source mechanism of hydraulically created fractures. Next, the tensile angle was used as the weight-index to determine the size of the mixed-source mechanism fracture combined with the shear and tensile source size quantization model. Finally, the spatial topological relationship between fractures was determined by comprehensively considering the spatial location and radius of the fractures, to realize the propagation path tracing of hydraulically created fractures. These tracking results can be used as one of the bases for the evaluation of the hydraulic fracturing effect.
Inflammasome activation as a link between obesity and thyroid disorders: Implications for an integrated clinical management
Authors: Le Moli Rosario , Vella Veronica , Tumino Dario , Piticchio Tommaso , Naselli Adriano , Belfiore Antonino , Frasca Francesco
Published: August 2022

Obesity is strongly associated with chronic low-grade inflammation. Obese patients have an increased risk to develop thyroid autoimmunity and to became hypothyroid, suggesting a pathogenetic link between obesity, inflammation and autoimmunity. Moreover, type 2 diabetes and dyslipidemia, also characterized by low-grade inflammation, were recently associated with more aggressive forms of Graves’ ophthalmopathy. The association between obesity and autoimmune thyroid disorders may also go in the opposite direction, as treating autoimmune hyper and hypothyroidism can lead to weight gain. In addition, restoration of euthyroidism by L-T4 replacement therapy is more challenging in obese athyreotic patients, as it is difficult to maintain thyrotropin stimulation hormone (TSH) values within the normal range. Intriguingly, pro-inflammatory cytokines decrease in obese patients after bariatric surgery along with TSH levels. Moreover, the risk of thyroid cancer is increased in patients with thyroid autoimmune disorders, and is also related to the degree of obesity and inflammation. Molecular studies have shown a relationship between the low-grade inflammation of obesity and the activity of intracellular multiprotein complexes typical of immune cells (inflammasomes). We will now highlight some clinical implications of inflammasome activation in the relationship between obesity and thyroid disease.
Decreased level of soluble receptor activator of nuclear factor-κβ ligand (sRANKL) in overweight and obese children
Authors: Erazmus Michał , Rumińska Małgorzata , Witkowska-Sędek Ewelina , Kucharska Anna M. , Stelmaszczyk-Emmel Anna , Majcher Anna , Pyrżak Beata
Published: August 2022

Introduction

Childhood obesity contributes to the development of cardiovascular diseases. The molecular pathway – receptor activator of nuclear factor-κβ ligand (RANKL), its receptor RANK and osteoprotegerin (OPG) - takes part not only in bone metabolism but is also involved in the atherosclerosis process. RANKL stimulates osteogenic differentiation and calcification of vascular smooth cells. The associations between the OPG-sRANKL system and various cardiovascular risk factors were displayed. We aimed to evaluate the relationships between serum sRANKL (soluble RANKL) levels and the OPG/sRANKL ratio with cardiometabolic risk factors in overweight and obese children.

Material and methods

The study included 70 children with overweight and obesity (mean age 13.0 ± 2.8) and 35 age-matched normal weight, healthy peers as a control group. In all patients, anthropometric measurements and laboratory tests were performed. Additionally, an oral glucose tolerance test (OGTT) was made only in overweight and obese children. Atherogenic and insulin resistance indices were calculated.

Results

Overweight and obese children had lower sRANKL levels compared to the control group (median 276.95 vs 325.90, p=0.011), and consequently a higher OPG/sRANKL ratio (0.02 vs 0.01, p = 0.013). The studied children in the lowest quartile of sRANKL levels had higher body weight, Body Mass Index, waist circumference and increased glucose and insulin levels 60 minutes after OGTT and higher uric acid values compared to children in the highest quartile. In multivariable linear regression analysis sRANKL negatively correlated only with uric acid (β = - 0.508, p = 0.041). No association was found for the OPG/sRANKL ratio.

Conclusion

Excess fat mass seems to alter the OPG/RANKL ratio mainly by reducing serum sRANKL levels. The correlation between sRANKL and uric acid may suggest a contribution of the OPG-sRANKL system in the cardiometabolic process, but that observation should be confirmed in future studies.
Patient reported outcome measures in children and adolescents with type 1 diabetes using advanced hybrid closed loop insulin delivery
Authors: Gianini Ana , Suklan Jana , Skela-Savič Brigita , Klemencic Simona , Battelino Tadej , Dovc Klemen , Bratina Nataša
Published: August 2022

Purpose

To determine the impact of advanced hybrid closed - loop (AHCL) insulin delivery on quality of life, metabolic control and time in range (TIR) in youth with type 1 diabetes mellitus (T1DM).

Methods

Twenty-four children and adolescents with T1DM (14 female) aged of 10 to 18 years participated in the study. Mixed methods study design was implemented. Quantitative part of the study was conducted as a longitudinal crossover study with data collection before and at the end of AHCL use. Qualitative data were obtained with modeled interviews of four focus groups before and the end of the period. Clinical data were collected from the electronic medical records.

Results

The use of AHCL significantly improved the quality of life in terms of decreased fear of hypoglycemia (p<0.001), decrease in diabetes-related emotional distress (p<0.001), and increased wellbeing (p=0.003). The mean A1C decreased from 8.55 ± 1.34% (69.9 ± 12.3 mmol/mol) to 7.73 ± 0.42 (61.1 ± 2.2 mmol/mol) (p=0.002) at the end of the study. Mean TIR was 68.22% (± 13.89) before and 78.26 (± 6.29) % (p<0.001) at the end of the study.

Conclusion

The use of advanced hybrid closed loop significantly improved the quality of life and metabolic control in children and adolescents with T1DM.
Assessing soil quality for rehabilitation of salt-affected agroecosystem: A comprehensive review
Authors: Basak Nirmalendu , Rai Arvind Kumar , Sundha Parul , Meena Rameshwar Lal , Bedwal Sandeep , Yadav Rajender Kumar , Sharma Parbodh Chander
Published: August 2022

One billion hectares of land worldwide is affected by several kinds of salinity and associated problems. The soil quality (SQ) in salt-affected soil (SAS) is impaired because of the presence of excess electrolytes, disproportionate Na and Ca in soil solution and exchange phase, rhythmic changes in the hydrological cycle, decreasing soil organic matter, poor vegetative cover, low soil biological activity, and crop residue return. Sodic and saline–sodic soils have the potential to provide alkaline reactions and soil physical constraints to regulate the soil attributes affecting SQ. Because of high spatial variability and rapid temporal changes, selection of simple, robust, low cost, and high-throughput master indicators for assessing SQ is very essential for monitoring the aggradation or degradation of SAS. Therefore, screening the master indicators for developing a minimum dataset for SQ assessment of SAS is an important issue for sustainable management of soil in these agro-ecologies. We captured the SQ indicators for SAS from several ecosystems of different countries and discussed the problems of parameterization for assessing SQ. Improved SQ for optimum soil functioning is needed for confirming agricultural productivity and food security around the globe. This review describes the causes and drivers for sodification/salinization and mechanism-oriented rehabilitation options such as the application of mineral gypsum, flue-gas–desulfurized gypsum, elemental S, acidified biochar, polymer, salt tolerance mechanisms, and other agro-techniques for improving the quality of SAS. Based on the SQ assessment, a suite of site-specific soil management practices are advocated for the greening of SAS and prosperity.
Study the forest, not only the trees: Environmental exposures, not genomes, generate most health disparities
Authors: Thompson Taylor V. , Crocker Katherine C.
Published: August 2022

As sequencing and analysis techniques provide increasingly detailed data at a plummeting cost, it is increasingly popular to seek the answers to medical and public health challenges in the DNA sequences of affected populations. This is methodologically attractive in its simplicity, but a genomics-only approach ignores environmentally mediated health disparities, which are well-documented at multiple national and global scales. While genetic differences exist among populations, it is unlikely that these differences overcome social and environmental factors in driving the gap in health outcomes between privileged and oppressed communities. We advocate for following the lead of communities in addressing their self-identified interests, rather than treating widespread suffering as a convenient natural experiment.
Prognostic and immunological role of cuproptosis-related protein FDX1 in pan-cancer
Authors: Xiao Chen , Yang Linhui , Jin Liangzi , Lin Weiguo , Zhang Faqin , Huang Shixin , Huang Zhijian
Published: August 2022

Background: Cancer is the second cause of death worldwide. Copperoptosis is a new mode of regulated cell death and is strongly associated with metabolic pathways. FDX1 is a key gene that promotes copperoptosis, and its impact on tumor pathogenesis and tumor immune response is indistinct and needs further exploration.

Methods: Data was mined from the Cancer Genome Atlas database, the Broad Institute Cancer Cell Line Encyclopedia database, and the International Cancer Genome Consortium. Survival analyses included the Kaplan–Meier method for calculating the cumulative incidence of survival events and the log-rank method for comparing survival curves between groups. Immune cell infiltration levels were calculated using the Spearman correlation test and correlated with FDX1 expression to assess significance. More correlation analyses between FDX1 expression and mutational markers, such as tumor mutational burden (TMB) and microsatellite instability (MSI), were also examined via Spearman assay to explore the relation between FDX1 expression and the sensitivity of common antitumor drugs.

Results: FDX1 expression was downregulated in most kinds of cancers, and this high expression indicated better overall survival and death-specific survival. For several cancer types, FDX1 expression had a positive correlation with immune cell infiltration, and FDX1 also had a positive correlation with TMB and MSI in some cancer types, linking its expression to the assessment of possible treatment responses.

Conclusion: The correlations between FDX1 expression and cancer in varioustissues, including clear links to cancer survival and prognosis, make FDX1 aninteresting biomarker and potential therapeutic target for cancer surveillance and futureresearch.
Identification of a prognostic model based on costimulatory molecule-related subtypes and characterization of tumor microenvironment infiltration in acute myeloid leukemia
Authors: Mao Yan , Hu Zhengyun , Xu Xuejiao , Xu Jinwen , Wu Chuyan , Jiang Feng , Zhou Guoping
Published: August 2022

Costimulatory molecules have been found to play significant roles in anti-tumor immune responses, and are deemed to serve as promising targets for adjunctive cancer immunotherapies. However, the roles of costimulatory molecule-related genes (CMRGs) in the tumor microenvironment (TME) of acute myeloid leukemia (AML) remain unclear. In this study, we described the CMRG alterations in the genetic and transcriptional fields in AML samples chosen from two datasets. We next evaluated their expression and identified two distinct costimulatory molecule subtypes, which showed that the alterations of CMRGs related to clinical features, immune cell infiltration, and prognosis of patients with AML. Then, a costimulatory molecule-based signature for predicting the overall survival of AML patients was constructed, and the predictive capability of the proposed signature was validated in AML patients. Moreover, the constructed costimulatory molecule risk model was significantly associated with chemotherapeutic drug sensitivity of AML patients. In addition, the identified genes in the proposed prognostic signature might play roles in pediatric AML. CMRGs were found to be potentially important in the AML through our comprehensive analysis. These findings may contribute to improving our understanding of CMRGs in patients with AML, as well as provide new opportunities to assess prognosis and develop more effective immunotherapies.
CD160 Promotes NK Cell Functions by Upregulating Glucose Metabolism and Negatively Correlates With HIV Disease Progression
Authors: Sun Zheng , Li Yidi , Zhang Zining , Fu Yajing , Han Xiaoxu , Hu Qinghai , Ding Haibo , Shang Hong , Jiang Yongjun
Published: August 2022

Natural killer (NK) cells are crucial for immune responses to viral infections. CD160 is an important NK cell activating receptor, with unknown function in HIV infection. Here, we found that CD160 expression was reduced on NK cells from HIV-infected individuals and its expression was negatively correlated with HIV disease progression. Further, GLUT1 expression and glucose uptake were higher in CD160+NK cells, and the results of RNA-seq and flow cytometry demonstrated that CD160 positively regulated glucose metabolism through the PI3K/AKT/mTOR/s6k signaling pathway, thereby enhancing NK cell function. Moreover, we determined that reduced CD160 expression on NK cells could be attributed to the higher plasma levels of TGF-β1 in HIV-infected individuals. Overall, these results highlight the vital role of CD160 in HIV disease progression and regulation of glucose metabolism, indicating a potential target for HIV immunotherapy.
Interleukin-7 receptor signaling is crucial for enhancer-dependent TCRδ germline transcription mediated through STAT5 recruitment
Authors: Rodríguez-Caparrós Alonso , Tani-ichi Shizue , Casal Áurea , López-Ros Jennifer , Suñé Carlos , Ikuta Koichi , Hernández-Munain Cristina
Published: August 2022

γδ T cells play important roles in immune responses by rapidly producing large quantities of cytokines. Recently, γδ T cells have been found to be involved in tissue homeostatic regulation, playing roles in thermogenesis, bone regeneration and synaptic plasticity. Nonetheless, the mechanisms involved in γδ T-cell development, especially the regulation of TCRδ gene transcription, have not yet been clarified. Previous studies have established that NOTCH1 signaling plays an important role in theTcrgandTcrdgermline transcriptional regulation induced by enhancer activation, which is mediated through the recruitment of RUNX1 and MYB. In addition, interleukin-7 signaling has been shown to be required forTcrggermline transcription, VγJγ rearrangement and γδ T-lymphocyte generation as well as for promoting T-cell survival. In this study, we discovered that interleukin-7 is required for the activation of enhancer-dependentTcrdgermline transcription during thymocyte development. These results indicate that the activation of bothTcrgandTcrdenhancers during γδ T-cell development in the thymus depends on the same NOTCH1- and interleukin-7-mediated signaling pathways. Understanding the regulation of theTcrdenhancer during thymocyte development might lead to a better understanding of the enhancer-dependent mechanisms involved in the genomic instability and chromosomal translocations that cause leukemia.
Effects of ibrutinib on T-cell immunity in patients with chronic lymphocytic leukemia
Authors: Liu Yanyan , Song Yongping , Yin Qingsong
Published: August 2022

Chronic lymphocytic leukemia (CLL), a highly heterogeneous B-cell malignancy, is characterized by tumor microenvironment disorder and T-cell immune dysfunction, which play a major role in the proliferation and survival of CLL cells. Ibrutinib is the first irreversible inhibitor of Bruton’s tyrosine kinase (BTK). In addition to targeting B-cell receptor (BCR) signaling to kill tumor cells, increasing evidence has suggested that ibrutinib regulates the tumor microenvironment and T-cell immunity in a direct and indirect manner. For example, ibrutinib not only reverses the tumor microenvironment by blocking cytokine networks and toll-like receptor signaling but also regulates T cells in number, subset distribution, T-cell receptor (TCR) repertoire and immune function by inhibiting interleukin-2 inducible T-cell kinase (ITK) and reducing the expression of inhibitory receptors, and so on. In this review, we summarize the current evidence for the effects of ibrutinib on the tumor microenvironment and cellular immunity of patients with CLL, particularly for the behavior and function of T cells, explore its potential mechanisms, and provide a basis for the clinical benefits of long-term ibrutinib treatment and combined therapy based on T-cell-based immunotherapies.
Identification of cuproptosis-related subtypes, characterization of tumor microenvironment infiltration, and development of a prognosis model in breast cancer
Authors: Li Zhi , Zhang Hua , Wang Xixi , Wang Qun , Xue Jiapeng , Shi Yun , Wang Minghua , Wang Geng , Zhang Jianquan
Published: August 2022

Breast cancer (BC) is now the most frequent and lethal cancer among women. Cuproptosis is a newly identified programmed cell death process that has been connected to tumor therapeutic sensitivity, patient outcomes, and the genesis of cancer. Cuproptosis-related genes (CRGs) are involved in breast cancer, although their roles and potential mechanisms are still unclear. First, we examined the effect of gene mutations and copy number changes on overall survival in 1168 breast cancer samples. Breast cancer patients were split into two molecular categories as determined by the variation in CRG based on clinicopathological traits, overall survival, and cell-infiltrating traits in tumor microenvironments. In addition, we created and validated a CRG score to calculate breast cancer patients' OS. Finally, we created a comprehensive nomogram for the clinical use of the CRG score. Patients whose CRG scores were low showed increased odds of developing OS, a larger mutation load, and immunological activation than those with high CRG scores. The CRG score, the cancer stem cell index, and the responsiveness to chemotherapy or targeted therapies were also shown to be statistically significantly correlated. Our thorough examination of CRGs in breast cancer patients demonstrated that they may be useful predictors of prognosis, clinical characteristics, and tumor microenvironment. These findings provide fresh insight into CRGs in breast cancer and might inspire brand-new approaches to both diagnosing and treating patients there.
Fishery resource monitoring of the East China Sea via environmental DNA approach: a case study using black sea bream (Acanthopagrus schlegelii)
Authors: Zhang Haobo , Zhou Yongdong , Zhang Hongliang , Gao Tianxiang , Wang Xiaoyan
Published: August 2022

Understanding fish stock distribution is crucial in the context of sustainable fishery development. Traditional approaches such as net catching, mark recapturing, and visual counting are often time-consuming, less effective, and prone to subjective bias. Recently, environmental DNA (eDNA) technology has made up for the shortcomings of traditional fishery resource survey methods and has been widely used for species monitoring, biodiversity assessment, and biomass estimation. In this study, the eDNA method was used to analyze the potential distribution range of the black sea bream (Acanthopagrus schlegelii) in the East China Sea. The black sea bream-specific primers and probe were designed and applied in the current study. Results showed high black sea bream eDNA concentrations in Dasha fishing ground, Yangtze Estuary fishing ground, and Zhoushan fishing ground. Higher concentrations of black sea bream eDNA were found in water depths approximately 30–40 m. The eDNA hotspots were mainly concentrated at 29°N–33°N, 122°E–125°E, but no significant differences in horizontal or vertical distributions were observed. Temperature is a critical factor in the presence and black sea bream eDNA among environmental variables in the correlation analysis. In addition, a linear formula between environmental factors and the black sea bream eDNA concentration of black sea bream was predicted, which may be helpful for future fishery resource surveys. To summarize, the present paper provides a new idea for marine resource surveys. It also affords a method and theoretical basis for applying the eDNA technology in fishery surveys, which is expected to become an essential tool for fishery resource surveys in the future.
Effects of graphene content on the microstructure and mechanical properties of alumina-based composites
Authors: Zhu Jun , Jia Bi , Di Yongjiang , Liu Biao , Wan Xin , Wang Wenrong , Tang Rui , Liao Shu , Chen Xingyu
Published: August 2022

In this work, alumina-graphene (Al2O3-G) composites with graphene contents ranging from 0.5 to 3% were prepared by stepwise feeding ball milling and hot pressing. The influences of graphene content on the microstructure and mechanical properties of Al2O3-G composites were investigated. Results showed that the densification, grain sizes, flexural strength, fracture toughness and Vickers hardness of materials increased firstly and then decreased with increasing graphene contents. When the graphene content was 1%, the value of each performance parameter reached the maximum. The average grain size of material decreased from 991 to 551 nm as the graphene content increased from 0 to 1%, but it increased to 863 nm when the graphene content was 3%. The flexural strength, fracture toughness and Vickers hardness of composites with graphene content of 1% increased to 763.5 MPa, 7.4 MPa m1/2 and 21.28 GPa. Compared with the Al2O3, the fracture strength and toughness of the composites increased by up to 54.63 and 65.54%. Analysis suggested that the strength of Al2O3-G composites was mainly related to the grain size and preexisting microflaws.
Disease mechanisms in preclinical rheumatoid arthritis: A narrative review
Authors: Romão Vasco C. , Fonseca João Eurico
Published: August 2022

In the last decades, the concept of preclinical rheumatoid arthritis (RA) has become established. In fact, the discovery that disease mechanisms start years before the onset of clinical RA has been one of the major recent insights in the understanding of RA pathogenesis. In accordance with the complex nature of the disease, preclinical events extend over several sequential phases. In a genetically predisposed host, environmental factors will further increase susceptibility for incident RA. In the initial steps of preclinical disease, immune disturbance mechanisms take place outside the joint compartment, namely in mucosal surfaces, such as the lung, gums or gut. Herein, the persistent immunologic response to altered antigens will lead to breach of tolerance and trigger autoimmunity. In a second phase, the immune response matures and is amplified at a systemic level, with epitope spreading and widening of the autoantibody repertoire. Finally, the synovial and bone compartment are targeted by specific autoantibodies against modified antigens, initiating a local inflammatory response that will eventually culminate in clinically evident synovitis. In this review, we discuss the elaborate disease mechanisms in place during preclinical RA, providing a broad perspective in the light of current evidence.
Increased histone citrullination in juvenile idiopathic arthritis
Authors: Parackova Zuzana , Zentsova Irena , Malcova Hana , Cebecauerova Dita , Sediva Anna , Horvath Rudolf
Published: August 2022

Objective

Posttranslational modifications (PTMs) of proteins are crucial for regulating various biological processes. However, protein alteration via PTMs, and consequently, the creation of new epitopes, can induce abnormal autoimmune responses in predisposed individuals. Immunopathogenesis of several rheumatic diseases, including the most common childhood form, juvenile idiopathic arthritis (JIA), is associated with the generation of autoantibodies against such modified proteins. Dysregulated generation of neutrophil extracellular traps (NETs) can be a source of post-translationally altered proteins. Thus, we investigated the role of PTMs and the presence of NET-associated markers in JIA patients.

Methods

We recruited 30 pediatric patients with JIA (20 with active disease and 10 in remission) and 30 healthy donors. The serum concentrations of citrullinated histone H3 (citH3), peptidyl arginine deiminases (PADs), and NET-related products were detected using ELISA, and the number of citH3+ neutrophils was assessed using flow cytometry.

Results

The serum levels of citH3 and PADs were higher in active as well as in remission JIA patients than in healthy donors. Similarly, the number of citH3+ neutrophils was higher in the peripheral blood of patients with JIA, implying an enhanced process of NETosis. This was effectively reflected by elevated serum levels of NET-associated products, such as neutrophil elastase, LL37, and cell-free DNA-histone complexes. Additionally, 16.7% of active JIA patients were seropositive for carbamylated autoantibodies, the levels of which declined sharply after initiation of anti-TNFα therapy.

Conclusion

Collectively, our data suggest that the accelerated process of NETosis and PTMs in JIA may result in the generation of anti-citrullinated/carbamylated autoantibodies against various epitopes later in life, which could be prevented by effectively regulating inflammation using immune therapy.
Relationship between cytokine release and stress hyperglycemia in patients hospitalized with COVID-19 infection
Authors: Da Porto Andrea , Tascini Carlo , Colussi Gianluca , Peghin Maddalena , Graziano Elena , De Carlo Chiara , Bulfone Luca , Antonello Martina , Sozio Emanuela , Fabris Martina , Curcio Francesco , Pucillo Carlo , Catena Cristiana , Sechi Leonardo A.
Published: August 2022

Introduction

Stress hyperglycemia is a frequent finding in patients with COVID-19 infection and could affect the outcome of disease. Cytokines released in response to infection could have adverse effects on insulin sensitivity and pancreatic beta-cell function. The aim of the study was to examine the relationships of stress hyperglycemia with cytokines and clinical outcomes in hospitalized patients with COVID-19.

Methods

In a cross-sectional analysis of 150 patients hospitalized for COVID-19 infection who were included in the GIRA-COVID database, we identified patients with stress hyperglycemia by calculation of the Stress Hyperglycemia Ratio (SHR) and use of a cut-off of 1.14. Plasma levels of cytokines principally involved in COVID-19 infection-related cytokine storm were measured. Outcome variables were use of mechanical ventilation and death within 60 days from hospital admission.

Results

Patients with SHR > 1.14 had significantly higher plasma insulin, HOMA-index, and levels of interleukin-10 (IL-10), interleukin-10/tumor necrosis factor-a ratio (IL-10/TNF-α), and CXC motif chemokine ligand 10 (CXCL10) than patients with SHR ≤ 1.14. IL-10, IL-10/TNF-α ratio, CXCL10, and IFN-γ were significantly and directly related with SHR in univariate analysis and multivariate logistic regression models showed that IL-10, IL-10/TNF-α ratio, and CXCL10 were independently associated with SHR>1.14. In a multivariate logistic model, stress hyperglycemia predicted use of mechanical ventilation (OR 2.453; CI 1.078–6.012) and death (OR 2.281; CI 1.049–7.369) independently of diabetes and other major confounders.

Conclusions

In patients hospitalized for COVID-19 infection, stress hyperglycemia is associated with worse clinical outcomes and is independently related to levels of cytokines that might impair glucose homeostasis.
Preparation of RNAs with non-canonical 5′ ends using novel di- and trinucleotide reagents for co-transcriptional capping
Authors: Depaix Anaïs , Grudzien-Nogalska Ewa , Fedorczyk Bartlomiej , Kiledjian Megerditch , Jemielity Jacek , Kowalska Joanna
Published: August 2022

Many eukaryotic and some bacterial RNAs are modified at the 5′ end by the addition of cap structures. In addition to the classic 7-methylguanosine 5′ cap in eukaryotic mRNA, several non-canonical caps have recently been identified, including NAD-linked, FAD-linked, and UDP-glucose-linked RNAs. However, studies of the biochemical properties of these caps are impaired by the limited access to in vitro transcribed RNA probes of high quality, as the typical capping efficiencies with NAD or FAD dinucleotides achieved in the presence of T7 polymerase rarely exceed 50%, and pyrimidine derivatives are not incorporated because of promoter sequence limitations. To address this issue, we developed a series of di- and trinucleotide capping reagents and in vitro transcription conditions to provide straightforward access to unconventionally capped RNAs with improved 5′-end homogeneity. We show that because of the transcription start site flexibility of T7 polymerase, R1ppApG-type structures (where R1 is either nicotinamide riboside or riboflavin) are efficiently incorporated into RNA during transcription from dsDNA templates containing both φ 6.5 and φ 2.5 promoters and enable high capping efficiencies (∼90%). Moreover, uridine-initiated RNAs are accessible by transcription from templates containing the φ 6.5 promoter performed in the presence of R2ppUpG-type initiating nucleotides (where R2 is a sugar or phosphate moiety). We successfully employed this strategy to obtain several nucleotide-sugar-capped and uncapped RNAs. The capping reagents developed herein provide easy access to chemical probes to elucidate the biological roles of non-canonical RNA 5′ capping.
Exploring the eukaryotic Yip and REEP/Yop superfamily of membrane-shaping adapter proteins (MSAPs): A cacophony or harmony of structure and function?
Authors: Angelotti Timothy
Published: August 2022

Polytopic cargo proteins are synthesized and exported along the secretory pathway from the endoplasmic reticulum (ER), through the Golgi apparatus, with eventual insertion into the plasma membrane (PM). While searching for proteins that could enhance cell surface expression of olfactory receptors, a new family of proteins termed “receptor expression-enhancing proteins” or REEPs were identified. These membrane-shaping hairpin proteins serve as adapters, interacting with intracellular transport machinery, to regulate cargo protein trafficking. However, REEPs belong to a larger family of proteins, the Yip (Ypt-interacting protein) family, conserved in yeast and higher eukaryotes. To date, eighteen mammalian Yip family members, divided into four subfamilies (Yipf, REEP, Yif, and PRAF), have been identified. Yeast research has revealed many intriguing aspects of yeast Yip function, functions that have not completely been explored with mammalian Yip family members. This review and analysis will clarify the different Yip family nomenclature that have encumbered prior comparisons between yeast, plants, and eukaryotic family members, to provide a more complete understanding of their interacting proteins, membrane topology, organelle localization, and role as regulators of cargo trafficking and localization. In addition, the biological role of membrane shaping and sensing hairpin and amphipathic helical domains of various Yip proteins and their potential cellular functions will be described. Lastly, this review will discuss the concept of Yip proteins as members of a larger superfamily of membrane-shaping adapter proteins (MSAPs), proteins that both shape membranes via membrane-sensing and hairpin insertion, and well as act as adapters for protein-protein interactions. MSAPs are defined by their localization to specific membranes, ability to alter membrane structure, interactions with other proteins via specific domains, and specific interactions/effects on cargo proteins.
FABP4 in obesity-associated carcinogenesis: Novel insights into mechanisms and therapeutic implications
Authors: Liu Shujie , Wu Dong , Fan Zhiyao , Yang Jian , Li Yongzheng , Meng Yufan , Gao Changhao , Zhan Hanxiang
Published: August 2022

The increasing prevalence of obesity worldwide is associated with an increased risk of various diseases, including multiple metabolic diseases, cardiovascular diseases, and malignant tumors. Fatty acid binding proteins (FABPs) are members of the adipokine family of multifunctional proteins that are related to fatty acid metabolism and are divided into 12 types according to their tissue origin. FABP4 is mainly secreted by adipocytes and macrophages. Under obesity, the synthesis of FABP4 increases, and the FABP4 content is higher not only in tissues but also in the blood, which promotes the occurrence and development of various cancers. Here, we comprehensively investigated obesity epidemiology and the biological mechanisms associated with the functions of FABP4 that may explain this effect. In this review, we explore the molecular mechanisms by which FABP4 promotes carcinoma development and the interaction between fat and cancer cells in obese circumstances here. This review leads us to understand how FABP4 signaling is involved in obesity-associated tumors, which could increase the potential for advancing novel therapeutic strategies and molecular targets for the systematic treatment of malignant tumors.
Exercise-induced modulation of myokine irisin in bone and cartilage tissue—Positive effects on osteoarthritis: A narrative review
Authors: Ning Ke , Wang Zhuo , Zhang Xin-an
Published: August 2022

Osteoarthritis is a chronic degenerative musculoskeletal disease characterized by pathological changes in joint structures along with the incidence of which increases with age. Exercise is recommended for all clinical treatment guidelines of osteoarthritis, but the exact molecular mechanisms are still unknown. Irisin is a newly discovered myokine released mainly by skeletal muscle in recent years—a biologically active protein capable of being released into the bloodstream as an endocrine factor, the synthesis and secretion of which is specifically induced by exercise-induced muscle contraction. Although the discovery of irisin is relatively recent, its role in affecting bone density and cartilage homeostasis has been reported. Here, we review the production and structural characteristics of irisin and discuss the effects of the different types of exercise involved in the current study on irisin and the role of irisin in anti-aging. In addition, the role of irisin in the regulation of bone mineral density, bone metabolism, and its role in chondrocyte homeostasis and metabolism is reviewed. A series of studies on irisin have provided new insights into the mechanisms of exercise training in improving bone density, resisting cartilage degeneration, and maintaining the overall environmental homeostasis of the joint. These studies further contribute to the understanding of the role of exercise in the fight against osteoarthritis and will provide an important reference and aid in the development of the field of osteoarthritis prevention and treatment.
Contraction of axonal and dendritic fields in Sox5-deficient cone bipolar cells is accompanied by axonal sprouting and dendritic hyper-innervation of pedicles
Authors: Kulesh Bridget , Reese Benjamin E. , Keeley Patrick W.
Published: August 2022

Multiple factors regulate the differentiation of neuronal morphology during development, including interactions with afferents, targets, and homotypic neighbors, as well as cell-intrinsic transcriptional regulation. Retinal bipolar cells provide an exemplary model system for studying the control of these processes, as there are 15 transcriptionally and morphologically distinct types, each extending their dendritic and axonal arbors in respective strata within the synaptic layers of the retina. Here we have examined the role of the transcription factor Sox5 in the control of the morphological differentiation of one type of cone bipolar cell (CBC), the Type 7 cell. We confirm selective expression of SOX5 in this single bipolar cell type, emerging at the close of the first post-natal week, prior to morphological differentiation. Conditional knockout mice were generated by crossing a bipolar cell-specific cre-expressing line with mice carrying floxed Sox5 alleles, as well as the Gustducin-gfp reporter which labels Type 7 CBCs. Loss of SOX5 was confirmed in the bipolar cell stratum, in GFP+ Type 7 cells. Such SOX5-deficient Type 7 cells differentiate axonal and dendritic arbors that are each reduced in areal extent. The axonal arbors exhibit sprouting in the inner plexiform layer (IPL), thereby extending their overall radial extent, while the dendritic arbors connect with fewer cone pedicles in the outer plexiform layer, showing an increase in the average number of dendritic contacts at each pedicle. SOX5-deficient Type 7 CBCs should therefore exhibit smaller receptive fields derived from fewer if now hyper-innervated pedicles, transmitting their signals across a broader depth through the IPL.
Human reaction time in a mixed reality environment
Authors: Arif Syed Muhammad Umair , Brizzi Michele , Carli Marco , Battisti Federica
Published: August 2022

Over the last few years applications based on the use of immersive environments, where physical and digital objects coexist and interact, have gained widespread attention. Thanks to the development of new visualization devices, even at low cost, and increasingly effective rendering and processing techniques, these applications are reaching a growing number of users. While the adoption of digital information makes it possible to provide immersive experiences in a number of different applications, there are still many unexplored aspects. In this work, a preliminary step to understand the impact of the scene content on human perception of the virtual 3D elements in a mixed reality has been performed. To this aim, a subjective test was designed and implemented to collect the reaction time of a set of users in a mixed reality application. In this test each user was asked to wear an augmented reality headset and to catch a virtual objects randomly appearing in the subject's field of view. We first estimated the detection accuracy through omitted, anticipated, and completed responses; then we related stimulus location, scene content and estimated accuracy. For this purpose, the area of stimulus presentation was divided into upper, lower, right, left, inner, and outer, to understand in which area responses were omitted and anticipated with respect to the central point of view. Experimental results show that, in addition to the saliency of the real scene, natural body gesture technology and limited field of view influenced human reaction time.
Computer-based assessment of unilateral spatial neglect: A systematic review
Authors: Giannakou Ioanna , Lin Dan , Punt David
Published: August 2022

Background

To date, no gold standard exists for the assessment of unilateral spatial neglect (USN), a common post-stroke cognitive impairment, with limited sensitivity provided by currently used clinical assessments. Extensive research has shown that computer-based (CB) assessment can be more sensitive, but these have not been adopted by stroke services yet.

Objective

We conducted a systematic review providing an overview of existing CB tests for USN to identify knowledge gaps and positive/negative aspects of different methods. This review also investigated the benefits and barriers of introducing CB assessment tasks to clinical settings and explored practical implications for optimizing future designs.

Methodology

We included studies that investigated the efficacy of CB neglect assessment tasks compared to conventional methods in detecting USN for adults with brain damage. Study identification was conducted through electronic database searches (e.g., Scopus), using keywords and standardized terms combinations, without date limitation (last search: 08/06/2022). Literature review and study selection were based on prespecified inclusion criteria. The quality of studies was assessed with the quality assessment of diagnostic accuracy studies tool (Quadas-2). Data synthesis included a narrative synthesis, a table summarizing the evidence, and vote counting analysis based on a direction of effect plot.

Results

A total of 28 studies met the eligibility criteria and were included in the review. According to our results, 13/28 studies explored CB versions of conventional tasks, 11/28 involved visual search tasks, and 5/28 other types of tasks. The vote counting analysis revealed that 17/28 studies found CB tasks had either equal or higher sensitivity than conventional methods and positive correlation with conventional methods (15/28 studies). Finally, 20/28 studies showed CB tasks effectively detected patients with USN within different patient groups and control groups (17/28).

Conclusions

The findings of this review provide practical implications for the implementation of CB assessment in the future, offering important information to enhance a variety of methodological issues. The study adds to our understanding of using CB tasks for USN assessment, exploring their efficacy and benefits compared to conventional methods, and considers their adoption in clinical environments.