bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Diagenesis on the Quality of Sandstone Reservoirs Exposed to High-Temperature, Overpressure, and CO2-Charging Conditions: A Case Study of Upper Miocene Huangliu Sandstones of Dongfang District, Yinggehai Basin, South China Sea
Authors: Lv Xiaowei , Fu Meiyan , Zhang Shaonan , Meng Xianghao , Liu Yi , Ding Xiaoqi , Zhang Ya , Sun Tengjiao
Published: June 2022

The Upper Miocene Huangliu sandstones of the Dongfang district are currently regarded as an important exploration target in the Yinggehai Basin. Affected by the anomalous diagenetic environments of high temperature, overpressure, and CO2 fillings, the diagenetic evolution of the Huangliu sandstones appear complicated characteristics and subsequently exert a significant influence on reservoir development. Integrated methods employed in this study include an electron microscope, cathode luminescence, X-ray diffraction, scanning electron microscope, electron microprobe, stable isotope analysis, homogenization temperature, and physical property tests. By the comparative researches between the AF-1 and AF-2 areas of the Dongfang district, the aim of this study is to investigate the complex diagenetic modifications and their controlling effects on reservoir quality and development mechanism. With similar sedimentary features, the reservoirs in the AF-1 area exhibit slightly higher porosity than those of the AF-2 area. The permeability in the AF-1 area shows one or two orders of magnitude lower than that of the AF-2 area, and throats size distribution act as a critical factor to cause distinct diversities of permeability. In the AF-1 area, the later appearance of overpressure contributed to stronger compaction intensity and more loss of primary porosity. The dissolution induced by CO2-rich thermal fluids in late stage enhanced the secondary porosity significantly and improved the total porosity. However, extensive dissolution cause abundant precipitation including carbonate cement and authigenic illite in a closed diagenetic system, which lead to the decrease of reservoirs’ permeability. As for the AF-2 area, earlier occurrence of overpressure restrained mechanical compaction obviously and further retarded corrosion of organic acid, which preserved high proportions of primary porosity. Due to lesser impact by CO2 filling, the AF-2 area had a poor intensity of dissolution and cementation, and the authigenic illitization was also restrained significantly, which effectively prevented heavy damage on reservoir quality, and especially for permeability. Based on the diagenetic evolution pathways, two types of porosity evolution patterns are established. The effect degree on diagenesis by high temperature, overpressure, and CO2 filling vary significantly between the AF-1 and AF-2 areas. The two areas show different pathways of diagenetic evolution, forming two development patterns and exhibiting different reservoir types.
Overpressures Induced by Compaction Disequilibrium Within Structural Compartments of Murree Formation, Eastern Potwar, Pakistan
Authors: Amjad Muhammad Raiees , Zafar Muhammad , Ahmad Tausif , Hussain Muyyassar , Shakir Urooj
Published: June 2022

Overpressure conditions in Potwar Basin of Pakistan pose significant drilling and completion problems. Specifically, in eastern Potwar, abnormally high pressures are observed within structural compartments of Murree Formation of Neogene age. Compaction disequilibrium and tectonic stresses are considered as two major factors, controlling pore pressures in this foreland basin. Undercompaction of sediments due to high sediment influx affects the porosity-depth relationship as the rock deviates from the normal compaction trend. Demarcation of structural geometries is critical in understanding abnormal pressure conditions within thick molasse deposits of Murree Formation. Eastern Potwar is divided into three zones on the basis of structural geometries, including duplex thrust sheets, salt-cored anticlines, and triangular zones. Geohistory analysis and pore pressure prediction have been performed for determining the overpressuring mechanism. Log-based pressure prediction in different oil fields of eastern Potwar depicts anomalous pressure conditions in some of the wells. High-sedimentation rate during Miocene times resulted in a low porosity reduction rate due to the inability of fluid to escape out of the pores. Eaton’s method was used to predict the pore pressure, and these pressure curves were calibrated against measured pressure to validate the results. Pressures predicted in Qazian-1X well showed very good correlation with measured pressure data. Most of the wells with overpressure intervals exhibited high porosity values, showing deviation from the normal compaction trend. This pressure prediction revealed that compaction disequilibrium is the primary cause of overpressure conditions within Murree Formation, resulted in response to the rapid rate of sedimentation. The deformation mechanism and presence of different structural geometries also contributed in the development of abnormal pressures.
Struggling or Succeeding in Science and Technology Education: Elementary School Students’ Individual Differences During Inquiry- and Design-Based Learning
Authors: Slim Tessa , van Schaik Johanna E. , Dobber Marjolein , Hotze Anna C. G. , Raijmakers Maartje E. J.
Published: June 2022

The primary aim of this study was to identify how elementary school students’ individual differences are related to their learning outcomes and learning process in science and technology (S&T) education, using a mixed methods design. At the start of the study, we assessed the reading comprehension, math skills, science skills, executive functions, coherence of speech, science curiosity and attitude toward S&T of 73 fifth and sixth graders. The students then received a four-lesson inquiry- and design-based learning unit on the concept of sound. Learning outcomes were measured through a pre- and post-test regarding students’ conceptual knowledge of sound, a practical assessment of design skills and a situational interest measure. A factor score regression model (N = 62) showed significant influence from prior conceptual knowledge and the latent factor “academic abilities” (reading, math, and science skills) on post conceptual knowledge. The latent factor “affective” (curiosity and attitude toward S&T) and to a lesser extend also prior conceptual knowledge were predictive of situational interest. Learning process was measured through individual interviews and student worksheets within a subsample (N = 24). We used latent profile analysis to identify three profiles based on students’ individual differences, from which the subsample for qualitative analyses was selected. Codes and themes that emerged from the qualitative analyses revealed differences between students from the three profiles. The results of this study show how different types of students succeed or struggle within S&T education, which is essential for teachers in order to differentiate their instruction and guidance. Differentiation aimed at supporting language and the integration of science into design, while facilitating a variety of learning activities and assessments that move beyond written assignments, could help achieve the most optimal learning conditions for each student.
Insight Into Rho Kinase Isoforms in Obesity and Energy Homeostasis
Authors: Wei Lei , Shi Jianjian
Published: June 2022

Obesity and associated complications increasingly jeopardize global health and contribute to the rapidly rising prevalence of type 2 diabetes mellitus and obesity-related diseases. Developing novel methods for the prevention and treatment of excess body adipose tissue expansion can make a significant contribution to public health. Rho kinase is a Rho-associated coiled-coil-containing protein kinase (Rho kinase or ROCK). The ROCK family including ROCK1 and ROCK2 has recently emerged as a potential therapeutic target for the treatment of metabolic disorders. Up-regulated ROCK activity has been involved in the pathogenesis of all aspects of metabolic syndrome including obesity, insulin resistance, dyslipidemia and hypertension. The RhoA/ROCK-mediated actin cytoskeleton dynamics have been implicated in both white and beige adipogenesis. Studies using ROCK pan-inhibitors in animal models of obesity, diabetes, and associated complications have demonstrated beneficial outcomes. Studies via genetically modified animal models further established isoform-specific roles of ROCK in the pathogenesis of metabolic disorders including obesity. However, most reported studies have been focused on ROCK1 activity during the past decade. Due to the progress in developing ROCK2-selective inhibitors in recent years, a growing body of evidence indicates more attention should be devoted towards understanding ROCK2 isoform function in metabolism. Hence, studying individual ROCK isoforms to reveal their specific roles and principal mechanisms in white and beige adipogenesis, insulin sensitivity, energy balancing regulation, and obesity development will facilitate significant breakthroughs for systemic treatment with isoform-selective inhibitors. In this review, we give an overview of ROCK functions in the pathogenesis of obesity and insulin resistance with a particular focus on the current understanding of ROCK isoform signaling in white and beige adipogenesis, obesity and thermogenesis in adipose tissue and other major metabolic organs involved in energy homeostasis regulation.
Association Between Serum Uric Acid Level and Carotid Atherosclerosis and Metabolic Syndrome in Patients With Type 2 Diabetes Mellitus
Authors: Li Wei , Wang Yan , Ouyang Shengrong , Li Mengdi , Liu Rui , Zhang Yuqi , Liu Xiaojun , Li Tianfang , Liu Shengyun
Published: June 2022

Background

Serum uric acid (SUA) is associated with many cardiovascular risk factors, such as metabolic syndrome (MetS) and subclinical atherosclerosis. However, the relationship of SUA with carotid atherosclerosis remains controversial. We aimed to investigate whether elevated SUA levels are associated with a high risk of carotid atherosclerosis and MetS in patients with type 2 diabetes mellitus (T2DM).

Methods

This cross-sectional study was performed with a sample of 1,947 hospitalized patients with T2DM. Carotid intima-media thickness and carotid artery plaques were measured via Doppler ultrasound.

Results

Uric acid levels were negatively associated with HbA1C, eGFR, and HDL-C (all P < 0.001) and positively associated with WBC, BMI, ACR, creatinine, total cholesterol, triglycerides, LDL-C, systolic blood pressure, and diastolic blood pressure (all P < 0.001). After adjusting for multiple potential confounders, the risks were substantially higher for MetS in the highest quartile of SUA levels (odds ratio: 2.91, 95% confidence interval: 1.54–5.51, P = 0.003 for trend) than in the lowest quartile of SUA levels. Furthermore, a significant increase was observed in the prevalence of overweight/obesity, hypertension, and dyslipidemia across the SUA quartiles independent of confounders. However, no significant association was found between SUA quartile with the presence of carotid atherosclerosis.

Conclusions

In patients with T2DM, SUA levels were closely associated with MetS and its components but not with carotid atherosclerosis.
Exocrine-Endocrine Crosstalk: The Influence of Pancreatic Cellular Communications on Organ Growth, Function and Disease
Authors: Overton Danielle L. , Mastracci Teresa L.
Published: June 2022

Diabetes mellitus, a disease that affects nearly 536.6 million people worldwide, is characterized by the death or dysfunction of insulin-producing beta cells of the pancreas. The beta cells are found within the islets of Langerhans, which are composed of multiple hormone-producing endocrine cells including the alpha (glucagon), delta (somatostatin), PP (pancreatic polypeptide), and epsilon (ghrelin) cells. There is direct evidence that physical and paracrine interactions between the cells in the islet facilitate and support beta cell function. However, communication between endocrine and exocrine cells in the pancreas may also directly impact beta cell growth and function. Herein we review literature that contributes to the view that “crosstalk” between neighboring cells within the pancreas influences beta cell growth and function and the maintenance of beta cell health.
Negative Effects on Neurogenesis, Ovariogenesis, and Fitness in Sea Turtle Hatchlings Associated to ex situ Incubation Management
Authors: Unda-Díaz Nancy M. , Phillips-Farfán Bryan V. , Nava Hector , Lopez-Toledo Leonel , Murata Chiharu , Lajud Naima , Herrera-Vargas Ma. Antonia , Arreola Camacho Claudia A. , Torner Luz , Fuentes-Farías Alma L. , Meléndez-Herrera Esperanza
Published: June 2022

Sea turtle egg relocation and hatchery incubation (hereafter termed ex situ incubation) is an effective strategy to protect clutches when in situ egg incubation is not viable. Nevertheless, it negatively affects the ontogenesis of male gonads and brain areas homologous to the mammalian hippocampus, as well as body size and fitness. Thus, it is imperative to analyze the effects of ex situ incubation on other developmental aspects and extend these observations to females. This work evaluated the effect of ex situ management on neurogenesis (cell proliferation in the dorsal and medial ventricular zones, neuronal integration in the dorsomedial and medial cortices), ovary cell proliferation, body size (mass and length) and self-righting ability. Additionally, this study examined if the incubation microenvironment is different between in situ and ex situ nests and whether it could contribute to explain the biological traits. An analysis of principal components showed differences in biological variables of hatchlings between in situ and ex situ clutches, driven by contrasting temperatures and silt composition. Each biological variable was also analyzed with linear mixed models using in situ vs. ex situ clutches, abiotic variables and their interaction. Turtles from ex situ clutches showed: (1) fewer proliferating cells in the dorsal and medial ventricular zones; (2) less mature neurons in the dorsomedial and medial cortices; (3) ovaries with a lesser number of proliferating cells; (4) lower body mass and length at emergence; and (5) slower self-righting time. Together, the results suggest that ex situ incubation in hatcheries is related to a slowing down of neurogenesis, ovariogenesis, body size and self-righting ability in hatchlings. Future studies should evaluate the effect of ex situ incubation on cognitive and reproductive performance to understand the long-term consequences of altered organogenesis. These studies should also disentangle the differential contribution of egg movement, reburial, nesting environment and parental origin to development. This information would likely result in better conservation strategies for sea turtles.
Antifungal Exposure and Resistance Development: Defining Minimal Selective Antifungal Concentrations and Testing Methodologies
Authors: Stevenson Emily M. , Gaze William H. , Gow Neil A. R. , Hart Alwyn , Schmidt Wiebke , Usher Jane , Warris Adilia , Wilkinson Helen , Murray Aimee K.
Published: June 2022

This scoping review aims to summarise the current understanding of selection for antifungal resistance (AFR) and to compare and contrast this with selection for antibacterial resistance, which has received more research attention. AFR is an emerging global threat to human health, associated with high mortality rates, absence of effective surveillance systems and with few alternative treatment options available. Clinical AFR is well documented, with additional settings increasingly being recognised to play a role in the evolution and spread of AFR. The environment, for example, harbours diverse fungal communities that are regularly exposed to antifungal micropollutants, potentially increasing AFR selection risk. The direct application of effect concentrations of azole fungicides to agricultural crops and the incomplete removal of pharmaceutical antifungals in wastewater treatment systems are of particular concern. Currently, environmental risk assessment (ERA) guidelines do not require assessment of antifungal agents in terms of their ability to drive AFR development, and there are no established experimental tools to determine antifungal selective concentrations. Without data to interpret the selective risk of antifungals, our ability to effectively inform safe environmental thresholds is severely limited. In this review, potential methods to generate antifungal selective concentration data are proposed, informed by approaches used to determine antibacterial minimal selective concentrations. Such data can be considered in the development of regulatory guidelines that aim to reduce selection for AFR.
Mitochondrial Homeostasis–Related lncRNAs are Potential Biomarkers for Predicting Prognosis and Immune Response in Lung Adenocarcinoma
Authors: Peng Bo , Lou Han , Chen Chen , Wang Lei , Li Huawei , Lu Tong , Na Ruisi , Xu Ran , Xin Tong , Yao Lingqi , Xu Henghui , Wang Kaiyu , Liu Xin , Zhang Linyou
Published: June 2022

The prognosis of the most common histological subtype of lung cancer, lung adenocarcinoma (LUAD), is relatively poor. Mitochondrial homeostasis depends to a great extent on the coordination between mitophagy and mitochondrial biogenesis, the deregulation of which causes various human diseases, including cancer. There is accumulating evidence that long noncoding RNAs (lncRNAs) are critical in predicting the prognosis and immune response in carcinoma. Therefore, it is critical to discern lncRNAs related to mitochondrial homeostasis in LUAD patients. In this study, we identified mitochondrial homeostasis–related lncRNAs (MHRlncRNAs) by coexpression analysis. In order to construct a prognostic signature composed of three MHRlncRNAs, univariate and multivariate Cox regression analyses were performed. Kaplan–Meier analysis, stratification analysis, principal component analysis (PCA), receiver operating characteristic (ROC) curve, gene set enrichment analysis (GSEA), and nomogram were applied to evaluate and optimize the risk model. Subsequently, we identified the mitochondrial homeostasis–related lncRNA signature (MHLncSig) as an independent predictive factor of prognosis. Based on the LUAD subtypes regrouped by this risk model, we further investigated the underlying tumor microenvironment, tumor mutation burden, and immune landscape behind different risk groups. Likewise, individualized immunotherapeutic strategies and candidate compounds were screened to aim at different risk subtypes of LUAD patients. Finally, we validated the expression trends of lncRNAs included in the risk model using quantitative real-time polymerase chain reaction (qRT-PCR) assays. The established MHLncSig may be a promising tool for predicting the prognosis and guiding individualized treatment in LUAD.
Construction of a Six-Gene Prognostic Risk Model Related to Hypoxia and Angiogenesis for Cervical Cancer
Authors: Liu Lili , Zhu Hongcang , Wang Pei , Wu Suzhen
Published: June 2022

Background: The prognosis of cervical cancer (CC) is poor and not accurately reflected by the primary tumor node metastasis staging system. Our study aimed to develop a novel survival-prediction model.

Methods: Hallmarks of CC were quantified using single-sample gene set enrichment analysis and univariate Cox proportional hazards analysis. We linked gene expression, hypoxia, and angiogenesis using weighted gene co-expression network analysis (WGCNA). Univariate and multivariate Cox regression was combined with the random forest algorithm to construct a prognostic model. We further evaluated the survival predictive power of the gene signature using Kaplan-Meier analysis and receiver operating characteristic (ROC) curves.

Results: Hypoxia and angiogenesis were the leading risk factors contributing to poor overall survival (OS) of patients with CC. We identified 109 candidate genes using WGCNA and univariate Cox regression. Our established prognostic model contained six genes (MOCSI, PPP1R14A, ESM1, DES, ITGA5, and SERPINF1). Kaplan-Meier analysis indicated that high-risk patients had worse OS (hazard ratio = 4.63, p < 0.001). Our model had high predictive power according to the ROC curve. The C-index indicated that the risk score was a better predictor of survival than other clinicopathological variables. Additionally, univariate and multivariate Cox regressions indicated that the risk score was the only independent risk factor for poor OS. The risk score was also an independent predictor in the validation set (GSE52903). Bivariate survival prediction suggested that patients exhibited poor prognosis if they had high z-scores for hypoxia or angiogenesis and high risk scores.

Conclusions: We established a six-gene survival prediction model associated with hypoxia and angiogenesis. This novel model accurately predicts survival and also provides potential therapeutic targets.
Causal Effects of Circulating Cytokines on the Risk of Psoriasis Vulgaris: A Mendelian Randomization Study
Authors: Zhao Pan , Zhang Jing , Liu Biyong , Tang Yufei , Wang Lei , Wang Guifeng , Wu Huihui , Yang Chengwei , Li Xuemei , Li Bo
Published: June 2022

Background: Psoriasis vulgaris is an inflammatory skin disease. Observational studies have shown associations between circulating cytokine levels and psoriasis vulgaris. But the causal relationship between circulating cytokine and psoriasis vulgaris remains elusive.

Methods: To assess the causal effects of cytokine levels on the risk of psoriasis vulgaris and vice versa, we performed a two-sample Mendelian randomization (MR) study by using the inverse-variance weighted (IVW), weighted median, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) in genome-wide association summary statistics of 41 circulating cytokines in up to 8,293 individuals and psoriasis vulgaris in 399,883 individuals.

Results: We identified that increasing RANTES level induced an elevated risk of psoriasis vulgaris in IVW (β = 0.33, S.E. = 0.12, p = 0.006). This causal effect showed consistency across the weighted median (β = 0.35, S.E. = 0.15, p = 0.022) and MR-PRESSO method (β = 0.33, S.E. = 0.11, p = 0.028).

Conclusions: Our results suggest a potential causal effect of elevated RANTES concentration on the increased risk of psoriasis vulgaris.
Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota
Authors: Lin Qiong-xi , Huang Wan-wen , Shen Wei , Deng Xiao-shi , Tang Zi-yu , Chen Zhen-hui , Zhao Wei , Fan Hong-ying
Published: June 2022

Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that is characterized by increased bile acid levels in maternal serum. Studies have shown that cholestatic pregnancy can result in long-term metabolic disturbances in the offspring. However, how ICP shapes the offspring’s immunity and predisposition to inflammatory disorders at an early stage is unknown. In this study, we investigated the effect of maternal cholestasis on neonatal offspring metabolism and immune function. We compared 71 neonates with ICP mothers and 63 neonates with healthy mothers and found that the incidence of jaundice and infection was significantly higher in ICP offspring. Maternal serum total bile acid level was associated with blood cell counts in full-term ICP offspring. In animal experiments, a compensatory activation of hepatic and ileal farnesoid X receptor (FXR) and altered gut microbiota in the first week were found in ICP offspring. We also investigated lipopolysaccharide (LPS)-induced inflammatory responses in neonatal rats and found that ICP offspring were more susceptible to inflammation. To understand the correlation between congenital abnormal FXR activation and tissue immunity dysregulation, we assessed the effects of the FXR agonist GW4064 and FXR antagonist E/Z-GS in ICP offspring after LPS exposure. The expression of several pro-inflammatory cytokines significantly decreased after treatment with E/Z-GS but increased after treatment with GW4064. Treatment with the probiotic Lactobacillus rhamnosus LRX01 that inhibits FXR expression in the ileum reduced susceptibility to LPS exposure in ICP offspring. The current study indicated that cholestatic pregnancy may increase the susceptibility of the offspring to inflammation by altering bile acid metabolism and gut microbiota at an early stage. We suggest that supplementation with Lactobacillus rhamnosus LRX01, which inhibits FXR expression in the ileum, may improve intestinal immunity in ICP offspring.
Stunting Status and Exposure to Infection and Inflammation in Early Life Shape Antibacterial Immune Cell Function Among Zimbabwean Children
Authors: Mutasa Kuda , Tome Joice , Rukobo Sandra , Govha Margaret , Mushayanembwa Patience , Matimba Farai S. , Chiorera Courage K. , Majo Florence D. , Tavengwa Naume V. , Mutasa Batsirai , Chasekwa Bernard , Humphrey Jean H. , Ntozini Robert , Prendergast Andrew J. , Bourke Claire D.
Published: June 2022

Background

Children who are stunted (length-for-age Z-score<-2) are at greater risk of infectious morbidity and mortality. Previous studies suggest that stunted children have elevated inflammatory biomarkers, but no studies have characterised their capacity to respond to new infections (i.e., their immune function). We hypothesised that antibacterial immune function would differ between stunted and non-stunted children and relate to their health and environment during early life.

Methods

We enrolled a cross-sectional cohort of 113 HIV-negative children nested within a longitudinal cluster-randomised controlled trial of household-level infant and young child feeding (IYCF) and water, sanitation and hygiene (WASH) interventions in rural Zimbabwe (SHINE; Clinical trials registration: NCT01824940). Venous blood was collected at 18 months of age and cultured for 24 h without antigen or with bacterial antigens: heat-killed Salmonella typhimurium (HKST) or Escherichia coli lipopolysaccharide (LPS). TNFα, IL-6, IL-8, IL-12p70, hepcidin, soluble (s)CD163, myeloperoxidase (MPO) and IFNβ were quantified in culture supernatants by ELISA to determine antigen-specific immune function. The effect of stunting status and early-life exposures (anthropometry, inflammation at 18 months, maternal health during pregnancy, household WASH) on immune function was tested in logit and censored log-normal (tobit) regression models.

Results

Children who were stunted (n = 44) had higher proportions (86.4% vs. 65.2%; 88.6% vs. 73.4%) and concentrations of LPS-specific IL-6 (geometric mean difference (95% CI): 3.46 pg/mL (1.09, 10.80), p = 0.035) and IL-8 (3.52 pg/mL (1.20, 10.38), p = 0.022) than non-stunted children (n = 69). Bacterial antigen-specific pro-inflammatory cytokine concentrations were associated with biomarkers of child enteropathy at 18 months and biomarkers of systemic inflammation and enteropathy in their mothers during pregnancy. Children exposed to the WASH intervention (n = 33) produced higher LPS- (GMD (95% CI): 10.48 pg/mL (1.84, 60.31), p = 0.008) and HKST-specific MPO (5.10 pg/mL (1.77, 14.88), p = 0.003) than children in the no WASH group (n = 80). There was no difference in antigen-specific immune function between the IYCF (n = 55) and no IYCF groups (n = 58).

Conclusions

Antibacterial immune function among 18-month-old children in a low-income setting was shaped by their stunting status and prior exposure to maternal inflammation and household WASH. Heterogeneity in immune function due to adverse exposures in early life could plausibly contribute to infection susceptibility.
Single-Cell Sequencing Analysis and Multiple Machine Learning Methods Identified G0S2 and HPSE as Novel Biomarkers for Abdominal Aortic Aneurysm
Authors: Xiong Tao , Lv Xiao-Shuo , Wu Gu-Jie , Guo Yao-Xing , Liu Chang , Hou Fang-Xia , Wang Jun-Kui , Fu Yi-Fan , Liu Fu-Qiang
Published: June 2022

Identifying biomarkers for abdominal aortic aneurysms (AAA) is key to understanding their pathogenesis, developing novel targeted therapeutics, and possibly improving patients outcomes and risk of rupture. Here, we identified AAA biomarkers from public databases using single-cell RNA-sequencing, weighted co-expression network (WGCNA), and differential expression analyses. Additionally, we used the multiple machine learning methods to identify biomarkers that differentiated large AAA from small AAA. Biomarkers were validated using GEO datasets. CIBERSORT was used to assess immune cell infiltration into AAA tissues and investigate the relationship between biomarkers and infiltrating immune cells. Therefore, 288 differentially expressed genes (DEGs) were screened for AAA and normal samples. The identified DEGs were mostly related to inflammatory responses, lipids, and atherosclerosis. For the large and small AAA samples, 17 DEGs, mostly related to necroptosis, were screened. As biomarkers for AAA, G0/G1 switch 2 (G0S2) (Area under the curve [AUC] = 0.861, 0.875, and 0.911, in GSE57691, GSE47472, and GSE7284, respectively) and for large AAA, heparinase (HPSE) (AUC = 0.669 and 0.754, in GSE57691 and GSE98278, respectively) were identified and further verified by qRT-PCR. Immune cell infiltration analysis revealed that the AAA process may be mediated by T follicular helper (Tfh) cells and the large AAA process may also be mediated by Tfh cells, M1, and M2 macrophages. Additionally, G0S2 expression was associated with neutrophils, activated and resting mast cells, M0 and M1 macrophages, regulatory T cells (Tregs), resting dendritic cells, and resting CD4 memory T cells. Moreover, HPSE expression was associated with M0 and M1 macrophages, activated and resting mast cells, Tregs, and resting CD4 memory T cells. Additional, G0S2 may be an effective diagnostic biomarker for AAA, whereas HPSE may be used to confer risk of rupture in large AAAs. Immune cells play a role in the onset and progression of AAA, which may improve its diagnosis and treatment.
Use of Single Cell Transcriptomic Techniques to Study the Role of High-Risk Human Papillomavirus Infection in Cervical Cancer
Authors: Meng Lingzhang , Chen Shengcai , Shi Guiling , He Siyuan , Wang Zechen , Shen Jiajia , Wang Jiajia , Sooranna Suren Rao , Zhao Jingjie , Song Jian
Published: June 2022

High-risk human papillomavirus (hrHPV) infection has been associated with a higher probability of progression to cervical cancer. However, several extensive studies have reported that the presence of hrHPV can lead to a better prognosis, but the mechanism of how this occurs is unclear. In this study, microbiological analysis was used to identify HPV infection as a factor for the prognosis of patients with cervical squamous cell carcinoma (CSCC). Comparing the interactions of HPV+ and HPV- malignant cells with immune cells as well as the trajectory of malignant cells either with or without HPV, we found that most of the HPV+ cells are well differentiated while HPV- cells appear to be hypo-fractionated. Using transcriptomic and immunostaining data, we validated a set of unfavourable molecules in the HPV- CSCC cells, including KRT16, ITGB1, CXCR1, VEGFA, CRCT1 and TNFRSF10B/DR5. This study provides a basis for the development of a rational post-operative follow-up programme and the development of an appropriate treatment plan for patients with cervical cancer.
Immunological Characteristics of Alternative Splicing Profiles Related to Prognosis in Bladder Cancer
Authors: Ye Fangdie , Liang Yingchun , Cheng Zhang , Liu Yufei , Hu Jimeng , Li Weijian , Chen Xinan , Gao Jiahao , Jiang Haowen
Published: June 2022

Several studies have found that pathological imbalance of alterative splicing (AS) events is associated with cancer susceptibility. carcinogenicity. Nevertheless, the relationship between heritable variation in AS events and carcinogenicity has not been extensively explored. Here, we downloaded AS event signatures, transcriptome profiles, and matched clinical information from The Cancer Genome Atlas (TCGA) database, identified the prognostic AS-related events via conducting the univariate Cox regression algorism. Subsequently, the prognostic AS-related events were further reduced by the least absolute shrinkage and selection operator (LASSO) logistic regression model, and employed for constructing the risk model. Single-sample (ssGSEA), ESTIMATE, and the CIBERSORT algorithms were conducted to evaluate tumor microenvironment status. CCK8, cell culture scratch, transwell invasion assays and flow cytometry were conducted to confirm the reliability of the model. We found 2751 prognostic-related AS events, and constructed a risk model with seven prognostic-related AS events. Compared with high-risk score patients, the overall survival rate of the patients with low-risk score was remarkably longer. Besides, we further found that risk score was also closely related to alterations in immune cell infiltration and immunotherapeutic molecules, indicating its potential as an observation of immune infiltration and clinical response to immunotherapy. In addition, the downstream target gene (DYM) could be a promising prognostic factor for bladder cancer. Our investigation provided an indispensable reference for ulteriorly exploring the role of AS events in the tumor microenvironment and immunotherapy efficiency, and rendered personalized prognosis monitoring for bladder cancer.
Distinct Fates of Chemokine and Surrogate Molecule Gradients: Consequences for CCR7-Guided Dendritic Cell Migration
Authors: Artinger Marc , Gerken Oliver J. , Purvanov Vladimir , Legler Daniel F.
Published: June 2022

Chemokine-guided leukocyte migration is a hallmark of the immune system to cope with invading pathogens. Intruder confronted dendritic cells (DCs) induce the expression of the chemokine receptor CCR7, which enables them to sense and migrate along chemokine gradients to home to draining lymph nodes, where they launch an adaptive immune response. Chemokine-mediated DC migration is recapitulated and intensively studied in 3D matrix migration chambers. A major caveat in the field is that chemokine gradient formation and maintenance in such 3D environments is generally not assessed. Instead, fluorescent probes, mostly labelled dextran, are used as surrogate molecules, thereby neglecting important electrochemical properties of the chemokines. Here, we used site-specifically, fluorescently labelled CCL19 and CCL21 to study the establishment and shape of the chemokine gradients over time in the 3D collagen matrix. We demonstrate that CCL19 and particularly CCL21 establish stable, but short-distance spanning gradients with an exponential decay-like shape. By contrast, dextran with its neutral surface charge forms a nearly linear gradient across the entire matrix. We show that the charged C-terminal tail of CCL21, known to interact with extracellular matrix proteins, is determinant for shaping the chemokine gradient. Importantly, DCs sense differences in the shape of CCL19 and CCL21 gradients, resulting in distinct spatial migratory responses.
Advances in Immune Microenvironment and Immunotherapy of Isocitrate Dehydrogenase Mutated Glioma
Authors: Yan Dongming , Li Weicheng , Liu Qibing , Yang Kun
Published: June 2022

The tumor immune microenvironment and immunotherapy have become current important tumor research concerns. The unique immune microenvironment plays a crucial role in the malignant progression of isocitrate dehydrogenase (IDH) mutant gliomas. IDH mutations in glioma can inhibit tumor-associated immune system evasion of NK cell immune surveillance. Meanwhile, mutant IDH can inhibit classical and alternative complement pathways and directly inhibit T-cell responses by metabolizing isocitrate to D-2-Hydroxyglutaric acid (2-HG). IDH has shown clinically relevant efficacy as a potential target for immunotherapy. This article intends to summarize the research progress in the immunosuppressive microenvironment and immunotherapy of IDH-mutant glioma in recent years in an attempt to provide new ideas for the study of occurrence, progression, and treatment of IDH-mutant glioma.
Differentiation of T Helper 17 Cells May Mediate the Abnormal Humoral Immunity in IgA Nephropathy and Inflammatory Bowel Disease Based on Shared Genetic Effects
Authors: Qing Jianbo , Li Changqun , Hu Xueli , Song Wenzhu , Tirichen Hasna , Yaigoub Hasnaa , Li Yafeng
Published: June 2022

Background

IgA nephropathy (IgAN) is the most frequent glomerulonephritis in inflammatory bowel disease (IBD). However, the inter-relational mechanisms between them are still unclear. This study aimed to explore the shared gene effects and potential immune mechanisms in IgAN and IBD.

Methods

The microarray data of IgAN and IBD in the Gene Expression Omnibus (GEO) database were downloaded. The differential expression analysis was used to identify the shared differentially expressed genes (SDEGs). Besides, the shared transcription factors (TFs) and microRNAs (miRNAs) in IgAN and IBD were screened using humanTFDB, HMDD, ENCODE, JASPAR, and ChEA databases. Moreover, weighted gene co-expression network analysis (WGCNA) was used to identify the shared immune-related genes (SIRGs) related to IgAN and IBD, and R software package org.hs.eg.db (Version3.1.0) were used to identify common immune pathways in IgAN and IBD.

Results

In this study, 64 SDEGs and 28 SIRGs were identified, and the area under the receiver operating characteristic curve (ROC) of 64 SDEGs was calculated and two genes (MVP, PDXK) with high area under the curve (AUC) in both IgAN and IBD were screened out as potential diagnostic biomarkers. We then screened 3 shared TFs (SRY, MEF2D and SREBF1) and 3 miRNAs (hsa-miR-146, hsa-miR-21 and hsa-miR-320), and further found that the immune pathways of 64SDEGs, 28SIRGs and 3miRNAs were mainly including B cell receptor signaling pathway, FcγR-mediated phagocytosis, IL-17 signaling pathway, toll-like receptor signaling pathway, TNF signaling pathway, TRP channels, T cell receptor signaling pathway, Th17 cell differentiation, and cytokine-cytokine receptor interaction.

Conclusion

Our work revealed the differentiation of Th17 cells may mediate the abnormal humoral immunity in IgAN and IBD patients and identified novel gene candidates that could be used as biomarkers or potential therapeutic targets.
Metastasis Related Epithelial-Mesenchymal Transition Signature Predicts Prognosis and Response to Immunotherapy in Gastric Cancer
Authors: Song Junquan , Wei Rongyuan , Huo Shiying , Gao Jianpeng , Liu Xiaowen
Published: June 2022

Background

Increasing evidence has revealed the effect of epithelial-mesenchymal transition (EMT) on tumor microenvironment and cancer treatment. However, an EMT-based signature to predict the prognosis and therapeutic effect in gastric cancer (GC) has rarely been established.

Methods

Differentially expressed genes (DEGs) between paired primary gastric and ovarian metastatic tumors were identified through comparative RNA-seq analysis, followed by the construction of metastasis-related EMT signature (MEMTS) based on DEGs and EMT gene set. Then, both The Cancer Genome Atlas (TCGA) cohort and the Asian Cancer Research Group (ACRG) cohort were analyzed to explore the potential association between MEMTS and prognosis in GC. Samsung Medical Center (SMC) cohort and two individual immunotherapy treatment cohorts, including Kim cohort and Hugo cohort, were utilized to evaluate the predictive value of MEMTS on the response to adjuvant therapy and immunotherapy, respectively. Finally, the potential association of MEMTS with tumor environment and immune escape mechanisms was investigated.

Results

High MEMTS predicted a poor prognosis in patients with GC. Patients with low MEMTS potentially gained more benefits from adjuvant chemoradiotherapy than those with high MEMTS. MEMTS reliably predicted the response to immunotherapy in GC (area under the curve = 0.896). MEMTS was significantly associated with cancer-associated fibroblasts and stromal score in the aspect of the tumor microenvironment.

Conclusion

MEMTS serves as a potential biomarker to predict the prognosis and response to adjuvant therapy and immunotherapy in GC. MEMTS-based evaluation of individual tumors enables personalized treatment for GC patients in the future.
UV-B Protective and Antioxidant Activities of Protein Hydrolysate From Sea Cucumber (Holothuria scabra) Using Enzymatic Hydrolysis
Authors: Doungapai Chitpon , Siriwoharn Thanyaporn , Malila Yuwares , Autsavapromporn Narongchai , Makkhun Sakunkhun , Yarnpakdee Suthasinee , Jantanasakulwong Kittisak , Regenstein Joe M. , Wangtueai Sutee
Published: June 2022

Sea cucumber is rich in protein that can be used to prepare a potential derived bioactive peptide for antioxidant and protective effect against UV-B induced skin cell damage. This study aimed to optimize preparation of sea cucumber hydrolysate with both UV-B protective and antioxidant activities using three commercial enzymes using response surface methodology (RSM) with a face-centered central composite design (face- centered CCD). Hydrolysis time and concentration of enzyme effects on the degree of hydrolysis (DH), yield, antioxidant and UV-B protective activities of sea cucumber hydrolysates were determined. The optimum conditions for sea cucumber hydrolysis using papain (SCP), alcalase (SCA), or flavourzyme (SCF) were 3.6, 5.0, and 4.1% (w/w protein), respectively, and a hydrolysis time of 360 min. The resulting hydrolysates had a DH of 81-91%, yield of 13-14%, IC50 for DPPH radical scavenging activity of 0.3-4.1 mg/mL, FRAP of 0.5-0.6 mmol FeSO4/mL, and IC50 for ABTS radical scavenging activity of 1.3-1.6 mg/mL. The UV-B protective activity was reported as the HaCaT cell viability percentage after UV-B treatment. The SCP, SCA, and SCF hydrolysates showed 72.4, 74.5, and 71.3% cell viability, respectively. The concentration of hydrolysates with 80% survival of HaCaT cells was 0.21, 0.15 and 0.20 mg/mL for SCP, SCA and SCF, respectively. Thus, the SCP was selected for bioactive peptide isolation and characterization. The SCP contained hydrophilic and hydrophobic amino acids of 42.4 and 57.6%, respectively. The ultrafiltration and Sephadex G-25 gel filtration chromatography were done for peptide isolation from the SCP. Six potential peptides were identified using LC-MS/MS as Leu-Val-Asn-Glu-Leu-Thr-Glu-Phe-Ala-Gln (1163 Da), Leu-Val-Asn-Glu-Val-Thr-Glu-Phe-Ala-Gln (1149 Da), Phe-Val-Asp-Ser-Ser-Ala-Thr-Thr (826 Da), Phe-Asn-Asp-Leu-Gly-Ala-Trp (821 Da), Phe-Pro-Asp-Thr-Thr-Thr-Leu (793 Da), and Lys-Phe-Gly-Glu-Gly-Lys (664).
Metabolomic Analysis Uncovers Lipid and Amino Acid Metabolism Disturbance During the Development of Ascites in Alcoholic Liver Disease
Authors: Cheng Cheng , Zhou Ming-xi , He Xian , Liu Yao , Huang Ying , Niu Ming , Liu Yi-xuan , Gao Yuan , Lu Ya-wen , Song Xin-hua , Li Hui-fang , Xiao Xiao-he , Wang Jia-bo , Ma Zhi-tao
Published: June 2022

Ascites is one of the most common complications of cirrhosis, and there is a dearth of knowledge about ascites-related pathologic metabolism. In this study, 122 alcoholic liver disease (ALD) patients, including 49 cases without ascites, 18 cases with mild-ascites, and 55 cases with large-ascites (1) were established according to the International Ascites Club (2), and untargeted metabolomics coupled with pattern recognition approaches were performed to profile and extract metabolite signatures. A total of 553 metabolites were uniquely discovered in patients with ascites, of which 136 metabolites had been annotated in the human metabolome database. Principal component analysis (PCA) analysis was used to further identify 21 ascites-related fingerprints. The eigenmetabolite calculated by reducing the dimensions of the 21 metabolites could be used to effectively identify those ALD patients with or without ascites. The eigenmetabolite showed a decreasing trend during ascites production and accumulation and was negatively related to the disease progress. These metabolic fingerprints mainly belong to the metabolites in lipid metabolism and the amino acid pathway. The results imply that lipid and amino acid metabolism disturbance may play a critical role in the development of ascites in ALD patients and could be a potent prognosis marker.
COVID-19 Vaccination Uptake Among a Nationwide Sample of People Living With HIV During the Early Phase of Vaccine Rollout in China
Authors: Yang Jianzhou , Yu Maohe , Fu Gengfeng , Lan Guanghua , Li Linghua , Qiao Ying , Zhao Jin , Qian Han-Zhu , Zhang Xiangjun , Liu Xinchao , Jin Xia , Chen Guohong , Fang Yuan , Wang Zixin , Xu Junjie
Published: June 2022

People living with HIV (PLWH), if infected with Coronavirus Disease 2019 (COVID-19), had an increased risk of mortality compared to people without HIV infection. They are considered as a priority group to receive COVID-19 vaccination. This cross-sectional online survey investigated the prevalence of and factors associated with COVID-19 vaccination uptake among 2740 PLWH aged 18–65 years in eight Chinese metropolitan cities between January and February 2021. As validated by requesting participants to send an image of receipt hiding personal identification, 6.2% of PLWH had taken up COVID-19 vaccination. Participants living in cities where individuals could make an appointment to receive COVID-19 vaccination reported significantly higher uptake than those living in cities without such allowance (11.0 vs. 2.9%, p < 0.001). Being a member of priority groups to receive vaccination, concerning about the side effects of COVID-19 vaccination and its interaction with HIV treatment, and exposing to information on the Internet/social media supporting PLWH to receive COVID-19 vaccination were significantly associated with COVID-19 vaccination uptake in both groups of participants. Receiving advice from the staff of community-based organizations supporting COVID-19 vaccination was associated with higher uptake among participants living in cities where individuals could make an appointment to receive such vaccination, while a shortage in COVID-19 vaccine supply was associated with a lower uptake among participants living in other cities. Our findings presented a snapshot of COVID-19 vaccination uptake among PLWH in the early phase of vaccine rollout in China. It provided a knowledge basis to formulate interventions promoting COVID-19 vaccination for PLWH.
Factors Associated With the Decay of Anti-SARS-CoV-2 S1 IgG Antibodies Among Recipients of an Adenoviral Vector-Based AZD1222 and a Whole-Virion Inactivated BBV152 Vaccine
Authors: Selvavinayagam Sivaprakasam T. , Yong Yean Kong , Tan Hong Yien , Zhang Ying , Subramanian Gurunathan , Rajeshkumar Manivannan , Vasudevan Kalaivani , Jayapal Priyanka , Narayanasamy Krishnasamy , Ramesh Dinesh , Palani Sampath , Larsson Marie , Shankar Esaki M. , Raju Sivadoss
Published: June 2022

Background

The magnitude of protection conferred following recovery from COVID-19 or by vaccine administration, and the duration of protective immunity developed, remains ambiguous.

Methods

We investigated the factors associated with anti-SARS-CoV-2 S1 IgG decay in 519 individuals who recovered from COVID-19 illness or received COVID-19 vaccination with two commercial vaccines, viz., an adenoviral vector-based (AZD1222) and a whole-virion-based inactivated (BBV152) vaccine in Chennai, India from March to December 2021. Blood samples collected during regular follow-up post-infection/-vaccination were examined for anti-SARS-CoV-2 S1 IgG by a commercial automated chemiluminescent immunoassay (CLIA).

Results

Age and underlying comorbidities were the two variables that were independently associated with the development of a breakthrough infection. Individuals who were >60 years of age with underlying comorbid conditions (viz., hypertension, diabetes mellitus and cardiovascular disease) had a ~15 times and ~10 times greater odds for developing a breakthrough infection and hospitalization, respectively. The time elapsed since the first booster dose was associated with attrition in anti-SARS-CoV-2 IgG, where each month passed was associated with an ebb in the anti-SARS-CoV-2 IgG antibody levels by a coefficient of −6 units.

Conclusions

Our findings advocate that the elderly with underlying comorbidities be administered with appropriate number of booster doses with AZD1222 and BBV152 against COVID-19.