bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of High Jugular Bulb on the Hearing Loss Characteristics in Patients With LVAS: A Pilot Study
Authors: Kwesi Arthur Benjamin , Yu Jintao , Wang Chenlu , Wang Yonghua , Chuang Fengyi , Yan Xiaohui , Shi Wendi , Sun Yu
Published: September 2021

Objective

Both large vestibular aqueduct syndrome (LVAS) and high jugular bulb (HJB) are regarded as abnormalities commonly seen on the temporal bone CT. High jugular bulb has been found to erode the vestibular aqueduct, and there are several studies on jugular bulb vestibular aqueduct dehiscence. However, there is no study that specifically reports LVAS with concurrent HJB and its hearing loss relatedness. This study presents the pure tone audiometry differences between LVAS with HJB, and LVAS without HJB.

Methods

This was a case control study involving 36 bilateral LVAS with concurrent unilateral HJB patients, total of 72 ears. Intra-person comparison was done, by dividing ears into two groups: the case group, 36 ears (LVAS with HJB); and the control group, 36 ears (LVAS without HJB). Air conduction thresholds (250–4000 Hz), bone conduction thresholds (250–1000 Hz), and air bone gap (250–1000 Hz) were analyzed and compared between groups.

Result

There were statistically significant differences in AC thresholds at 250, 500, 2000, and 4000 Hz between the groups, p < 0.05. But there was no statistical significant difference at 1000 Hz, p > 0.05. There were statistical significant differences in BC thresholds at 250 and 500 Hz, p < 0.05, but there was no statistical difference at 1000 Hz. There were no significant differences in air bone gap at 250, 500, and 1000 Hz between the two groups.

Conclusion

LVAS with concurrent HJB was found to have higher air conduction thresholds, especially at 250, 500, 2000, and 4000 Hz. Bone conduction thresholds were higher at 250 and 500 Hz. Air bone gap at 250, 500, and 1000 Hz, were not significantly higher in LVAS with concurrent HJB.
A New Prognostic Index PDPI for the Risk of Pneumonia Among Patients With Diabetes
Authors: Guo Lingxi , Song Yanyan , Li Ni , Qin Binbin , Hu Bin , Yi Huahua , Huang Jingwen , Liu Bing , Yu Liping , Huang Yi , Zhou Min , Qu Jieming
Published: September 2021

Objective

Risk factors for the development of pneumonia among patients with diabetes mellitus are unclear. The aim of our study was to elucidate the potential risk factors and attempt to predict the probability of pneumonia based on the history of diabetes.

Methods

We performed a population-based, prospective multicenter cohort study of 1,043 adult patients with diabetes in China during 2017–2019. Demographic information, comorbidities, or laboratory examinations were collected.

Results

The study included 417 diabetic patients with pneumonia and 626 no-pneumonia-onset diabetic patients. The predictive risk factors were chosen on the basis of a multivariate logistic regression model to predict pneumonia among patients with diabetes including male sex [odds ratio (OR) = 1.72, 95% confidence interval (CI): 1.27–2.33, p < 0.001], age ≥ 75 years (OR = 2.31, 95% CI: 1.61–3.31, p < 0.001), body mass index < 25 (OR = 2.59, 95% CI: 1.92–3.50, p < 0.001), chronic obstructive pulmonary disease (OR = 6.58, 95% CI: 2.09–20.7, p = 0.001), hypertension (OR = 4.27, 95% CI: 3.12–5.85, p < 0.001), coronary heart disease (OR = 2.98, 95% CI: 1.61–5.52, p < 0.001), renal failure (OR = 1.82, 95% CI: 1.002–3.29, p = 0.049), cancer (OR = 3.57, 95% CI: 1.80–7.06, p < 0.001), use of insulin (OR = 2.28, 95% CI: 1.60–3.25, p < 0.001), and hemoglobin A1c ≥ 9% (OR = 2.70, 95% CI: 1.89–3.85, p < 0.001). A predictive nomogram was established. This model showed c-statistics of 0.811, and sensitivity and specificity were 0.717 and 0.780, respectively, under cut-off of 125 score.

Conclusion

We designed a clinically predictive tool for assessing the risk of pneumonia among adult patients with diabetes. This tool stratifies patients into relevant risk categories and may provide a basis for individually tailored intervention for the purpose of early prevention.
Yes-Associated Protein in Atherosclerosis and Related Complications: A Potential Therapeutic Target That Requires Further Exploration
Authors: Sun Congrui , He Bin , Sun Mingsheng , Lv Xiaoshuo , Wang Feng , Chen Jie , Zhang Jianbin , Ye Zhidong , Wen Jianyan , Liu Peng
Published: September 2021

Atherosclerosis and its complications diseases remain leading causes of cardiovascular morbidity and mortality, bringing a massive burden on public health worldwide. Atherosclerosis is recognized as chronic inflammation, and involves several highly correlated processes, including lipid metabolism dysfunction, endothelial cell dysfunction, inflammation, oxidative stress, vascular smooth muscle cell activation, platelet activation, thrombosis, altered matrix metabolism, and vascular remodeling. Within the past few decades, accumulating evidence has shown that the Yes-associated protein (YAP), the major effector of the Hippo pathway, can play a crucial role in pathogenesis and development of atherosclerosis. Activation of YAP-related pathways, which are induced by alerting flow pattern and matrix stiffness among others, can regulate processes including vascular endothelial cell dysfunction, monocyte infiltration, and smooth muscle cell migration, which contribute to atherosclerotic lesion formation. Further, YAP potentially modulates atherosclerotic complications such as vascular calcification and intraplaque hemorrhage, which require further investigation. Here, we summarized the relevant literature to outline current findings detailing the relationship between of YAP and atherosclerosis and highlight areas for future research.
Effects of Microbiota-Driven Therapy on Circulating Trimethylamine-N-Oxide Metabolism: A Systematic Review and Meta-Analysis
Authors: Miao Lina , Du Jianpeng , Chen Zhuhong , Shi Dazhuo , Qu Hua
Published: September 2021

Aim: This study was designed to systematically evaluate the effects of microbiota-driven therapy on decreasing TMAO and its related metabolites.

Methods and Results: PubMed, EMBASE and Cochrane Library databases were searched (up to July 2021). Randomized controlled trials (RCTs), compared microbiota-driven therapy (prebiotics, probiotics, or synbiotics) with placebo on decreasing TMAO and its related metabolites, were eligible. Two researchers extracted the data independently and the disagreement was resolved by a third researcher. The risk of bias of included study was evaluated using Cochrane tool (RoB 2.0). Meta-analysis, meta-regression analysis and publication bias analysis were performed by RevMan 5.3 or Stata 12.0 software. Ten studies (12 arms) involving 342 patients (168 patients in the intervention group and 174 patients in the control group) were included. Compared with the control group, microbiota-driven therapy did not reduce circulating TMAO [SMD = −0.05, 95% CI (−0.36, 0.26), P = 0.749], choline [SMD = −0.34, 95% CI (−1.09, 0.41), P = 0.373], betaine aldehyde [SMD = −0.704, 95% CI (−1.789, 0.382), P = 0.204], and L-carnatine [SMD = −0.06, 95% CI (−0.38, 0.25), P = 0.692].

Conclusion: Current evidence does not support that microbiota-driven treatment reduce circulating levels of TMAO, choline, betaine aldehyde, and L-carnitine. However, given the small sample size, this conclusion needs to be proved in the future.

Systematic Review Registration: PROSPERO:CRD42019119107.
Four Years of Earthquake Early Warning in Southern Iberia: 2016–2019
Authors: Carranza Marta , Mattesini Maurizio , Buforn Elisa , Zollo Aldo , Torrego Irene
Published: September 2021

The performance of an earthquake early warning system (EEWS) for southern Iberia during the period of 2016–2019 is analyzed. The software PRESTo (PRobabilistic and Evolutionary early warning SysTem; the University of Naples Federico II, Italy) operating at the Universidad Complutense de Madrid has detected 728 events (2 < Mw < 6.3), with 680 earthquakes occurring in southern Iberia. Differences between the EEWS origin time and epicenter and those of the Instituto Geográfico Nacional (IGN) catalog are less than 2 s and 20 km, respectively, for 70% of the detected earthquakes. The main differences correspond to the EEWS magnitude that is underestimated for earthquakes that occurred at the west of the Gibraltar Strait (Mw differences larger than 0.3 for 70%). To solve this problem, several relationships have been tested, and a modification to those that currently use PRESTo is proposed. Other improvements, such as to densify the network or to use 3D Earth models, are proposed to decrease the time needed to issue the alert and avoid the false alerts (19 events over a total of 728 events). The EEWS has estimated the depth for 680 events and compared to those from the IGN (491 events). The performance of PRESTo during the 2020–2021 Granada swarm is analyzed. The hypocentral locations for the three largest earthquakes are close to those from the IGN (differences from 1 to 7 km for the epicenter and 0 s for the time origin), although there are some differences in their magnitude estimations that varies from 0.2 to 0.5. The PRESTo first times are 17, 25, and 41 s after the origin time. This study shows that the actual PRESTo EEWS configured for the southern Iberia may generate effective warnings despite the low seismicity rate in this region. To decrease the warning time, the geometry and density of the seismic network must be improved together with the use of 3D Earth models and on-site system approaches.
Impact of Indian Summer Monsoon Change on Ancient Indian Civilizations During the Holocene
Authors: Laskar Amzad Hussain , Bohra Archna
Published: September 2021

A large part of South Asia receives rainfall mainly during the Indian Summer Monsoon (ISM) season of the year (Jun–Sep). The socioeconomic conditions of most of the developing countries in this region largely depend on the ISM rains. It also played important roles in rise and collapse of ancient civilizations in this region. However, the influence of the ISM on Indian ancient civilizations has not yet been fully explored though there were some attempts to correlate monsoon variation with their rise and fall. For example, in the mid to late Holocene period, Indus Valley or Harappan Civilization flourished in the western part of India from its early development, through its urbanization and eventual transformation into a rural society. Probably a prolonged decrease in the ISM rainfall caused the decline in the urban phase of the Indus Civilization around the 4.2 kyr BP global climate event. Another well-recorded early Holocene global climate event is the 8.2 kyr BP cooling event which also reportedly influenced ISM significantly, but its impact on human settlement is not clear in this region. The present study is a comprehensive review of the archaeological and climatological researches carried out on the role of ISM variability on the rise and fall of ancient Indian civilizations for the most part of the ongoing interglacial period, the Holocene. The review covers the studies on the period of the last 10 kyr as evidence suggests that human settlement and cultural developments in this region started around the beginning of this period. We have noted that the existing studies are mostly restricted to vague qualitative analysis of the weakening/strengthening of the ISM, and researches related to quantitative estimations of changes of the monsoon strengths and durations of drought events that caused collapse of civilizations are limited. Therefore, in the present analysis, emphasis has also been given on the requirement of estimating the absolute changes that might have caused cultural shifts. Some possible ways to quantitatively estimate the changes of some climate parameters are discussed.
Reflecting on the Viability of Twitter as Tool in the Postgraduate Supervision Process
Authors: Ferreira J.T.
Published: September 2021

Much has been written on the implementation of Twitter in the higher education environment, but few essays exist on the role that this social media space could potentially fulfill in the postgraduate supervision process. This role is reflected on in this paper. Key literature is reviewed that discusses the essential components of doctorateness: enculturation, communities of practice, and research identity for both student and supervisor that this role could serve. The position of this role in Africa is briefly highlighted. We postulate that Twitter may indeed serve as a valuable and meaningful platform that serves the intersection between the four components of doctorateness.
Molecular Characterization of an Aquaporin−2 Mutation Causing Nephrogenic Diabetes Insipidus
Authors: Li Qian , Lu Bichao , Yang Jia , Li Chao , Li Yanchun , Chen Hui , Li Naishi , Duan Lian , Gu Feng , Zhang Jianmin , Xia Weibo
Published: September 2021

The aquaporin 2 (AQP2) plays a critical role in water reabsorption to maintain water homeostasis. AQP2 mutation leads to nephrogenic diabetes insipidus (NDI), characterized by polyuria, polydipsia, and hypernatremia. We previously reported that a novel AQP2 mutation (G215S) caused NDI in a boy. In this study, we aimed to elucidate the cell biological consequences of this mutation on AQP2 function and clarify the molecular pathogenic mechanism for NDI in this patient. First, we analyzed AQP2 expression in Madin-Darby canine kidney (MDCK) cells by AQP2-G215S or AQP2-WT plasmid transfection and found significantly decreased AQP2-G215S expression in cytoplasmic membrane compared with AQP2-WT, independent of forskolin treatment. Further, we found co-localization of endoplasmic reticulum (ER) marker (Calnexin) with AQP2-G215S rather than AQP2-WT in MDCK cells by immunocytochemistry. The functional analysis showed that MDCK cells transfected with AQP2-G215S displayed reduced water permeability compared with AQP2-WT. Visualization of AQP2 structure implied that AQP2-G215S mutation might interrupt the folding of the sixth transmembrane α-helix and/or the packing of α-helices, resulting in the misfolding of monomer and further impaired formation of tetramer. Taken together, these findings suggested that AQP2-G215S was misfolded and retained in the ER and could not be translocated to the apical membrane to function as a water channel, which revealed the molecular pathogenic mechanism of AQP2-G215S mutation and explained for the phenotype of NDI in this patient.
GLP-1 and Underlying Beneficial Actions in Alzheimer’s Disease, Hypertension, and NASH
Authors: Li Qiu-Xuan , Gao Han , Guo Yue-Xin , Wang Bo-Ya , Hua Rong-xuan , Gao Lei , Shang Hong-Wei , Lu Xin , Xu Jing-Dong
Published: September 2021

GLP-1 is derived from intestinal L cells, which takes effect through binding to GLP-1R and is inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Since its discovery, GLP-1 has emerged as an incretin hormone for its facilitation in insulin release and reduction of insulin resistance (IR). However, GLP-1 possesses broader pharmacological effects including anti-inflammation, neuro-protection, regulating blood pressure (BP), and reducing lipotoxicity. These effects are interconnected to the physiological and pathological processes of Alzheimer’s disease (AD), hypertension, and non-alcoholic steatohepatitis (NASH). Currently, the underlying mechanism of these effects is still not fully illustrated and a better understanding of them may help identify promising therapeutic targets of AD, hypertension, and NASH. Therefore, we focus on the biological characteristics of GLP-1, render an overview of the mechanism of GLP-1 effects in diseases, and investigate the potential of GLP-1 analogues for the treatment of related diseases in this review.
Secretory Phospholipase A2s in Insulin Resistance and Metabolism
Authors: Kuefner Michael S.
Published: September 2021

The phospholipases A2 (PLA2) superfamily encompasses enzymes commonly found in mammalian tissues and snake venom. Many of these enzymes have unique tissue distribution, function, and substrate specificity suggesting distinct biological roles. In the past, much of the research on secretory PLA2s has analyzed their roles in inflammation, anti-bacterial actions, and atherosclerosis. In recent studies utilizing a variety of mouse models, pancreatic islets, and clinical trials, a role for many of these enzymes in the control of metabolism and insulin action has been revealed. In this review, this research, and the unique contributions of the PLA2 enzymes in insulin resistance and metabolism.
Burnable Poison Selection and Neutronics Analysis of Plate Fuel Assemblies
Authors: Xu Shikun , Yu Tao , Xie Jinsen , Yao Lei , Li Zhulun
Published: September 2021

Burnable poisons play a critical role in long-life pressurized water reactors. Plate fuel elements have good application prospects in long-life pressurized water reactors. In long-life pressurized water reactors with large initial residual reactivity in the core, a reasonable selection of burnable poisons can suppress the large residual reactivity at beginning of lifetime and can achieve a long burnup depth at end of lifetime. Therefore, the selection of burnable poisons is a crucial factor to be considered in the design of long-life pressurized water reactors. In this study, the selection of burnable poisons and neutronics characteristics of long-life PWR plate fuel assembly were studied. The transport-burnup calculations of different burnable poison fuel assemblies were carried out. Some candidate BPs are selected to realize the effective control of reactivity. The results show that when the enriched isotopes 157Gd, 167Er and B4C are used as burnable poisons, there is almost no reactivity penalty; when PACS-J and 231Pa are used as burnable poisons, due to their own characteristics, not only does not cause reactivity penalty at end of lifetime, but also the fuel assembly life is extended, the fuel utilization rate is improved. The combination of PACS-J and the slow-burnup burnable poisons can obtain a better reactivity curve. The results of this article show that the plate fuel assemblies can be selected with enriched isotope 157Gd, enriched isotope 167Er, B4C, 231Pa and PACS-J as burnable poisons, and the combinations of burnable poisons can be selected with two combination schemes, PACS-Er and PACS-Pa.
The Ability of Edible Fungi Residue to Remove Lead in Wastewater
Authors: Jing Yanyan , Li Zongyu , Li Yameng , Lei Gao , Li Liangliang , Yang Xin , Zhang Zhilong , Yang Wenling
Published: September 2021

Lead (Pb)-contaminated wastewater is the most common source of heavy metal ion pollution. In this study, agricultural waste edible fungi residue (EFR) was used to adsorb Pb(II) ions in wastewater as a strategy to reduce environmental pollution and minimize poisoning by Pb. The influence of Pb(II) concentration, solution pH, and EFR concentration on the removal efficiency (R) of Pb(II) was investigated with single factor design and response surface analysis. The maximum predicted R for Pb(II) was 76.34% under optimal conditions of Pb(II) concentration of 483.83 mg/L, EFR concentration of 4.99 g/L, and pH of 5.89. The actual experimental value of R reached 76.97% under these conditions. The competition of Pb(II) ions for the available adsorption sites on EFR limited the maximum R. A comparison of Fourier transform infrared spectroscopy before and after the adsorption of Pb(II), indicated that the functional groups of EFR significantly affected the effect of adsorption of heavy metals, and that the adsorption process was primarily affected by functional groups in the range of wavenumbers from 500 to 2,000 cm−1.
Comparative Transcriptomics During Brown Rot Decay in Three Fungi Reveals Strain-Specific Degradative Strategies and Responses to Wood Acetylation
Authors: Kölle Martina , Crivelente Horta Maria Augusta , Benz J. Philipp , Pilgård Annica
Published: September 2021

Brown rot fungi degrade wood in a two-step process in which enzymatic hydrolysis is preceded by an oxidative degradation phase. While a detailed understanding of the molecular processes during brown rot decay is mandatory for being able to better protect wooden products from this type of degradation, the underlying mechanisms are still not fully understood. This is particularly true for wood that has been treated to increase its resistance against rot. In the present study, the two degradation phases were separated to study the impact of wood acetylation on the behavior of three brown rot fungi commonly used in wood durability testing. Transcriptomic data from two strains of Rhodonia placenta (FPRL280 and MAD-698) and Gloeophyllum trabeum were recorded to elucidate differences between the respective decay strategies. Clear differences were found between the two decay stages in all fungi. Moreover, strategies varied not only between species but also between the two strains of the same species. The responses to wood acetylation showed that decay is generally delayed and that parts of the process are attenuated. By hierarchical clustering, we could localize several transcription factors within gene clusters that were heavily affected by acetylation, especially in G. trabeum. The results suggest that regulatory circuits evolve rapidly and are probably the major cause behind the different decay strategies as observed even between the two strains of R. placenta. Identifying key genes in these processes can help in decay detection and identification of the fungi by biomarker selection, and also be informative for other fields, such as fiber modification by biocatalysts and the generation of biochemical platform chemicals for biorefinery applications.
Female Intrasexual Competition and Its Link to Menopausal Stage, Sex Hormone Levels, and Personality Characteristics
Authors: Fiacco Serena , Arpagaus Carla , Mernone Laura , Ehlert Ulrike
Published: September 2021

Background:Female intrasexual competition (ISC) represents a unique form of social interaction. It describes behaviors primarily applied to enhance a woman's ability to outcompete other women. Previous research suggests that female ISC is influenced by personality characteristics and sex hormones. Although these factors most likely interact to predict female ISC, no previous study has investigated those factors in parallel in order to link theories from social psychology and biology. Women at the end of the reproductive lifespan represent the ideal study population, as they allow for a controlled hormonal environment.

Materials and Methods:Healthy pre- (N= 53) and postmenopausal (N= 56) women were classified according to the Stages of Reproductive Aging Workshop (STRAW+10) criteria. In the follicular phase (for premenopausal women) or on a random day (for postmenopausal women), questionnaires were administered to assess the general tendency to compete intrasexually and the tendency to compete on appearance, attention/interpersonal success, and competence. Additionally, personality characteristics (neuroticism, extraversion, openness, agreeableness, conscientiousness, and self-esteem) were assessed. On the same day, each subject provided an 8 a.m. saliva sample for estradiol, testosterone, progesterone, and dehydroepiandrosterone sulfate.T-tests tested for between-group differences and separate multiple linear regression models tested for an effect of continuous hormone levels and personality characteristics on ISC. Further models were run, testing for an interaction with menopausal stage.

Results:No group differences in ISC were evident (allp> 0.05). In premenopausal women, estradiol levels positively predicted the competition for attention (β = 2.103,p= 0.022). In postmenopausal women, self-esteem predicted the tendency to compete overall (β = −0.208,p< 0.001), on appearance (β = −0.061,p= 0.01), on competence (β = −0.087,p< 0.001), and on attention/interpersonal success (β = −0.060,p= 0.01).

Discussion:These results, though cross-sectional, suggest that women continue to compete intrasexually in postmenopause, giving rise to new questions about the function of female ISC. If confirmed, the findings will indicate that hormones guide competitiveness in fertile women, whereas self-esteem accounts for individual differences in competitiveness post-reproduction. Particularly the function of postmenopausal ISC warrants further investigation.
Paradoxical Augmentation of Experimental Spondyloarthritis by RORC Inhibition in HLA-B27 Transgenic Rats
Authors: van Tok Melissa N. , Mandour Mohamed , Wahle Joseph , Labadia Mark E. , van de Sande Marleen G. H. , Nabozny Gerald , Baeten Dominique L. , van Duivenvoorde Leonie M.
Published: September 2021

Objective

IL-17A plays a major role in the pathogenesis of spondyloarthritis (SpA). Here we assessed the impact of inhibition of RAR related orphan receptor-γ (RORC), the key transcription factor controlling IL-17 production, on experimental SpA in HLA-B27 transgenic (tg) rats.

Methods

Experimental SpA was induced by immunization of HLA-B27 tg rats with heat-inactivated Mycobacterium tuberculosis. Splenocytes obtained at day 7, 14 and 21 after immunization were restimulated ex vivo to assess the induction of pro-inflammatory cytokines. Rats were then prophylactically treated with a RORC inhibitor versus vehicle control. The biologic effect of RORC inhibition was assessed by pro-inflammatory cytokine expression in draining lymph nodes. Arthritis and spondylitis were monitored clinically, and the degree of peripheral and axial inflammation, destruction and new bone formation was confirmed by histology.

Results

Ex vivo mRNA and protein analyses revealed the rapid and selective induction of IL-17A and IL-22 production by a variety of lymphocyte subsets upon disease induction in HLA-B27 tg rats. Prophylactic RORC inhibition in vivo suppressed the expression of IL-17A, IL17F, and IL-22 without affecting the expression of other T helper cell subset related genes. This biological effect did not translate into clinical efficacy as RORC inhibition significantly accelerated the onset of arthritis and spondylitis, and aggravated the clinical severity of arthritis. This worsening of experimental SpA was confirmed by histopathological demonstration of increased inflammation, destruction, and new bone formation.

Conclusion

Despite a significant suppression of the IL-17 axis, RORC inhibitor treatment accelerates and aggravates experimental SpA in the HLA-B27 tg rat model.
Novel Insights Into the Mechanism of GVHD-Induced Tissue Damage
Authors: Ara Takahide , Hashimoto Daigo
Published: September 2021

Prophylaxis for and treatment of graft-versus-host disease (GVHD) are essential for successful allogeneic hematopoietic stem cell transplantation (allo-SCT) and mainly consist of immunosuppressants such as calcineurin inhibitors. However, profound immunosuppression can lead to tumor relapse and infectious complications, which emphasizes the necessity of developing novel management strategies for GVHD. Emerging evidence has revealed that tissue-specific mechanisms maintaining tissue homeostasis and promoting tissue tolerance to combat GVHD are damaged after allo-SCT, resulting in exacerbation and treatment refractoriness of GVHD. In the gastrointestinal tract, epithelial regeneration derived from intestinal stem cells (ISCs), a microenvironment that maintains healthy gut microbiota, and physical and chemical mucosal barrier functions against pathogens are damaged by conditioning regimens and/or GVHD. The administration of growth factors for cells that maintain intestinal homeostasis, such as interleukin-22 (IL-22) for ISCs, R-spondin 1 (R-Spo1) for ISCs and Paneth cells, and interleukin-25 (IL-25) for goblet cells, mitigates murine GVHD. In this review, we summarize recent advances in the understanding of GVHD-induced tissue damage and emerging strategies for the management of GVHD.
Preterm Birth Is Associated With Immune Dysregulation Which Persists in Infants Exposed to Histologic Chorioamnionitis
Authors: Sullivan Gemma , Galdi Paola , Borbye-Lorenzen Nis , Stoye David Q. , Lamb Gillian J. , Evans Margaret J. , Skogstrand Kristin , Chandran Siddharthan , Boardman James P.
Published: September 2021

Introduction

Preterm infants are at increased risk of exposure to histologic chorioamnionitis (HCA) when compared to term-born controls, and this is associated with several neonatal morbidities involving brain, lungs and gut. Preterm infants could benefit from immunomodulatory therapies in the perinatal period, but development of rational treatment strategies requires improved characterization of the perinatal response to HCA. We had two objectives: The first, to characterize the umbilical cord blood immune profile in preterm infants compared to term-born controls; the second, to investigate the postnatal immune response in preterm infants exposed to HCA versus those who were not.

Population

For objective one 59 term infants [mean gestational age (GA) 39+4 (37+3 to 42+0)] and 55 preterm infants [mean GA29+0(23+3 to 32+0)] with umbilical cord samples available were included; for objective two we studied 96 preterm infants [mean GA29+1(23+2 to 32+0)] for whom placental histology and postnatal blood samples were available.

Methods

Placental histopathology was used to identify reaction patterns indicative of HCA, and a customized immunoassay of 24 inflammatory markers and trophic proteins selected to reflect the perinatal immune response was performed on umbilical cord blood in term and preterm participants and postnatal day 5 blood in the preterm group.

Results

The umbilical cord blood immune profile classified gestational age category with 86% accuracy (95% CI 0.78-0.92), p-value=1.242x10-14. Pro-inflammatory proteins IL-6, MCP-1 and CRP were elevated in the cord blood of preterm infants whilst BDNF, C3, C9, IL-18, MMP-9 and RANTES were decreased, compared to infants born at term. In preterm infants, exposure to HCA was associated with elevations in 8 immune proteins on postnatal day 5 (BDNF, C3, C5a, C9, IL-8, MCP-1, MIP-1β and MMP-9) when compared to preterm infants who were not exposed.

Conclusion

Preterm birth is associated with a distinct immune profile in umbilical cord blood and preterm infants exposed to HCA with evidence of a fetal inflammatory response have specific alterations in immune function that are apparent on day 5 of postnatal life.
With Chitosan and PLGA as the Delivery Vehicle, Toxoplasma gondii Oxidoreductase-Based DNA Vaccines Decrease Parasite Burdens in Mice
Authors: Yu Zhengqing , Cao Wandi , Gao Xuchen , Aleem Muhammad Tahir , Liu Junlong , Luo Jianxun , Yan Ruofeng , Xu Lixin , Song Xiaokai , Li Xiangrui
Published: September 2021

Toxoplasma gondii (T. gondii) is an intracellular parasitic protozoan that can cause serious public health problems. However, there is no effectively preventive or therapeutic strategy available for human and animals. In the present study, we developed a DNA vaccine encoding T. gondii oxidoreductase from short-chain dehydrogenase/reductase family (TgSDRO-pVAX1) and then entrapped in chitosan and poly lactic-co-glycolic acid (PLGA) to improve the efficacy. When encapsulated in chitosan (TgSDRO-pVAX1/CS nanospheres) and PLGA (TgSDRO-pVAX1/PLGA nanospheres), adequate plasmids were loaded and released stably. Before animal immunizations, the DNA vaccine was transfected into HEK 293-T cells and examined by western blotting and laser confocal microscopy. Th1/Th2 cellular and humoral immunity was induced in immunized mice, accompanied by modulated secretion of antibodies and cytokines, promoted the maturation and MHC expression of dendritic cells, and enhanced the percentages of CD4+ and CD8+ T lymphocytes. Immunization with TgSDRO-pVAX1/CS and TgSDRO-pVAX1/PLGA nanospheres conferred significant immunity with lower parasite burden in the mice model of acute toxoplasmosis. Furthermore, our results also lent credit to the idea that TgSDRO-pVAX1/CS and TgSDRO-pVAX1/PLGA nanospheres are substitutes for each other. In general, the current study proposed that TgSDRO-pVAX1 with chitosan or PLGA as the delivery vehicle is a promising vaccine candidate against acute toxoplasmosis.
Eutrophication and Hypoxia in Tropical Negombo Lagoon, Sri Lanka
Authors: Hsieh Hsueh-Han , Chuang Ming-Hsiu , Shih Yung-Yen , Weerakkody W. Sanjaya , Huang Wei-Jen , Hung Chin-Chang , Muller François L. L. , Ranatunga R. R. M. K. P. , Wijethunga D. S.
Published: September 2021

Hypoxic events are becoming frequent in some estuaries and coastal waters due to over-enrichment of anthropogenic nutrients, organic matter, and/or due to restricted water circulation. The coastal lagoons and estuaries of Sri Lanka are facing high population pressure and lacking sufficient infrastructure. Coastal lagoons may receive high anthropogenic inputs of natural or untreated nitrogen and phosphorus wastes, and consequently result in hypoxic conditions while sluggish circulation occurred. In this study, we examined the spatiotemporal variability of eutrophication and hypoxia in the Negombo Lagoon, one of the most productive and sensitive coastal ecosystems in Sri Lanka. Based on seasonal measurements of dissolved oxygen, nutrients, chlorophyll-a (Chl-a), particulate and dissolved organic carbon (POC and DOC), we concluded that eutrophication and hypoxia occurred in both the dry and wet seasons. The main contributing factors were high seawater temperature and poor water circulation in the dry season and high nutrient loading combined with elevated POC and DOC inputs in the wet season.
An Integrated Approach to Determine the Stock Structure of Spinyhead Croaker Collichthys lucidus (Sciaenidae) in Chinese Coastal Waters
Authors: Zhang Shuai , Li Min , Zhu Jiangfeng , Xu Shannan , Chen Zuozhi
Published: September 2021

An integrated approach including analyses of different biological traits is a proven and powerful tool used to assess the population structures of fish species, which is vital for fishery stock conservation and management of wild resources. This study evaluates the use of three natural tags (i.e., microsatellites, parasites, and otolith nucleus chemistry) in order to describe the population structure of the spinyhead croaker, Collichthys lucidus, in the coastal waters of China, on evolutionary and ecological time scales. Spinyhead croaker was assigned with 86% accuracy to its regional origin (northern China vs. southern China) using all three natural tags. Accuracy decreased when incorporating only one type of natural tag (genetics: 19–69%; parasites: 30–60%; otolith chemistry: 51–86%) or when assigning the fish to a fine scale (sea areas: 44–64%; sampled estuaries: 19–66%). However, the overall accuracy assignment improved slightly compared with otolith chemistry (estuaries: 55 vs. 51%; sea areas: 66 vs. 64%; regions: 86 vs. 86%). Three natural tags and integrated results show that C. lucidus in Chinese coastal waters can be separated into distinct northern and southern Chinese stocks. Finally, this information should promote the development of effective conservation strategies and integrated fisheries management plans for this commercially important species.
A Genome-Wide Association Study Identifies Candidate Genes Associated With Shell Color in Bay Scallop Argopecten irradians irradians
Authors: Zhu Xinghai , Zhang Junhao , Hou Xiujiang , Liu Pingping , Lv Jia , Xing Qiang , Huang Xiaoting , Hu Jingjie , Bao Zhenmin
Published: September 2021

Molluscan shell color has consistently drawn attention for its abundant diversity and commercial use in shellfish breeding projects. Recently, two new strains of bay scallop (Argopecten irradians irradians) with different shell colors as marked phenotypic traits have been artificially bred to improve their economic values; however, the inheritance mechanism of their shell pigmentation is still unclear. In this study, a genome-wide association study (GWAS) was conducted to determine the genetic basis of shell color in bay scallops utilizing 29,036 high-quality single-nucleotide polymorphisms (SNPs) derived from 80 purple-red (PP) and 80 black-brown (BP) shell color individuals. The result of the GWAS showed that 469 SNPs (p <1.72E−6) significantly associated with shell color were mainly distributed in chromosome 7. The top three SNPs (i.e., chr7-12764003, chr7-13213864, and chr7-11899306) are located in the genic region of G-protein-coupled receptor-like 101 (GRL101), polyketide synthase 1 (PKS1), and phosphoinositide phospholipase C (PLC1), which have been widely reported to be involved in pigmentation. Successfully, the top three SNPs were verified in another non-breeding bay scallop population. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses obtained 38 GO terms covering 297 genes and aggregating pathways involving 252 annotated genes. Specifically, the expression profiles of the top three identified candidate genes were detected in mantles of PP and BP individuals by real-time quantitative reverse transcription PCR. The significantly higher expression levels of GRL101 (6.43-fold) and PLC1 (6.48-fold) in PP, and PKS1 (12.02-fold) in BP implied that GRL101 and PLC1 potentially functioned in PP shell coloration, and black pigmentation in BP might be principally regulated by PKS1. Our data provide valuable information for deciphering the phenotype differences of shell color in the bay scallop.
Running Behind “POPO”—Impact of Predictors of Poor Outcome for Treatment Stratification in Pediatric Crohn's Disease
Authors: de Laffolie Jan , Zimmer Klaus-Peter , Sohrabi Keywan , Hauer Almuthe Christina
Published: September 2021

Background and Aims: Intensifying therapy for Paediatric Crohn's Disease (CD) by early use of immunomodulators and biologics has been proposed for cases in which predictors of poor outcome (POPO) were present. We investigated therapy stratifying potential comparing POPO-positive and -negative CD patients from CEDATA-GPGE®, a German-Austrian Registry for Paediatric Inflammatory Bowel disease.

Methods: CD patients (1–18 years) registered in CEDATA-GPGE® (2004–2018) within 3 months of diagnosis and at least two follow-up visits were included. Disease course and treatments over time were analysed regarding positivity of POPO criteria and test statistical properties.

Results: 709/1084 patients included had at least one POPO criterion (65.4%): 177 patients (16.3%) had persistent disease (POPO2), 581 (53.6%) extensive disease (POPO3), 21 (1.9%) severe growth retardation POPO4, 47 (4.3%) stricturing/penetrating disease (POPO6) and 122 (11.3%) perianal disease (POPO7). Patients with persistent disease differed significantly in lack of sustained remission >1 year (Odd Ratio (OR) 1.49 [1.07–2.07], p = 0.02), patients with initial growth failure in growth failure at end of observation (OR 51.16 [19.89–131.62], p < 0.0001), patients with stricturing and penetrating disease as well as perianal disease in need for surgery (OR 17.76 [9.39–33.58], p < 0.001; OR 2.56 [1.58–4.15], p < 0.001, respectively). Positive Predictive Value for lack of sustained remission was >60% for patients with initial growth failure, persistent or stricturing/penetrating disease.

Conclusion: Predictors of poor outcome with complicated courses of disease were common in CEDATA-GPGE®. An early intensified approach for paediatric CD patients with POPO-positivity (POPO2-4, 6-7) should be considered, because they have an increased risk to fare poorly.
Development and Functional Characterization of Fetal Lung Organoids
Authors: Laube Mandy , Pietsch Soeren , Pannicke Thomas , Thome Ulrich H. , Fabian Claire
Published: September 2021

Preterm infants frequently suffer from pulmonary complications due to a physiological and structural lung immaturity resulting in significant morbidity and mortality. Novel in vitro and in vivo models are required to study the underlying mechanisms of late lung maturation and to facilitate the development of new therapeutic strategies. Organoids recapitulate essential aspects of structural organization and possibly organ function, and can be used to model developmental and disease processes. We aimed at generating fetal lung organoids (LOs) and to functionally characterize this in vitro model in comparison to primary lung epithelial cells and lung explants ex vivo. LOs were generated with alveolar and endothelial cells from fetal rat lung tissue, using a Matrigel-gradient and air-liquid-interface culture conditions. Immunocytochemical analysis showed that the LOs consisted of polarized epithelial cell adhesion molecule (EpCAM)-positive cells with the apical membrane compartment facing the organoid lumen. Expression of the alveolar type 2 cell marker, RT2-70, and the Club cell marker, CC-10, were observed. Na+ transporter and surfactant protein mRNA expression were detected in the LOs. First time patch clamp analyses demonstrated the presence of several ion channels with specific electrophysiological properties, comparable to vital lung slices. Furthermore, the responsiveness of LOs to glucocorticoids was demonstrated. Finally, maturation of LOs induced by mesenchymal stem cells confirmed the convenience of the model to test and establish novel therapeutic strategies. The results showed that fetal LOs replicate key biological lung functions essential for lung maturation and therefore constitute a suitable in vitro model system to study lung development and related diseases.
The CERN-MEDICIS Isotope Separator Beamline
Authors: Martinez Palenzuela Yisel , Barozier Vincent , Chevallay Eric , Cocolios Thomas E. , Duchemin Charlotte , Fernier Pascal , Huyse Mark , Lambert Laura , Lopez Roberto , Marzari Stefano , Ramos Joao P. , Stora Thierry , Van Duppen Piet , Vorozhtsov Alexey
Published: September 2021

CERN-MEDICIS is an off-line isotope separator facility for the extraction of radioisotopes from irradiated targets of interest to medical applications. The beamline, between the ion source and the collection chamber, consists of ion extraction and focusing elements, and a dipole magnet mass spectrometer recovered from the LISOL facility in Louvain-la-Neuve. The latter has been modified for compatibility with MEDICIS, including the installation of a window for injecting laser light into the ion source for resonance photo-ionization. Ion beam optics and magnetic field modeling using SIMION and OPERA respectively were performed for the design and characterization of the beamline. The individual components and their optimal configuration in terms of ion beam extraction, mass separation, and ion transport efficiency is described, along with details of the commissioning and initial performance assessment with stable ion beams.
Parasitoid Causes Cascading Effects on Plant-Induced Defenses Mediated Through the Gut Bacteria of Host Caterpillars
Authors: Wang Jie , Mason Charles J. , Ju Xueyang , Xue Rongrong , Tong Lu , Peiffer Michelle , Song Yuanyuan , Zeng Rensen , Felton Gary W.
Published: September 2021

Koinobiont endoparasitoid wasps whose larvae develop inside a host insect alter several important facets of host physiology, potentially causing cascading effects across multiple trophic levels. For instance, the hijacking of the host immune responses may have effects on how insects interact with host plants and microbial associates. However, the parasitoid regulation of insect–plant–microbiome interactions is still understudied. In this study, we used the fall armyworm (FAW), Spodoptera frugiperda, and the braconid parasitoid Cotesia marginiventris to evaluate impacts of parasitism on the gut microbiome of FAW larvae, and respective maize plant defense responses. The level of reactive oxygen species and the microbial community in larval gut underwent significant changes in response to parasitism, leading to a significant reduction of Enterococcus, while elevating the relative abundance of Pseudomonas. FAW with parasitism had lower glucose oxidase (GOX) activity in salivary glands and triggered lower defense responses in maize plants. These changes corresponded to effects on plants, as Pseudomonas inoculated larvae had lower activity of salivary GOX and triggered lower defense responses in maize plants. Our results demonstrated that parasitism had cascading effects on microbial associates across trophic levels and also highlighted that insect gut bacteria may contribute to complex interrelationships among parasitoids, herbivores, and plants.
Delivery of miR-26a Using an Exosomes-Based Nanosystem Inhibited Proliferation of Hepatocellular Carcinoma
Authors: Mahati Shaya , Fu Xiangjun , Ma Xuexian , Zhang Hua , Xiao Lei
Published: September 2021

Background: MicroRNA (abbreviated miRNA)-based treatment holds great promise for application as clinical antitumor therapy, but good carriers for delivery of the miRNA drug are lacking. Exosomes secreted by mesenchymal stem cells (MSCs) have proved to be safe, and exogenously modified exosomes may potentially represent an excellent drug delivery vehicle.

Methods: In this study, we designed a delivery nano system using single-stranded variable fragment (scFv)-modified exosomes derived from human cord blood MSCs. Genetic engineering technology was used to obtain anti-Glypican 3 (GPC3) scFv-modified exosomes, which were then loaded with miR-26a mimics through electroporation.

Results: Results of electron microscopy and dynamic light scattering indicated that the diameter of the drug-carrying exosomes was about 160 nm. Furthermore, anti-GPC3 scFv-modified exosomes effectively delivered miR-26a to GPC3-positive hepatocellular carcinoma cells, thereby inhibiting cell proliferation and migration by regulating the expression of downstream target genes of miR-26a. The exosomes-based nano system displayed favorable anti-tumor effect in vivo with no obvious side effects.

Conclusion: Our data provided a new perspective for the use of exosome delivery systems for miRNA-based antitumor therapy.
The Effect and Mechanism of Cholesterol and Vitamin B12 on Multi-Domain Cognitive Function: A Prospective Study on Chinese Middle-Aged and Older Adults
Authors: Wang Lijing , Liu Kuo , Zhang Xiaona , Wang Yushan , Liu Wen , Wang Tao , Hao Ling , Ju Mengwei , Xiao Rong
Published: September 2021

Background: Nutrients are associated with cognitive function, but limited research studies have systematically evaluated on multi-domain cognitive function. The aim of this study was to investigate the effect and mechanism of specific nutrient on multi-domain cognitive function, and provide nutrition guidance for improving cognitive function.

Methods: Participants were selected based on a multicenter prospective study on middle-aged and older adults in China. Global cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Nutrients intake was assessed according to food frequency questionnaire and China Food Composition Database, and principal component analysis was performed to extract nutrient patterns. Associations between specific nutrients and cognitive function were assessed using log-binomial regression. Restricted cubic spline was used to illustrate the dose-response relationship of nutrients with multi-domain cognitive function. Mediation analysis was used to determine the mechanism of nutrients in cognitive function.

Results: Four nutrient patterns were identified (vitamin-mineral, protein-carbohydrate, fatty acid-vitamin E, and cholesterol-vitamin B12), and only a nutrient pattern rich in cholesterol and vitamin B12 was found associated with cognitive function (RR = 0.891, 95%CI = 0.794–0.999). In multi-domain cognitive function, dietary cholesterol and vitamin B12 were related to better performance of visual memory function (P = 0.034, P = 0.02). In dose-response relationship, it suggested a U-shaped association between vitamin B12 and MMSE (P = 0.02) within a certain range.

Conclusions: Dietary intake rich in cholesterol and vitamin B12 was associated with better cognitive function, and vitamin B12 had a U-shaped dose-response relation with MMSE. Thus, ensuring moderate cholesterol and vitamin B12intake may be an advisable strategy to improve cognitive function in middle-aged and older adults.

Clinical Trial Registration: EMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610