bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary School Teachers’ Perceptions of the Level of Development of Low-Order Cognitive Skills Under the Content and Language Integrated Learning Approach
Authors: Campillo-Ferrer José-María , Miralles-Martínez Pedro
Published: February 2022

Content and Language Integrated Learning (CLIL) has become widespread in many countries around the world in an effort to improve learners’ communicative competence in a foreign language (FL) and content acquisition in non-language areas (NLA). A successful CLIL programme must integrate the 4Cs, i.e., content, communication, cognition and culture. In this study, we focus on the synergies of developing thinking skills by combining language, content and cognition. Specifically, the aim of this study is to examine CLIL teachers’ development of low-order cognitive skills (LOTS) in the subjects of Science and Social Science in the first two years of primary education in the Region of Murcia, Spain. For this purpose, we use a mixed method that combines qualitative and quantitative techniques to test the extent to which LOTS are developed within this integrated approach. The results show that most of the cognitive processes promoted by CLIL teachers are those related to fostering understanding among pupils, which sheds light on the strengths and weaknesses of these programmes and on a wide range of related factors on which further reviews are needed.
Does Instructional Quality Impact Male and Female University Students Differently? Focusing on Academic Stress, Academic Satisfaction, and Mental Health Impairment
Authors: Rubach Charlott , von Keyserlingk Luise , Simpkins Sandra D. , Eccles Jacquelynne S.
Published: February 2022

Gender differences in university students’ well-being and mental health are prominent concerns in higher education. During the COVID-19 pandemic, male and female students have reported specific stressors that have impacted their well-being and mental health, including difficulty concentrating, concerns about academic performance, and classroom workload. All of these stressors could be mitigated by instructional quality in courses. This study sought to better understand the associations between instructional quality and mental health impairment, i.e., poor mental health and high psychological distress, among male and female undergraduate students during the COVID-19 pandemic. We asked whether perceived instructional quality has a protective effect on students’ mental health with regard to academic stress and academic satisfaction across genders. We used longitudinal data from an ethnically diverse sample of 209 students (68% females, 82% freshmen, 50% Asian, 32% Hispanic, 13% White, 5% other) from a public university in Southern California, United States. Data were assessed during the winter and spring quarters of the academic year 2019–2020, i.e., before and after the outbreak of the COVID-19 pandemic in the US. Associations between instructional quality and students’ mental health impairment did not differ across genders. The findings indicated that perceived instructional quality at the beginning of the spring quarter 2020 was indirectly related to male and female students’ mental health impairment at the end of this quarter. This association was mediated by academic satisfaction. This finding points to a protective effect of instructional quality on students’ mental health. However, no effect was found concerning changes to mental health. Gender differences occurred in the link between academic stress and mental health impairment. Academic stress was a stronger predictor of mental health impairment for female students compared to male students. Furthermore, for female students alone, academic stress predicted changes in mental health impairment. We discuss practical implications for higher education. First, our study highlighted that instructional quality in higher education courses might lead to academic satisfaction and thereby help protect university students’ mental health. Second, higher education might consider providing additional support for (female) students to improve their stress management. We argue that improving and enhancing the academic environment are more important than reducing the burden of stressors.
Protective Effect of Maternal First-Trimester Low Body Mass Index Against Macrosomia: A 10-Year Cross-Sectional Study
Authors: Sun Yongqing , Zhang Man , Liu Ruixia , Wang Jingjing , Yang Kai , Wu Qingqing , Yue Wentao , Yin Chenghong
Published: February 2022

Objective

We aimed to assess whether maternal first-trimester low body mass index (BMI) has a protective effect against macrosomia.

Methods

This was a cross-sectional study from January 1, 2011, to June 30, 2021, and 84,900 participants were included. The predictive performance of maternal first-trimester and parental pre-pregnancy BMI for macrosomia was assessed using the area under the receiver-operating characteristics curve (AUC). Multivariate logistic regression analyses were performed to evaluate the independent effect of maternal first-trimester low BMI on macrosomia. Interactions were investigated to evaluate the potential variation of the effect of first-trimester low BMI across different groups. Furthermore, interactions were also examined across groups determined by multiple factors jointly: a) gestational diabetes mellitus (GDM)/GDM history status, parity, and maternal age; and b) GDM/GDM history status, fetal sex, and season of delivery.

Results

The proportion of macrosomia was 6.14% (5,215 of 84,900). Maternal first-trimester BMI showed the best discrimination of macrosomia (all Delong tests: P < 0.001). The protective effect of maternal first-trimester low BMI against macrosomia remained significant after adjusting for all confounders of this study [adjusted odds ratios (aOR) = 0.37, 95% CI: 0.32–0.43]. Maternal first-trimester low BMI was inversely associated with macrosomia, irrespective of parity, fetal sex, season of delivery, maternal age, and GDM/GDM history status. The protective effect was most pronounced among pregnant women without GDM/GDM history aged 25 to 29 years old, irrespective of parity (multipara: aOR = 0.32, 95% CI: 0.22–0.47; nullipara: aOR = 0.32, 95% CI: 0.24–0.43). In multipara with GDM/GDM history, the protective effect of low BMI was only observed in the 30- to 34-year-old group (aOR = 0.12, 95% CI: 0.02–0.86). For pregnant women without GDM/GDM history, the protective effect of maternal first-trimester low BMI against macrosomia was the weakest in infants born in winter, irrespective of fetal sex (female: aOR = 0.45, 95% CI: 0.29–0.69; male: aOR = 0.39, 95% CI: 0.28–0.55).

Conclusion

Maternal first-trimester low BMI was inversely associated with macrosomia, and the protective effect was most pronounced among 25- to 29-year-old pregnant women without GDM/GDM history and was only found among 30- to 34-year-old multipara with GDM/GDM history. The protective effect of maternal first-trimester low BMI against macrosomia was the weakest in winter among mothers without GDM/GDM history.
Real-Time Flash Glucose Monitoring Had Better Effects on Daily Glycemic Control Compared With Retrospective Flash Glucose Monitoring in Patients With Type 2 Diabetes on Premix Insulin Therapy
Authors: Yan Reng-na , Cai Ting-ting , Jiang Lan-lan , Jing Ting , Cai Ling , Xie Xiao-jing , Su Xiao-fei , Xu Lan , He Ke , Cheng Liang , Cheng Cheng , Liu Bing-li , Hu Yun , Ma Jian-hua
Published: February 2022

Background and Aims

To compare the effects of real-time and retrospective flash glucose monitoring (FGM) on daily glycemic control and lifestyle in patients with type 2 diabetes on premix insulin therapy.

Methods and Results

A total of 172 patients using premix insulin, with HbA1c ≥ 7.0% (56 mmol/mol), or the time below the target (TBR) ≥ 4%, or the coefficient of variation (CV) ≥36% during the screening period, were randomly assigned to retrospective FGM (n = 89) or real-time FGM group (n = 83). Another two retrospective or real-time 14-day FGMs were performed respectively, 1 month apart. Both groups received educations and medication adjustment after each FGM. Time in range (3.9~10.0 mmol/l, TIR) increased significantly after 3 months in the real-time FGM group (6.5%) compared with the retrospective FGM group (-1.1%) (p = 0.014). HbA1c decreased in both groups (both p < 0.01). Real-time FGMs increased daily exercise time compared with the retrospective group (p = 0.002).

Conclusions

Real-time FGM with visible blood glucose improves daily glycemic control and diabetes self-care behaviors better than retrospective FGM in patients with type 2 diabetes on premix insulin therapy.

Clinical Trial Registration

https://clinicaltrials.gov/NCT04847219.
The Efficacy of Nitrates for Bone Health: A Systematic Review and Meta-Analysis of Observational and Randomized Controlled Studies
Authors: Liu Weibing , Meng Zhuoran , Wang Ge
Published: February 2022

Background

Although some studies have found that nitrates were beneficial for bone health, the findings are inconsistent. To assess the efficacy of nitrates for bone health, we conducted a meta-analysis.

Methods

PubMed, EMBASE databases, Cochrane Library for relevant articles published before December 2021 were searched. All observational and randomized controlled studies that reporting bone mineral density (BMD), fractures with nitrates use were included. A meta-analysis was performed to calculate risk ratios (RRs) for fractures, change differences for bone mineral density.

Results

Four cohort studies and two case-control studies examining the association between nitrates use and fractures were identified. The nitrates use was not associated with any fracture risk (RR = 0.97; 95% CI, 0.94–1.01; I2 = 31.5%) and hip fracture (RR = 0.88; 95% CI, 0.76–1.02; I2 = 74.5%). Subgroup analyses revealed no differences in fracture risk, whereas two cohort studies revealed a reduced risk of hip fracture (RR = 0.71, 95% CI, 0.58–0.86, I2 = 0.0%). There were no statistically significant differences in BMD percent changes at lumbar spine (WMD = -0.07, 95% CI,-0.78–0.65; I2 = 0.0%), total hip (WMD = -0.42, 95% CI,-0.88–0.04; I2 = 0.0%), femoral neck (WMD = -0.38, 95% CI,-1.02–0.25; I2 = 0.0%), or total body (WMD = -0.17, 95% CI,-0.51–0.17; I2 = 0.0%) in two randomized controlled trials (RCTs) compared with a placebo. Another two RCTs compared nitrates with alendronate. Nitrates were comparable to alendronate in increasing bone mineral density at lumbar spine (WMD = 0.00, 95% CI,-0.01–0.02; I2 = 0.0%). Besides, the most common adverse effect was headache, contributing to low adherence to therapy.

Conclusion

Our meta-analysis showed no association between nitrates use and fractures in observational studies. The results of RCTs on the usage of nitrates and their effects on BMD were inconsistent. High-quality, long-term studies are needed to clarify the efficacy of nitrates for bone health.
Modeling and Energy Generation Evaluations of Large-Scale Photovoltaic Plants Equipped With Panel-Level DC Optimizers
Authors: Wang Qin , Le Lingling , Li Dahu , Ai Xiaomeng , Fang Jiakun , Yao Wei , Wen Jinyu
Published: February 2022

The distributed maximum power point tracking (DMPPT) technology, based on a DC optimizer (DCO, a DC/DC micro-converter) for each single photovoltaic (PV) panel, is one of the most popular solutions to mitigating the waste of solar energy when suffering mismatch conditions. However, the trade-off between the additional costs of deploying the panel-level power electronic equipment and the improved generation benefits of a large-scale PV plant (LPP) remains to be further studied. This study presents a static modeling method for the DCO-based distributed LPPs to study the long-term energy generation characteristics based on historical hourly weather data and then evaluate the economic benefits. The operational characteristics of the PV strings equipped with series-connected DCOs for three different topologies (Boost, Buck, and Buck-boost) are investigated, and then the control strategies for the PV-DCO generation units are proposed to maximize the energy generation of LPPs under frequent mismatch conditions. Different mismatch scenarios caused by the panel aging, geographical location settings, and the partial shading in PV arrays are simulated in the model. Six typical centralized or distributed PV plant configurations are carried out for comparison in case studies, to explore the generation characteristics and the advantages of energy production for the DCO-based distributed LPPs. Besides, the Levelized cost of energy (LCOE) which considers both the energy generation benefits and investment costs is introduced to the economic evaluation of different structures of LPPs.
Enhancing Methane Production in a Two-Stage Anaerobic Digestion of Spent Mushroom Substrate and Chicken Manure via Activation of Sludge, Optimization of Temperature, and C/N Ratio
Authors: Shu Chin-Hang , Jaiswal Rajan , Kuo Mu-do , Yu Bing-Hung
Published: February 2022

Management of spent mushroom substrate (SMS) is causing a global environmental concern due to tremendous increase in mushroom production globally. Therefore, in this research, the performance of a two-stage anaerobic co-digestion (TS-AD) of spent mushroom substrate and chicken manure was evaluated in terms of methane and biogas production and process stability with respect to single stage anaerobic digestion (SS-AD). Activation of anaerobic sludge using aeration or heat treatment in the first stage at mesophilic temperature followed by thermophilic co-digestion with chicken manure in the second stage was investigated. TS-AD exhibited better performance and enhanced methane generation over SS-AD. The optimal temperatures were determined as 35°C and 50°C for the first and the second stage of TS-AD, respectively. C/N ratio of 10 was the most suitable for biogas and methane production. TS-AD with C/N ratio of 10 and mesophilic digestion of SMS and sludge for 3 days at 35°C followed by co-digestion of the first stage effluent with chicken manure at 50°C was the optimized state producing 1359 mL of biogas of which 614.42 mL was methane, showing an increment by 59.44% in methane production as compared to SS-AD. TS-AD might be promising approach for utilization of SMS as feed stocks for biogas and methane production.
Effects of Subjective Norms and Environmental Mechanism on Green Purchase Behavior: An Extended Model of Theory of Planned Behavior
Authors: Xu Yuhuan , Du Jianguo , Khan Muhammad Aamir Shafique , Jin Shuai , Altaf Mohsin , Anwar Farooq , Sharif Imran
Published: February 2022

Based on the theory of planned behavior, this paper presents a study on the core components of attitude, subjective norm, perceived behavior control, and introduces a moral emotional variable, namely environmental indebtedness, as the emotional factors in the attitude variable to explore the influencing factors and mechanism of consumer green purchase behavior. To examine the predictors of consumer green purchase behavior, data were collected from Chinese consumers and a total of 408 responses were considered valid. Through comparative analysis, it is found that environmental cognition, descriptive norm, and self-efficacy have a highly significant positive impact on green purchase intention, and self-efficacy was found the best predictor of intention. In addition to that, when environmental indebtedness, self-efficacy, controllability, and green purchase intention jointly have significant effects on green purchase behavior, environmental indebtedness has the best effect. This research offers significant contributions and provides decision-making recommendations.
Impact of Agricultural Mechanization on Agricultural Production, Income, and Mechanism: Evidence From Hubei Province, China
Authors: Peng Jiquan , Zhao Zihao , Liu Dingning
Published: February 2022

Increasing agricultural operating income is not only an important step in improving agricultural work for farmers in the new era, but is also a powerful way to promote rural revitalization. To improve our understanding of the high-quality development of agriculture in China, the factors limiting agricultural income and the impact of the level of agricultural mechanization on agricultural production and income and its mechanism were analysed. Based on field survey data on farmers, this study analysed the influence of agricultural mechanization level on agricultural production and income by utilizing a sample-modified endogenous merging model and a threshold effect model. The level of mechanization has a significant positive impact on the cost, output value, income and return rate of all types of crops. For every 1% increase in the level of mechanization, the yields of all crops, grain crops and cash crops increase by 1.2151, 1.5941 and 0.4351%, respectively. Heterogeneity analysis shows that the level of mechanization has a certain threshold effect on income, with a greater effect occurring after the threshold. A test of action mechanism shows that the mechanization level can increase income via a factor intensification path and quality improvement path, with the partial mediation effects of the two paths being 28.8 and 27.4%, respectively. It is recommended to increase subsidies to purchase agricultural machinery, research and promote machinery suitable for cash crops, increase the level of socialized agricultural services, and improve the ability of farmers to apply novel agricultural machinery and tools so as to increase their operating profits.
The Impact of the Grain for Green Program on Farmers’ Well-Being and Its Mechanism—Empirical Analysis Based on CLDS Data
Authors: You Zhe , Wu Tong , Gong Mengqi , Zhen Shiqi , Cheng Jinhua
Published: February 2022

This paper found the optimization direction of ecological compensation project from the perspective of farmers’ well-being. Based on the data of 2016 China Labor Force Dynamic Survey (CLDS2016), this paper uses the ordered Probit model to investigate the impact of the Grain for Green Program on farmers’ subjective well-being. The study found that the Grain for Green Program significantly reduced farmers’ subjective well-being. Further research found that the Grain for Green Program ultimately inhibited the subjective well-being of farmers by reducing the subjective perception of air, soil and noise pollution, intensifying the subjective perception of water pollution and reducing the per capita income of households. In the new round of the Grain for Green Program in the “14th Five-Year Plan” period, it is advisable to increase the intensity of income compensation, strengthen supervision to ensure the payment of compensation to households, and control the scale of the project based on ecological foundation, so as to improve the well-being of farmers.
Assessing the Diversity and Distribution Pattern of the Speciose Genus Lycocerus (Coleoptera: Cantharidae) by the Global-Scale Data
Authors: Liu Tong , Liu Haoyu , Wang Younan , Xi Huacong , Yang Yuxia
Published: February 2022

Species richness patterns and endemism on the large-scale play a significant role in biogeography and biodiversity conservation. This study aimed to explore the diversity centers and endemic areas of a large cantharid genus Lycocerus, so as to test whether the hypothesis of montane and island systems biodiversity in previous studies was supported. In this study, a comprehensive species’ geographical database on the global scale consisting of 4,227 records for 324 Lycocerus species was compiled and analyzed. Species richness pattern was mapped into a grid-based map with a spatial resolution of 1° × 1° fishnet. An unbalanced pattern was identified, and it showed that the centers of species richness of Lycocerus were situated in Eastern Himalayas, Hengduan Mountains, Eastern Sichuan Mountains, Taiwan, and Japan. Further analyses based on two approaches, including parsimony analysis of endemicity (PAE) and endemicity analysis (EA), were applied to detect areas of endemism (AOEs) at three different grid sizes (1°, 1.5°, and 2°). Finally, a total of nine AOEs were detected, including five montane areas (Himalayan areas, Hengduan Mountains, South edge of China, Eastern China Mountains, and Eastern Sichuan Mountains), three islands (Taiwan Island, Japan, and Korean Peninsula), and one plateau (Shan Plateau), which were generally consistent with the species richness pattern. The results verify that montane and island systems have an essential role in promoting the formation of diversity centers and AOEs because of their complex topography, varied habitat and geological events.
Herpes simplex Virus Pneumonitis in an Acute/Subacute Paracoccidioidomycosis Patient With Malabsorption Syndrome. Case-Report and Literature Review
Authors: Cavalcante Ricardo S. , Souza Bruno S. , Duarte Iverson X. , Moraes Marcelo P. T. , Coelho Kunie I. R. , Griva Beatriz L. , Pereira Beatriz A. S. , Calvi Sueli A. , Betini Marluci , Mendes Rinaldo P.
Published: February 2022

Paracoccidioides sp.—Herpes simplex virus (HSV) co-infection was not reported until now and malabsorption syndrome is a rare complication of the acute/subacute form (AF) of paracoccidioidomycosis (PCM), characterized by life-threatening abnormalities, such as fat and protein loss, lymphopenia, ascites, and intense immunosuppression. A 21-year-old woman presented the PCM AF with intense involvement of the abdominal and intestinal lymphoid organs, which leads to the malabsorption syndrome and severe immunosuppression. This patient developed a fatal-disseminated HSV infection associated with the paracoccidioidal disease. This case demonstrates that, in addition to the antigen-specific immunosuppression, some PCM patients can present a generalized cell-mediated immune depression and endogenous infection of latent microorganisms. On the best of our knowledge, this is the first report of an association between PCM and HSV infection.
Integrated Analysis of the CircRNA-Based ceRNA Network in Renal Fibrosis Induced by Ischemia Reperfusion Injury
Authors: Wei Lei , Yu Zhixiang , Liu Limin , Zhou Ying , Bai Xiao , Wang Liya , Bai Ming , Sun Shiren
Published: February 2022

Background: Circular RNAs (circRNAs), which have broad posttranscriptional regulatory potencies, are involved in the pathogenesis of fibrotic diseases and are promising diagnostic biomarkers and therapeutic targets. However, their specific roles in renal fibrosis remain elusive.

Methods: A robust unilateral renal ischemia reperfusion injury (UIRI) mouse model was established to recapitulate the pathophysiology of renal fibrosis. The expression of circRNAs, miRNAs, and mRNAs was profiled by high-throughput RNA sequencing technology.

Results: In total, 4983 circRNAs, 216 miRNAs, and 6371 mRNAs were differentially expressed in UIRI-induced fibrotic kidneys. Candidate circRNAs and miRNAs were validated by RT–qPCR in both UIRI and unilateral ureteral obstruction mouse models. Bioinformatic analysis indicated that the parental genes of the differentially expressed circRNAs were predominantly implicated in focal adhesion, adhesion junctions, and regulation of actin cytoskeleton pathways. Through circRNA-miRNA-mRNA construction, we identified two hub genes, circSlc8a1 and circApoe, that targeted a large number of differentially expressed miRNAs and mRNAs related to metabolism and cytokine–cytokine receptor pathways, respectively.

Conclusion: CircRNAs were dysregulated in the UIRI model and might be potentially involved in the pathogenesis of renal fibrosis. Research efforts should focus on unravelling the functions of aberrantly expressed circRNAs in renal fibrosis to uncover biomarkers that would enable early diagnosis and the design of prompt therapeutic interventions to prevent disease progression.
Transcript and Protein Profiling Provides Insights Into the Molecular Mechanisms of Harvesting-Induced Latex Production in Rubber Tree
Authors: Fan Yujie , Qi Jiyan , Xiao Xiaohu , Li Heping , Lan Jixian , Huang Yacheng , Yang Jianghua , Zhang Yi , Zhang Shengmin , Tao Jun , Tang Chaorong
Published: February 2022

Natural rubber, an important industrial raw material with wide applications, is harvested in the form of latex (cytoplasm of rubber-producing laticifers) from Hevea brasiliensis (para rubber tree) by the way of tapping. Conspicuous stimulation on latex production is observed for the first few tappings conducted on virgin (untapped before) or resting (tapped before but no tapping for a period) rubber trees. To understand the underlying mechanisms, an integrative analysis of the latex transcriptome and proteome was conducted on virgin or resting Hevea trees for the first five tappings. A total of 505 non-redundant differentially expressed (DE) transcript-derived fragments (TDFs) were identified by silver-staining cDNA-AFLP, with 217 exhibiting patterns of upregulated, 180 downregulated and 108 irregularly-regulated. Meanwhile, 117 two dimensional gel electrophoresis DE-protein spots were isolated and subjected to mass spectrometry analysis, with 89 and 57 being successfully identified by MALDI-TOF and MALDI-TOF/TOF, respectively. About 72.5% DE-TDFs and 76.1% DE-proteins were functionally annotated and categorized. Noteworthily, most of the DE-TDFs implicated in sugar transport and metabolism as well as rubber biosynthesis were upregulated by the tapping treatment. The importance of sugar metabolism in harvesting-induced latex production was reinforced by the identification of abundant relevant DE-protein spots. About 83.8% of the randomly selected DE-TDFs were validated for expression patterns by semi-quantitative RT-PCR, and an 89.7% consistency for the 29 latex regeneration-related DE-TDFs examined by quantitative RT-PCR analysis. In brief, our results reveal extensive physiological and molecular changes in Hevea laticifers incurred by the tapping treatment, and the vast number of DE genes and proteins identified here contribute to unraveling the gene regulatory network of tapping-stimulated latex production.
Immune System Alterations and Postpartum Mental Illness: Evidence From Basic and Clinical Research
Authors: Dye Courtney , Lenz Kathryn M. , Leuner Benedetta
Published: February 2022

The postpartum period is a time associated with high rates of depression and anxiety as well as greater risk for psychosis in some women. A growing number of studies point to aberrations in immune system function as contributing to postpartum mental illness. Here we review evidence from both clinical and animal models suggesting an immune component to postpartum depression, postpartum anxiety, and postpartum psychosis. Thus far, clinical data primarily highlights changes in peripheral cytokine signaling in disease etiology, while animal models have begun to provide insight into the immune environment of the maternal brain and how central inflammation may also be contributing to postpartum mental illnesses. Further research investigating peripheral and central immune function, along with neural and endocrine interactions, will be important in successfully developing novel prevention and treatment strategies for these serious disorders that impact a large portion of new mothers.
AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome
Authors: Peeters Daphne , Pico-Knijnenburg Ingrid , Wieringa Douwe , Rad Mandana , Cuperus Roos , Ruige Madelon , Froeling Frank , Zijp Gerda W. , van der Burg Mirjam , Driessen Gertjan J. A.
Published: February 2022

Down syndrome (DS) is associated with increased susceptibility to infections, auto-immunity, immunodeficiency and haematological malignancies. The exact underlying immunological pathophysiology is still unclear. The immunophenotype and clinical characteristics of DS resemble those of Activated PI3K Delta Syndrome (APDS), in which the PI3K/AKT/mTOR pathway is overactivated. We hypothesized that T cell exhaustion and the hyperactivation of the AKT signalling pathway is also present in immune cells of children with DS. In this observational non-interventional cohort study we collected blood samples of children with DS (n=22) and healthy age-matched controls (n=21) for flowcytometric immunophenotyping, phospho-flow AKT analysis and exhaustion analysis of T cells. The median age was 5 years (range 1-12y). Total T and NK cells were similar for both groups, but absolute values and transitional B cells, naive memory B cells and naive CD4+ and CD8+ T cells were lower in DS. pAKT and AKT were increased for CD3+ and CD4+ T cells and CD20+ B cells in children with DS. Total AKT was also increased in CD8+ T cells. Children with DS showed increased expression of inhibitory markers Programmed cell dealth-1 (PD-1), CD244 and CD160 on CD8+ T cells and increased PD-1 and CD244+ expression on CD4+ T cells, suggesting T cell exhaustion. Children with DS show increased pAKT and AKT and increased T cell exhaustion, which might contribute to their increased susceptibility to infections, auto immunity and haematological malignancies.
Idebenone Regulates Aβ and LPS-Induced Neurogliosis and Cognitive Function Through Inhibition of NLRP3 Inflammasome/IL-1β Axis Activation
Authors: Lee Hyun-ju , Park Jin-Hee , Hoe Hyang-Sook
Published: February 2022

Idebenone is an analogue of coenzyme Q10, an electron donor in the mitochondrial electron transport chain, and thus may function as an antioxidant to facilitate mitochondrial function. However, whether idebenone modulates LPS- and Aβ-mediated neuroinflammatory responses and cognitive function in vivo is unknown. The present study explored the effects of idebenone on LPS- or Aβ-mediated neuroinflammation, learning and memory and the underlying molecular mechanisms in wild-type (WT) mice and 5xFAD mice, a mouse model of Alzheimer’s disease (AD). In male and female WT mice, idebenone upregulated neuroprotective NRF2 expression, rescued LPS-induced spatial and recognition memory impairments, and reduced NLRP3 priming and subsequent neuroinflammation. Moreover, idebenone downregulated LPS-mediated neurogliosis, reactive oxygen species (ROS) levels, and mitochondrial function in BV2 microglial cells and primary astrocytes by inhibiting NLRP3 inflammasome activation. In 5xFAD mice, idebenone increased neuroprotective NRF2 expression and improved amyloid beta (Aβ)-induced cognitive dysfunction. Idebenone downregulated Aβ-mediated gliosis and proinflammatory cytokine levels in 5xFAD mice by modulating the vicious NLRP3/caspase-1/IL-1β neuroinflammation cycle. Taken together, our results suggest that idebenone targets neuroglial NLRP3 inflammasome activation and therefore may have neuroprotective effects and inhibit the pathological progression of neuroinflammation-related diseases.
Longitudinal and Comparative Measures of Serum Chitotriosidase and YKL-40 in Patients With Idiopathic Pulmonary Fibrosis
Authors: Majewski Sebastian , Szewczyk Karolina , Jerczyńska Hanna , Miłkowska-Dymanowska Joanna , Białas Adam J. , Gwadera Łukasz , Piotrowski Wojciech J.
Published: February 2022

Background

Although chitin is absent in humans, chitinases are present in healthy subjects and show dysregulated expression in a variety of diseases resulting from abnormal tissue injury and repair responses. It was shown that chitotriosidase (chitinase 1/CHIT1) and structurally-related chitinase 3-like 1 protein (CHI3L1/YKL-40) play important roles in the pathobiology of idiopathic pulmonary fibrosis (IPF), however little is known about their longitudinal serum levels and relationship to clinical measures in IPF.

Methods

The present study is the first to evaluate serial measurements of serum CHIT1 activity and YKL-40 concentrations in patients with IPF starting antifibrotic treatment and followed up for 24 months. In addition, baseline serum CHIT1 and YKL-40 were compared between patients with IPF and control subjects, and possible CHIT1 and YKL-40 relationships to longitudinal clinical assessments in IPF were explored.

Results

Baseline serum CHIT1 activity and YKL-40 concentrations were significantly elevated in patients with IPF compared to control subjects and showed similar discriminatory ability in distinguishing IPF from controls. No significant differences between the median serum CHIT1 activity and YKL-40 concentration measured over a study follow-up were noted. We found significantly elevated baseline serum CHIT1 activity in the progressors compared with the stables in the first year, while significantly increased baseline serum CHIT1 activity was noted in the stables compared to the progressors in the second year. Additionally, we observed a significant negative correlation between a change in serum YKL-40 concentration and a change in forced vital capacity (FVC) % predicted (% pred.) in the stables subgroup, whereas, a change in serum CHIT1 activity correlated negatively with a change in FVC% pred. in the progressors subgroup.

Conclusions

This explorative study findings add further evidence that CHIT1 and YKL-40 are upregulated in patients with IPF, and suggest that longitudinally stable serum CHIT1 activity and YKL-40 concentration levels may potentially be associated with the antifibrotic treatment response. In addition, our findings are supporting the possible role of CHIT1 and YKL-40 as candidate diagnostic and prognostic biomarkers in IPF. Further research is needed to validate present study findings.
Emerging Roles of Long Non-Coding RNAs in Ankylosing Spondylitis
Authors: Sun Ruifu , Wang Xuesong , Sun Xiaohong , Zhao Bing , Zhang Xiugong , Gong Xiaojin , Wong Sunny Hei , Chan Matthew Tak Vai , Wu William Ka Kei
Published: February 2022

Ankylosing spondylitis (AS) is a chronic systemic autoimmune disease characterized by inflammation, bone erosion, spur formation of the spine and the sacroiliac joints. However, the etiology and molecular pathogenesis of AS remain largely unclear. Recently, a growing number of studies showed that long non-coding RNAs (lncRNAs) played critical roles in the development and progression of autoimmune and orthopedic conditions, including AS. Studies demonstrated that a myriad of lncRNAs (e.g. H19, MEG3, LOC645166) pertinent to regulation of inflammatory signals were deregulated in AS. A number of lncRNAs might also serve as new biomarkers for the diagnosis and predicting the outcomes of AS. In this review, we summarize lncRNA profiling studies on AS and the functional roles and mechanism of key lncRNAs relevant to AS pathogenesis. We also discuss their potential values as biomarkers and druggable targets for this potentially disabling condition.
Intravenous Immunoglobulin Therapy Restores the Quantity and Phenotype of Circulating Dendritic Cells and CD4+ T Cells in Children With Acute Kawasaki Disease
Authors: Wang Nana , Chen Zhongyue , Zhang Fan , Zhang Qianwen , Sun Ling , Lv Haitao , Wang Bo , Shen Jie , Zhou Xufang , Chen Feiyan , Zhang Binwei , Meng Lijun , Zhou Huiting , Bai ZhenJiang , Huang Jie
Published: February 2022

Background

Intravenous immunoglobulin (IVIG) showed its therapeutic efficacy on Kawasaki disease (KD). However, the mechanisms by which it reduces systemic inflammation are not completely understood. Dendritic cells (DCs) and T cells play critical roles in the pathogenic processes of immune disorders. Assessing the quantity of DC subsets and T cells and identifying functional molecules present on these cells, which provide information about KD, in the peripheral blood may provide new insights into the mechanisms of immunoglobulin therapy.

Methods

In total, 54 patients with KD and 27 age-matched healthy controls (HCs) were included in this study. The number, percentage, and phenotype of DC subsets and CD4+ T cells in peripheral blood were analyzed through flow cytometry.

Results

Patients with KD exhibited fewer peripheral DC subsets and CD4+ T cells than HCs. Human leucocyte antigen-DR (HLA-DR) expression was reduced on CD1c+ myeloid DCs (CD1c+ mDCs), whereas that on plasmacytoid DCs (pDCs) did not change significantly. Both pDCs and CD1c+ mDCs displayed significantly reduced expression of co-stimulatory molecules, including CD40, CD86. pDCs and CD1c+ mDCs presented an immature or tolerant phenotype in acute stages of KD. Number of circulating pDC and CD1c+ mDC significantly inversely correlated with plasma interleukin-6 (IL-6) levels in KD patients pre-IVIG treatment. No significant differences were found concerning the DC subsets and CD4+ T cells in patients with KD with and without coronary artery lesions. Importantly, these altered quantity and phenotypes on DC subsets and CD4+ T cells were restored to a great extent post-IVIG treatment. T helper (Th) subsets including Th1 and Th2 among CD4+ T cells did not show alteration pre- and post-IVIG treatment, although the Th1-related cytokine IFN-γ level in plasma increased dramatically in patients with KD pre-IVIG treatment.

Conclusions

pDCs and CD1c+ mDCs presented an immature or tolerant phenotype in acute stages of KD, IVIG treatment restored the quantity and functional molecules of DCs and CD4+ T cells to distinct levels in vivo, indicating the involvement of DCs and CD4+ T cells in the inflammation in KD. The findings provide insights into the immunomodulatory actions of IVIG in KD.
A 4-Benzene-Indol Derivative Alleviates LPS-Induced Acute Lung Injury Through Inhibiting the NLRP3 Inflammasome
Authors: Li Junmei , Bai Yang , Tang Yiting , Wang Xiangyu , Cavagnaro María José , Li Ling , Li Zhaozheng , Zhang Yi , Shi Jian
Published: February 2022

Acute lung injury (ALI) is a common complication of critical illness that could frequently lead to acute respiratory distress syndrome and other serious clinical consequences. Sepsis is one of the major and most common inducements among all causes of ALI. Due to its high incidence and mortality rate and also the complexity in treatment, sepsis-related ALI has become an urgent clinical problem waiting to be solved effectively. At present, only the protective ventilation strategy, restrictive fluid management, and antibiotics application are measures that can improve the prognosis with evidence-based medical proof. No pharmacological treatment is currently available to protect or significantly reverse the prognosis. Seeking for effective interventions measures for sepsis-related ALI is one of the most necessitous research directions. In this research, a conspicuous discovery of treatment-related translational use for a 4-benzene-indol derivative was elaborated by screening a large number of chemical compounds. The results showed that 4-benzene-indol derivative could not only suppress the activation of NLRP3 inflammasome both in vitro and alleviate LPS-induced ALI in vivo but also suppress the NLRP3 inflammasome in human myeloid leukemia mononuclear cells (THP-1) cell lines. Mechanistically, 1,2-diol blocks the NLRP3 inflammasome activation by disrupting NLRP3–NEK7 interaction and the subsequent NLRP3 inflammasome assembly and activation. To summarize, this research indicated that the newly-discovered 4-benzene-indol derivative targets NLRP3 inflammasome signaling, which consequently alleviates sepsis-related ALI. Collectively, the 4-benzene-indol derivative may serve as a potential therapeutic drug and NLRP3 inflammasome signaling would be a novel pharmaceutical target for clinical treatment of sepsis-related ALI.
No Significant Effects of IL-23 on Initiating and Perpetuating the Axial Spondyloarthritis: The Reasons for the Failure of IL-23 Inhibitors
Authors: Zhang Hua , Jiang Han-Lei , Dai Sheng-Ming
Published: February 2022

Axial spondyloarthritis (axSpA) is comprised of ankylosing spondylitis (AS) and non-radiographic axSpA. In recent years, the involvement of the interleukin (IL)-23/IL-17 axis in the pathophysiology of axSpA has been widely proposed. Since IL-23 is an upstream activating cytokine of IL-17, theoretically targeting IL-23 should be effective in axSpA, especially after the success of the treatment with IL-17 blockers in the disorder. Unfortunately, IL-23 blockade did not show meaningful efficacy in clinical trials of AS. In this review, we analyzed the possible causes of the failure of IL-23 blockers in AS: 1) the available data from an animal model is not able to support that IL-23 is involved in a preclinical rather than clinical phase of axSpA; 2) Th17 cells are not principal inflammatory cells in the pathogenesis of axSpA; 3) IL-17 may be produced independently of IL-23 in several immune cell types other than Th17 cells in axSpA; 4) no solid evidence supports IL-23 as a pathogenic factor to induce enthesitis and bone formation. Taken together, IL-23 is not a principal proinflammatory cytokine in the pathogenesis of axSpA.
P2Y1R Ligation Suppresses Th17 Cell Differentiation and Alleviates Colonic Inflammation in an AMPK-Dependent Manner
Authors: Chang Yao-Yao , Huan Qiu-Chan , Peng Jiao , Bi Wen-Chun , Zhai Li-Xiang , Chen Yan , Lamb Jonathan R. , Shen Xiang-Chun , Bian Zhao-Xiang , Wu Hai-qiang , Cheng Yong-Xian , Xiao Hai-Tao
Published: February 2022

P2Y1 receptor is a G-protein-coupled receptor that plays a critical role in the immune response of inflammatory bowel diseases. However, its regulatory effects on CD4+ T cell response have not been fully elucidated. The study aimed to characterize the role of P2Y1R in Th17 cell differentiation and colonic inflammation. Our results demonstrated that P2Y1R was significantly increased in the splenocytes of colitic mice, which was positively associated with the expression of RORγt and IL-17A. P2Y1R deficiency significantly ameliorated DSS-induced colitis and its Th17 responses. In parallel, P2Y1R deficiency greatly impaired the differentiation of Th17 cell, down-regulated the mRNA expression of IL-17A and RORγt, and protein expression of RORγt in vitro. More importantly, it was found that P2Y1R deficiency markedly increased AMPK phosphorylation of Th17 polarized CD4+ T cells, and antagonist of AMPK significantly reversed the inhibitory effect of P2Y1R deficiency on Th17 cell generation in vivo and in vitro. Overall, these findings demonstrated that P2Y1R deficiency could suppress Th17 cell differentiation in an AMPK-dependent manner to ameliorate colitis, and P2Y1R can act as an important regulator of Th17 cell differentiation to control colonic inflammation.
Ileal Microbiota Alters the Immunity Statues to Affect Body Weight in Muscovy Ducks
Authors: Fu Zixian , Yang Hua , Xiao Yingping , Wang Xiaoli , Yang Caimei , Lu Lizhi , Wang Wen , Lyu Wentao
Published: February 2022

The ileum is mainly responsible for food absorption and nutrients transportation. The microbes in its intestinal lumen play an essential role in the growth and health of the host. However, it is still unknown how the ileal microbes affect the body weight of the host. In this study, we used Muscovy ducks as an animal model to investigate the relationship between the ileal microbes and body weight and further explore the potential mechanism. The ileum tissue and ileal contents of 200 Muscovy ducks were collected for mRNA extraction and real-time quantitative PCR, as well as DNA separation and 16S rRNA gene sequencing. With body weight being ranked, the bottom 20% (n = 40) and top 20% (n = 40) were set as the low and high groups, respectively. Our results showed that in the ileum of Muscovy ducks, the Bacteroides, Firmicutes, and Proteobacteria were the predominant phyla with the 10 most abundant genera, namely Candidatus Arthromitus, Bacteroides, Streptococcus, Vibrio, Romboutsia, Cetobacterium, Clostridium sensu stricto 1, Terrisporobacter, Escherichia-Shigella, and Lactobacillus. We identified Streptococcus, Escherichia-Shigella, Candidatus Arthromitus, Bacteroides, Faecalibacterium, and Oscillospira were closely correlated to the growth of Muscovy ducks. Streptococcus and Escherichia-Shigella were negatively related to body weight (BW), while Candidatus Arthromitus, Bacteroides, Faecalibacterium, and Oscillospira were positively associated with BW. In addition, we found that the relative expression levels of tight junction proteins (Claudin 1, Claudin 2, ZO-1 and ZO-2) in the high group showed an upward trend, although this trend was not significant (P > 0.05). The expression of pro-inflammatory factors (IL-1β, IL-2 and TNF-α) decreased in the high group, while the anti-inflammatory factor IL-10 increased. Of course, except IL-2, these differences were not significant (P > 0.05). Finally, the correlation analysis showed that Escherichia-Shigella was significantly positively correlated with IL-1β (P < 0.05). These findings may provide fundamental data for the development of next-generation probiotics and assist the development of strategies for changing the gut microbiota to promote the growth performance in the duck industry.
Modified Mosquito Programs’ Surveillance Needs and An Image-Based Identification Tool to Address Them
Authors: Brey Jewell , Sai Sudhakar Bala Murali Manoghar , Gersch Kiley , Ford Tristan , Glancey Margaret , West Jennifer , Padmanabhan Sanket , Harris Angela F. , Goodwin Autumn
Published: February 2022

Effective mosquito surveillance and control relies on rapid and accurate identification of mosquito vectors and confounding sympatric species. As adoption of modified mosquito (MM) control techniques has increased, the value of monitoring the success of interventions has gained recognition and has pushed the field away from traditional ‘spray and pray’ approaches. Field evaluation and monitoring of MM control techniques that target specific species require massive volumes of surveillance data involving species-level identifications. However, traditional surveillance methods remain time and labor-intensive, requiring highly trained, experienced personnel. Health districts often lack the resources needed to collect essential data, and conventional entomological species identification involves a significant learning curve to produce consistent high accuracy data. These needs led us to develop MosID: a device that allows for high-accuracy mosquito species identification to enhance capability and capacity of mosquito surveillance programs. The device features high-resolution optics and enables batch image capture and species identification of mosquito specimens using computer vision. While development is ongoing, we share an update on key metrics of the MosID system. The identification algorithm, tested internally across 16 species, achieved 98.4 ± 0.6% % macro F1-score on a dataset of known species, unknown species used in training, and species reserved for testing (species, specimens respectively: 12, 1302; 12, 603; 7, 222). Preliminary user testing showed specimens were processed with MosID at a rate ranging from 181-600 specimens per hour. We also discuss other metrics within technical scope, such as mosquito sex and fluorescence detection, that may further support MM programs.
Cytochrome P450 Genes of the CYP4 Clan and Pyrethroid Resistance in Chagas Disease Vectors
Authors: Dulbecco Andrea B. , Calderón-Fernández Gustavo M. , Pedrini Nicolás
Published: February 2022

Triatomine insects are vectors of the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. Although residual pyrethroid spraying has been a successful vector control strategy for many years, a growing number of pyrethroid-resistance foci is being documented, mainly in Triatoma infestans, that led to failures in vector elimination. Insecticide resistance is a multifactorial phenomenon that often implies a combination of three different mechanisms: increased insecticide detoxification, reduced affinity of the site of action, and reduced insecticide penetration through the cuticle. All three mechanisms were reported in pyrethroid-resistant T. infestans. Cytochrome P450s are enzymes involved in the metabolism of xenobiotics and endogenous chemicals. They are encoded by CYP genes and classified into different families and clans. In triatomines, the CYP4 clan is divided in two families, CYP3093 and CYP4, and both exhibit genome-wide, triatomine-specific gene expansions. Some members from each family have been reported to be involved in two of the mechanisms mentioned above, i.e., they participate in insecticide detoxification in different organs and tissues, and in the synthesis of cuticular hydrocarbons, which ultimately can contribute to a reduced insecticide penetration. The aim of this manuscript is to review the current state of knowledge of P450 genes belonging to the CYP4 clan in triatomines and to highlight their potential role in insecticide resistance.