bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Pharmacological Autophagy Regulators of Active Ulcerative Colitis
Authors: Qiu Peishan , Liu Lan , Fang Jun , Zhang Meng , Wang Haizhou , Peng Yanan , Chen Min , Liu Jing , Wang Fan , Zhao Qiu
Published: December 2021

Background: Ulcerative colitis (UC) is a chronic recurrent disease of unknown etiology. Recently, it has been reported that autophagy-related gene polymorphism is closely associated with increased risk of UC, and the therapeutic effect of some UC drugs is mediated by regulating autophagy pathways. This study aims to identify pivotal autophagy-related regulators in UC pathogenesis and provide novel molecular targets for the treatment of active UC.

Methods: Gene expression profiles and clinical information of active UC patients were obtained from GEO databases. CIBERSORT was adopted to evaluate the immune cell infiltration. We used weighted gene co-expression network analysis (WGCNA) and differential expression analysis to identify the pivotal modules and genes associated with active UC. Subsequently, we conducted validation in the validation set and explored its relationship with commonly used UC therapeutics.

Results: 36 healthy controls and 46 active UC patients have been obtained from the training set of GSE53306, GSE87466, and GSE134025. There were 423 differentially expressed genes (DEGs) found, which dramatically enriched in autophagy-related pathways. And more infiltration of mast cells, activated T cells, dendritic cells, and M1 macrophages were observed in the intestinal mucosa of active UC, while more infiltration of resting immune cells and M2 macrophages in healthy controls. WGCNA indicated that the turquoise and blue modules were the critical modules. CASP1, SERPINA1, and CCL2 have been identified as the hub autophagy-related genes of active UC, after combining DEGs and 232 autophagy-related genes from HADb with the genes of turquoise and blue modules, respectively. We further verified that CASP1, SERPINA1, and CCL2 were positively associated with active UC and served as an autophagy-related biomarker for active UC. Moreover, increased SERPINA1 in the involved intestinal mucosa was reduced in patients with active UC who responded to golimumab or glucocorticoid therapy. But, neither CASP1, SERPINA1, and CCL2 were changed by treatment of 5-aminosalicylic acid (5-ASA) and azathioprine.

Conclusion: CASP1, SERPINA1, and CCL2 are autophagy-related hub genes of active UC. And SERPINA1 may serve as a new pharmacological autophagy regulator of UC, which provides a new target for the use of small molecules targeting autophagy in the treatment of active UC.
Upregulation of IRF9 Contributes to Pulmonary Artery Smooth Muscle Cell Proliferation During Pulmonary Arterial Hypertension
Authors: Chen Yong-Jie , Li Yi , Guo Xian , Huo Bo , Chen Yue , He Yi , Xiao Rui , Zhu Xue-Hai , Jiang Ding-Sheng , Wei Xiang
Published: December 2021

Abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is a critical pathological feature in the pathogenesis of pulmonary arterial hypertension (PAH), but the regulatory mechanisms remain largely unknown. Herein, we demonstrated that interferon regulatory factor 9 (IRF9) accelerated PASMCs proliferation by regulating Prohibitin 1 (PHB1) expression and the AKT-GSK3β signaling pathway. Compared with control groups, the rats treated with chronic hypoxia (CH), monocrotaline (MCT) or sugen5416 combined with chronic hypoxia (SuHx), and mice challenged with CH had significantly thickened pulmonary arterioles and hyperproliferative PASMCs. More importantly, the protein level of IRF9 was found to be elevated in the thickened medial wall of the pulmonary arterioles in all of these PAH models. Notably, overexpression of IRF9 significantly promoted the proliferation of rat and human PASMCs, as evidenced by increased cell counts, EdU-positive cells and upregulated biomarkers of cell proliferation. In contrast, knockdown of IRF9 suppressed the proliferation of rat and human PASMCs. Mechanistically, IRF9 directly restrained PHB1 expression and interacted with AKT to inhibit the phosphorylation of AKT at thr308 site, which finally led to mitochondrial dysfunction and PASMC proliferation. Unsurprisingly, MK2206, a specific inhibitor of AKT, partially reversed the PASMC proliferation inhibited by IRF9 knockdown. Thus, our results suggested that elevation of IRF9 facilitates PASMC proliferation by regulating PHB1 expression and AKT signaling pathway to affect mitochondrial function during the development of PAH, which indicated that targeting IRF9 may serve as a novel strategy to delay the pathological progression of PAH.
Activation of TAF9 via Danshensu-Induced Upregulation of HDAC1 Expression Alleviates Non-alcoholic Fatty Liver Disease
Authors: Wang Ruiwen , Wang Zhecheng , Sun Ruimin , Fu Rong , Sun Yu , Zhu Meiyang , Geng Yunfei , Gao Dongyan , Tian Xiaofeng , Zhao Yan , Yao Jihong
Published: December 2021

Fatty acid β-oxidation is an essential pathogenic mechanism in nonalcoholic fatty liver disease (NAFLD), and TATA-box binding protein associated factor 9 (TAF9) has been reported to be involved in the regulation of fatty acid β-oxidation. However, the function of TAF9 in NAFLD, as well as the mechanism by which TAF9 is regulated, remains unclear. In this study, we aimed to investigate the signaling mechanism underlying the involvement of TAF9 in NAFLD and the protective effect of the natural phenolic compound Danshensu (DSS) against NAFLD via the HDAC1/TAF9 pathway. An in vivo model of high-fat diet (HFD)-induced NAFLD and a palmitic acid (PA)-treated AML-12 cell model were developed. Pharmacological treatment with DSS significantly increased fatty acid β-oxidation and reduced lipid droplet (LD) accumulation in NAFLD. TAF9 overexpression had the same effects on these processes both in vivo and in vitro. Interestingly, the protective effect of DSS was markedly blocked by TAF9 knockdown. Mechanistically, TAF9 was shown to be deacetylated by HDAC1, which regulates the capacity of TAF9 to mediate fatty acid β-oxidation and LD accumulation during NAFLD. In conclusion, TAF9 is a key regulator in the treatment of NAFLD that acts by increasing fatty acid β-oxidation and reducing LD accumulation, and DSS confers protection against NAFLD through the HDAC1/TAF9 pathway.
Integrated Network Pharmacology and Lipidomics to Reveal the Inhibitory Effect of Qingfei Oral Liquid on Excessive Autophagy in RSV-Induced Lung Inflammation
Authors: Lin Lili , An Li , Chen Hui , Feng Lu , Lu Mengjiang , Liu Yuling , Chu Chu , Shan Jinjun , Xie Tong , Wang Xiaorong , Wang Shouchuan
Published: December 2021

Background: Respiratory syncytial virus (RSV) can cause varying degrees of lung inflammation in children. Qingfei Oral Liquid (QF) is effective in treating childhood RSV-induced lung inflammation (RSV-LI) in clinics, but its pharmacological profiles and mechanisms remain unclear.

Methods: This study combined network Pharmacology, lipidomics, pharmacodynamics, and pathway validation to evaluate the therapeutic mechanisms of QF. Using Cytoscape (v3.8.2) and enrichment analyses from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), a global view of the putative compound-target-pathway network was created. The corresponding lipidomic profiles were then used to detect differently activated lipids, revealing the metabolic pathway, using ultra-high-performance liquid chromatography linked to hybrid Quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS). Meanwhile, the in vivo efficiency of QF, the enrichment pathway, and the excessive autophagy inhibition mechanisms were validated in RSV-infected mice models.

Results: The network pharmacology results demonstrated 117 active compounds acted directly upon 101 core targets of QF against RSV-LI. The most significantly enriched pathway was the PI3K/Akt/mTOR signaling pathway (p < 0.05). In addition, untargeted lipidomics were performed, and it was revealed that higher lung levels of DAG 30:0, DAG 30:5, DAG 32:0, DAG 16:0_18:0, DAG 17:0_17:0, DAG 34:1, DAG 36:0, DAG 36:1 in the RSV-LI group were decreased after QF administration (FDR < 0.05, FC > 1.2). Lipin-1, a key enzyme in DAG synthesis, was increased in the RSV-LI mouse model. Animal experiments further validated that QF inhibited the PI3K/Akt/mTOR signaling pathway, with lower lung levels of phosphorylated PI3K, AKT and mTOR, as well as its related proteins of lipin-1 and VPS34 (p < 0.01). Finally, pharmacodynamic investigations indicated that QF reduced airway inflammation caused by excessive autophagy by decreasing lung levels of RSV F and G proteins, Beclin-1, Atg5, and LC3B II, IL-1 and TNF-α (p < 0.05).

Conclusion: Lipidomic-based network pharmacology, along with experimental validation, may be effective approaches for illustrating the therapeutic mechanism of QF in the treatment of RSV-LI.
The Skeletal Cellular and Molecular Underpinning of the Murine Hindlimb Unloading Model
Authors: Garg Priyanka , Strigini Maura , Peurière Laura , Vico Laurence , Iandolo Donata
Published: December 2021

Bone adaptation to spaceflight results in bone loss at weight bearing sites following the absence of the stimulus represented by ground force. The rodent hindlimb unloading model was designed to mimic the loss of mechanical loading experienced by astronauts in spaceflight to better understand the mechanisms causing this disuse-induced bone loss. The model has also been largely adopted to study disuse osteopenia and therefore to test drugs for its treatment. Loss of trabecular and cortical bone is observed in long bones of hindlimbs in tail-suspended rodents. Over the years, osteocytes have been shown to play a key role in sensing mechanical stress/stimulus via the ECM-integrin-cytoskeletal axis and to respond to it by regulating different cytokines such as SOST and RANKL. Colder experimental environments (~20–22°C) below thermoneutral temperatures (~28–32°C) exacerbate bone loss. Hence, it is important to consider the role of environmental temperatures on the experimental outcomes. We provide insights into the cellular and molecular pathways that have been shown to play a role in the hindlimb unloading and recommendations to minimize the effects of conditions that we refer to as confounding factors.
Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome
Authors: Velásquez Manuela , Peláez Luisa F. , Rojas Mauricio , Narváez-Sánchez Raúl , Velásquez Jesús A. , Escudero Carlos , San Martín Sebastián , Cadavid Ángela P.
Published: December 2021

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by pregnancy morbidity or thrombosis and persistent antiphospholipid antibodies (aPL) that bind to the endothelium and induce endothelial activation, which is evidenced by the expression of adhesion molecules and the production of reactive oxygen species (ROS) and subsequent endothelial dysfunction marked by a decrease in the synthesis and release of nitric oxide (NO). These endothelial alterations are the key components for the development of severe pathological processes in APS. Patients with APS can be grouped according to the presence of other autoimmune diseases (secondary APS), thrombosis alone (thrombotic APS), pregnancy morbidity (obstetric APS), and refractoriness to conventional treatment regimens (refractory APS). Typically, patients with severe and refractory obstetric APS exhibit thrombosis and are classified as those having primary or secondary APS. The elucidation of the mechanisms underlying these alterations according to the different groups of patients with APS could help establish new therapies, particularly necessary for severe and refractory cases. Therefore, this study aimed to evaluate the differences in endothelial activation and dysfunction induced by aPL between patients with refractory obstetric APS and other APS clinical manifestations. Human umbilical vein endothelial cells (HUVECs) were stimulated with polyclonal immunoglobulin-G (IgG) from different groups of patients n = 21), including those with primary (VTI) and secondary thrombotic APS (VTII) and refractory primary (RI+), refractory secondary (RII+), and non-refractory primary (NR+) obstetric APS. All of them with thrombosis. The expression of adhesion molecules; the production of ROS, NO, vascular endothelial growth factor (VEGF), and endothelin-1; and the generation of microparticles were used to evaluate endothelial activation and dysfunction. VTI IgG induced the expression of adhesion molecules and the generation of microparticles and VEGF. RI+ IgG induced the expression of adhesion molecules and decreased NO production. RII+ IgG increased the production of microparticles, ROS, and endothelin-1 and reduced NO release. NR+ IgG increased the production of microparticles and endothelin-1 and decreased the production of VEGF and NO. These findings reveal differences in endothelial activation and dysfunction among groups of patients with APS, which should be considered in future studies to evaluate new therapies, especially in refractory cases.
Acaricidal Properties of Bio-Oil Derived From Slow Pyrolysis of Crambe abyssinica Fruit Against the Cattle Tick Rhipicephalus microplus (Acari: Ixodidae)
Authors: Mattos Camila , Andrade Juliana , Salarini Peixoto Bruno , Tavares Moraes Nayara Luiza , da Cunha Veloso Marcia Cristina , Alves Romeiro Gilberto , Folly Evelize das Chagas
Published: December 2021

Slow pyrolysis is a process for the thermochemical conversion of biomasses into bio-oils that may contain a rich chemical composition with biotechnological potential. Bio-oil produced from crambe fruits was investigated as to their acaricidal effect. Slow pyrolysis of crambe fruits was performed in a batch reactor at 400°C and chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS). The bio-oil collected was used in bioassays with larvae and engorged females of the cattle tickRhipicephalus microplus.Biological assays were performed using the larval packet test (LPT) and adult immersion test. The GC-MS of crambe fruit bio-oil revealed mainly hydrocarbons such as alkanes and alkenes, phenols, and aldehydes. The bio-oil in the LPT exhibited an LC90 of 14.4%. In addition, crambe bio-oil caused female mortality of 91.1% at a concentration of 15% and a high egg-laying inhibition. After ovary dissection of treated females, a significant reduction in gonadosomatic index was observed, indicating that bio-oil interfered in tick oogenesis. Considering these results, it may be concluded that slow pyrolysis of crambe fruit affords a sustainable and eco-friendly product for the control of cattle tickR. microplus.
Systematic Review and Meta-Analysis of Endurance Exercise Training Protocols for Mice
Authors: Massett Michael P. , Matejka Caitlyn , Kim Hyoseon
Published: December 2021

Inbred and genetically modified mice are frequently used to investigate the molecular mechanisms responsible for the beneficial adaptations to exercise training. However, published paradigms for exercise training in mice are variable, making comparisons across studies for training efficacy difficult. The purpose of this systematic review and meta-analysis was to characterize the diversity across published treadmill-based endurance exercise training protocols for mice and to identify training protocol parameters that moderate the adaptations to endurance exercise training in mice. Published studies were retrieved from PubMed and EMBASE and reviewed for the following inclusion criteria: inbred mice; inclusion of a sedentary group; and exercise training using a motorized treadmill. Fifty-eight articles met those inclusion criteria and also included a “classical” marker of training efficacy. Outcome measures included changes in exercise performance, V˙O2max, skeletal muscle oxidative enzyme activity, blood lactate levels, or exercise-induced cardiac hypertrophy. The majority of studies were conducted using male mice. Approximately 48% of studies included all information regarding exercise training protocol parameters. Meta-analysis was performed using 105 distinct training groups (i.e., EX-SED pairs). Exercise training had a significant effect on training outcomes, but with high heterogeneity (Hedges’ g=1.70, 95% CI=1.47–1.94, Tau2=1.14, I2=80.4%, prediction interval=−0.43–3.84). Heterogeneity was partially explained by subgroup differences in treadmill incline, training duration, exercise performance test type, and outcome variable. Subsequent analyses were performed on subsets of studies based on training outcome, exercise performance, or biochemical markers. Exercise training significantly improved performance outcomes (Hedges’ g=1.85, 95% CI=1.55–2.15). Subgroup differences were observed for treadmill incline, training duration, and exercise performance test protocol on improvements in performance. Biochemical markers also changed significantly with training (Hedges’ g=1.62, 95% CI=1.14–2.11). Subgroup differences were observed for strain, sex, exercise session time, and training duration. These results demonstrate there is a high degree of heterogeneity across exercise training studies in mice. Training duration had the most significant impact on training outcome. However, the magnitude of the effect of exercise training varies based on the marker used to assess training efficacy.
Advances in Cardiac Pacing: Arrhythmia Prediction, Prevention and Control Strategies
Authors: Patel Mehrie Harshad , Sampath Shrikanth , Kapoor Anoushka , Damani Devanshi Narendra , Chellapuram Nikitha , Challa Apurva Bhavana , Kaur Manmeet Pal , Walton Richard D. , Stavrakis Stavros , Arunachalam Shivaram P. , Kulkarni Kanchan
Published: December 2021

Cardiac arrhythmias constitute a tremendous burden on healthcare and are the leading cause of mortality worldwide. An alarming number of people have been reported to manifest sudden cardiac death as the first symptom of cardiac arrhythmias, accounting for about 20% of all deaths annually. Furthermore, patients prone to atrial tachyarrhythmias such as atrial flutter and fibrillation often have associated comorbidities including hypertension, ischemic heart disease, valvular cardiomyopathy and increased risk of stroke. Technological advances in electrical stimulation and sensing modalities have led to the proliferation of medical devices including pacemakers and implantable defibrillators, aiming to restore normal cardiac rhythm. However, given the complex spatiotemporal dynamics and non-linearity of the human heart, predicting the onset of arrhythmias and preventing the transition from steady state to unstable rhythms has been an extremely challenging task. Defibrillatory shocks still remain the primary clinical intervention for lethal ventricular arrhythmias, yet patients with implantable cardioverter defibrillators often suffer from inappropriate shocks due to false positives and reduced quality of life. Here, we aim to present a comprehensive review of the current advances in cardiac arrhythmia prediction, prevention and control strategies. We provide an overview of traditional clinical arrhythmia management methods and describe promising potential pacing techniques for predicting the onset of abnormal rhythms and effectively suppressing cardiac arrhythmias. We also offer a clinical perspective on bridging the gap between basic and clinical science that would aid in the assimilation of promising anti-arrhythmic pacing strategies.
Carry-Over Effects of Desiccation Stress on the Oxidative Status of Fasting Anuran Juveniles
Authors: Prokić Marko D. , Petrović Tamara G. , Gavrilović Branka R. , Despotović Svetlana G. , Gavrić Jelena P. , Kijanović Ana , Tomašević Kolarov Nataša , Vukov Tanja , Radovanović Tijana B.
Published: December 2021

Amphibians are sensitive to deteriorating environmental conditions, especially during transition to a terrestrial environment which is full of uncertainties. Harsh conditions, such as desiccation during earlier stages, affect different larval traits with possible carry-over effects on juvenile and adult life histories. The first consequences of the effects can be seen in juveniles in the challenges to find food and the ability to survive without it in a terrestrial habitat. Body size and the internal energy reserves acquired during the larval phase play an important role in this period. Herein, we tested how different water regimes (low water availability, desiccation and constant high-water availability) during larval development reflect on the oxidative status and ability of yellow belly toad (Bombina variegata) juveniles to endure short-term fasting. The desiccation regime significantly reduced the body size of metamorphs. The same was observed after 2 weeks of fasting, while the feeding treatment reduced differences mostly in the body mass of individuals from different water regimes. This was the result of a greater gain in mass in juveniles pre-exposed to desiccation. Pre-exposure to desiccation also modified the parameters of the antioxidant system (AOS) under feeding conditions, leading to higher values of superoxide dismutase, glutathione reductase and glutathione S-transferase, glutathione and sulfhydryl group concentrations, and lower glutathione peroxidase in comparison to juveniles reared under constant water. The increase in the AOS of juveniles can be considered as a physiological carry-over effect of desiccation, probably as the result of compensatory growth and/or earlier exposure to chronic stress. However, water levels during larval development did not exert significant effects on the oxidative status of juveniles subjected to food unavailability. Fasting juveniles, both control and desiccated, were exposed to oxidative stress, significantly higher lipid peroxide concentrations, lower superoxide dismutase, glutathione peroxidase, glutathione S-transferase, glutathione and sulfhydryl group values in comparison to feeding individuals. The lack of food in juvenile anurans activated the AOS response in the same manner, regardless of body size and stress pre-exposure, suggesting that the generally accepted hypothesis about the influence of metamorphic body size on the fitness of the postmetamorphic stage should be tested further.
Post-dynamic Resistance Exercise Hypotension: Exploring Individual Responses and Predictors
Authors: Fecchio Rafael Y. , Queiroz Andreia C. C. , Ritti-Dias Raphael , Costa Eduardo Caldas , Forjaz Cláudia L. M.
Published: December 2021

Background: Post-dynamic resistance exercise hypotension (PREH) has been largely demonstrated. However, little is known regarding the interindividual variation of PREH magnitude and its predictors (i.e. factors of influence).

Aims: To assess the interindividual variation of PREH and its predictors related to the characteristics of the individuals and the exercise protocol.

Methods: This study retrospectively analysed data from 131 subjects included in seven controlled trials about PREH (including at least one dynamic resistance exercise and one control session) conducted by two research laboratories. The interindividual variation was assessed by the standard deviation of the individual responses (SDIR), and linear regression analyses were conducted to explore the predictors.

Results: PREH showed moderate interindividual variation for systolic (SBP, SDIR=4.4mmHg; 0.35 standardised units) and diastolic blood pressures (DBP, SDIR=3.6mmHg; 0.32 standardised units). For systolic PREH, multivariate regression analysis (R2=0.069) revealed higher baseline SBP (B=−0.157, p=0.008) and higher number of sets (B=−3.910, p=0.041) as significant predictors. For diastolic PREH, multivariate regression analysis (R2=0.174) revealed higher baseline DBP (B=−0.191, p=0.001) and higher exercise volume (i.e. number of exercises *sets per exercise *repetitions per sets >150; B=−4.212, p=0.001) as significant predictors.

Conclusion: PREH has a considerable interindividual variation. Greater PREH magnitude is observed in individuals with higher baseline blood pressure and after exercise protocols that comprehend higher number of sets and exercise volume.
A Comparative Study on the Hemodynamic Performance Within Cross and Non-cross Stent-Grafts for Abdominal Aortic Aneurysms With an Angulated Neck
Authors: Qing Ming , Qiu Yue , Wang Jiarong , Zheng Tinghui , Yuan Ding
Published: December 2021

Objectives: Cross-limb stent grafts for endovascular aneurysm repair (EVAR) are often employed for abdominal aortic aneurysms (AAAs) with significant aortic neck angulation. Neck angulation may be coronal or sagittal; however, previous hemodynamic studies of cross-limb EVAR stent grafts (SGs) primarily utilized simplified planar neck geometries. This study examined the differences in flow patterns and hemodynamic parameters between crossed and non-crossed limb SGs at different spatial neck angulations.

Methods: Ideal models consisting of 13 cross and 13 non-cross limbs were established, with coronal and sagittal angles ranging from 0 to 90°. Computational fluid dynamics (CFD) was used to capture the hemodynamic information, and the differences were compared.

Results: With regards to the pressure drop index, the maximum difference caused by the configuration and angular direction was 4.6 and 8.0%, respectively, but the difference resulting from the change in aneurysm neck angle can reach 27.1%. With regards to the SAR-TAWSS index, the maximum difference caused by the configuration and angular direction was 7.8 and 9.8%, respectively, but the difference resulting from the change in aneurysm neck angle can reach 26.7%. In addition, when the aneurysm neck angle is lower than 45°, the configuration and angular direction significantly influence the OSI and helical flow intensity index. However, when the aneurysm neck angle is greater than 45°, the hemodynamic differences of each model at the same aneurysm neck angle are reduced.

Conclusion: The main factor affecting the hemodynamic index was the angle of the aneurysm neck, while the configuration and angular direction had little effect on the hemodynamics. Furthermore, when the aneurysm neck was greatly angulated, the cross-limb technique did not increase the risk of thrombosis.
Arabidopsis Target of Rapamycin Coordinates With Transcriptional and Epigenetic Machinery to Regulate Thermotolerance
Authors: Sharma Mohan , Jamsheer K. Muhammed , Shukla Brihaspati Narayan , Sharma Manvi , Awasthi Prakhar , Mahtha Sanjeet Kumar , Yadav Gitanjali , Laxmi Ashverya
Published: December 2021

Global warming exhibits profound effects on plant fitness and productivity. To withstand stress, plants sacrifice their growth and activate protective stress responses for ensuring survival. However, the switch between growth and stress is largely elusive. In the past decade, the role of the target of rapamycin (TOR) linking energy and stress signalling is emerging. Here, we have identified an important role of Glucose (Glc)-TOR signalling in plant adaptation to heat stress (HS). Glc via TOR governs the transcriptome reprogramming of a large number of genes involved in heat stress protection. Downstream to Glc-TOR, the E2Fa signalling module regulates the transcription of heat shock factors through direct recruitment of E2Fa onto their promoter regions. Also, Glc epigenetically regulates the transcription of core HS signalling genes in a TOR-dependent manner. TOR acts in concert with p300/CREB HISTONE ACETYLTRANSFERASE1 (HAC1) and dictates the epigenetic landscape of HS loci to regulate thermotolerance. Arabidopsis plants defective in TOR and HAC1 exhibited reduced thermotolerance with a decrease in the expression of core HS signalling genes. Together, our findings reveal a mechanistic framework in which Glc-TOR signalling through different modules integrates stress and energy signalling to regulate thermotolerance.
ecc_finder: A Robust and Accurate Tool for Detecting Extrachromosomal Circular DNA From Sequencing Data
Authors: Zhang Panpan , Peng Haoran , Llauro Christel , Bucher Etienne , Mirouze Marie
Published: December 2021

Extrachromosomal circular DNA (eccDNA) has been observed in different species for decades, and more and more evidence shows that this specific type of DNA molecules may play an important role in rapid adaptation. Therefore, characterizing the full landscape of eccDNA has become critical, and there are several protocols for enriching eccDNAs and performing short-read or long-read sequencing. However, there is currently no available bioinformatic tool to identify eccDNAs from Nanopore reads. More importantly, the current tools based on Illumina short reads lack an efficient standardized pipeline notably to identify eccDNA originating from repeated loci and cannot be applied to very large genomes. Here, we introduce a comprehensive tool to solve both of these two issues.1 Applying ecc_finder to eccDNA-seq data (either mobilome-seq, Circle-Seq and CIDER-seq) from Arabidopsis, human, and wheat (with genome sizes ranging from 120Mb to 17 Gb), we document the improvement of computational time, sensitivity, and accuracy and demonstrate ecc_finder wide applicability and functionality.
Novel Quantitative Trait Loci for Grain Cadmium Content Identified in Hard White Spring Wheat
Authors: Qiao Ling , Wheeler Justin , Wang Rui , Isham Kyle , Klassen Natalie , Zhao Weidong , Su Meng , Zhang Junli , Zheng Jun , Chen Jianli
Published: December 2021

Cadmium (Cd) is a heavy metal that can cause a variety of adverse effects on human health, including cancer. Wheat comprises approximately 20% of the human diet worldwide; therefore, reducing the concentrations of Cd in wheat grain will have significant impacts on the intake of Cd in food products. The tests for measuring the Cd content in grain are costly, and the content is affected significantly by soil pH. To facilitate breeding for low Cd content, this study sought to identify quantitative trait loci (QTL) and associated molecular markers that can be used in molecular breeding. One spring wheat population of 181 doubled haploid lines (DHLs), which was derived from a cross between two hard white spring wheat cultivars “UI Platinum” (UIP) and “LCS Star” (LCS), was assessed for the Cd content in grain in multiple field trials in Southeast Idaho, United States. Three major QTL regions, namely, QCd.uia2-5B, QCd.uia2-7B, and QCd.uia2-7D, were identified on chromosomes 5B, 7B, and 7D, respectively. All genes in these three QTL regions were identified from the NCBI database. However, three genes related to the uptake and transport of Cd were used in the candidate gene analysis. The sequences of TraesCS5B02G388000 (TaHMA3) in the QCd.uia2-5B region and TraesCS7B02G320900 (TaHMA2) and TraesCS7B02G322900 (TaMSRMK3) in the QCd.uia2-7B region were compared between UIP and LCS. TaHMA2 on 7B is proposed for the first time as a candidate gene for grain Cd content in wheat. A KASP marker associated with this gene was developed and it will be further validated in near-isogenic lines via a gene-editing system in future studies.
Damage Signaling by Extracellular Nucleotides: A Role for Cyclic Nucleotides in Elevating Cytosolic Free Calcium?
Authors: Sun Jian , Ning Youzheng , Wang Limin , Wilkins Katie A. , Davies Julia M.
Published: December 2021

Extracellular ATP (eATP) is now held to be a constitutive damage-associated molecular pattern (DAMP) that is released by wounding, herbivory or pathogen attack. The concentration of eATP must be tightly regulated as either depletion or overload leads to cell death. In Arabidopsis thaliana, sensing of eATP is by two plasma membrane legume-like lectin serine–threonine receptor kinases (P2K1 and P2K2), although other receptors are postulated. The transcriptional response to eATP is dominated by wound- and defense-response genes. Wounding and pathogen attack can involve the cyclic nucleotides cyclic AMP (cAMP) and cyclic GMP (cGMP) which, in common with eATP, can increase cytosolic-free Ca2+ as a second messenger. This perspective on DAMP signaling by eATP considers the possibility that the eATP pathway involves production of cyclic nucleotides to promote opening of cyclic nucleotide-gated channels and so elevates cytosolic-free Ca2+. In silico analysis of P2K1 and P2K2 reveals putative adenylyl and guanylyl kinase sequences that are the hallmarks of “moonlighting” receptors capable of cAMP and cGMP production. Further, an Arabidopsis loss of function cngc mutant was found to have an impaired increase in cytosolic-free Ca2+ in response to eATP. A link between eATP, cyclic nucleotides, and Ca2+ signaling therefore appears credible.
Critical Conditions Identification for Online Purchase Intention of Fruits: A Fuzzy-Set Qualitative Comparative Analysis
Authors: Wang Can , Chen Fangyu , Yi Feiteng , Wei Yongchang
Published: December 2021

With the development of Internet technology, e-commerce platforms have emerged one after another, and the competition of the fruit e-commerce market is increasingly intensified. How to boost customer demand by improving their purchase intention has become a key issue. The study identified the critical conditions leading to high purchase intention of fruits through fuzzy-set qualitative comparative analysis. The empirical analysis was conducted based on an online questionnaire of 344 Internet users. The results reveal that high purchase intention comes from high fruit quality, high fruit price concessions and supply service, and low perceived risk (peripheral conditions). In addition, high purchase intention can also be realized from high fruit quality, high fruit price concessions, high supply service, and high website information quality (peripheral conditions). This study provides more nuanced thinking of how to improve online purchase intention of fruits.
Support From Parents, Peers, and Teachers Is Differently Associated With Middle School Students’ Well-Being
Authors: Hoferichter Frances , Kulakow Stefan , Hufenbach Miriam C.
Published: December 2021

Parents, peers, and teachers provide a powerful context for school students’ well-being. However, a detailed and systematic analysis of how parental, peer, and teacher support relate to students’ well-being, measured by the dimensions self-worth, psychological and physical well-being, is still missing. To address this research gap, the following study investigates 733 adolescent German students from grades 7 and 8 (Mage= 13.97,SD= 0.41, 52% girls) with respect to their perceived supportive relationships at home and within the school context. The study considers gender, socioeconomic status, and school form as potential confounders. The results of the structural equation model, analyzed with the statistical software R, indicate that perceived teacher support was positively related to students’ self-worth and physical well-being, while peer support was related to psychological well-being. Students who perceived their parents as supportive reported higher well-being with respect to all three dimensions investigated.
Reasoning Talk at Chinese Families’ Dinner Table: Across Three Generations and Different Communicative Contexts
Authors: Liu Lifang , Zheng Feiyi , Sheng Ling , Hao Yijun , Hu Jiangbo
Published: December 2021

This study examines the feature of reasoning talk used by 37 Chinese families at the dinner table across three generations with the background of co-parenting and in consideration of different communicative contexts. Drawing upon Hasan’s semantic framework, reasons were mainly coded as logical or social types. We categorize the communicative context of reasoning talk into contextualized (meal-related) and decontextualized topics. When the proportion of social reasoning was found slightly higher than that of logical reasoning, the families’ reasoning talk account for only 3.85% of the total language. Specifically, the count of mothers’ total reasoning talk was significantly above other family members, while there were no significant differences among the other participants. The effect of the communicative contexts on family members’ social reasoning was found. The reasoning talk grounded on local rules (family-made rules) and coercive power occurred significantly more frequently in contextualized than decontextualized context. A higher rate of local-rule grounded reasoning talk of all family members appeared in contextualized than decontextualized context, and this gap was particularly obvious among mothers. These findings reveal the significant role of mothers in family communications and confirm the pedagogical values of decontextualized communicative context for promoting children’s learning opportunities at the dinner table.
Is Familism a Motivator or Stressor? Relationships Between Confucian Familism, Emotional Labor, Work-Family Conflict, and Emotional Exhaustion Among Chinese Teachers
Authors: Zhu Xiaoshuang , Tian Guoxiu , Yin Hongbiao , He Wenjie
Published: December 2021

To reveal the cultural effect in the job demands-resources model, this study examined how Confucian familism, emotional labor, and work-family conflict (WFC) explain the variance in teachers’ emotional exhaustion, with a focus on the mediating roles of emotional labor and WFC. With a sample of 3,312 teachers in China, the results of this study revealed that surface acting and expression of naturally felt emotion (ENFE) and WFC mediated the relationship between familism and emotional exhaustion. Moreover, familism positively predicted deep acting, ENFE, WFC, and emotional exhaustion, while negatively predicted surface acting. These findings suggest that Confucian familism may play the dual role of motivator and stressor for Chinese teachers’ emotional labor and well-being. This study contributes to the job demands-resources theory by revealing the important role of cultural traditions and provides valuable information for interventions to sustain teacher well-being.
The Association Between Regular Physical Exercise, Sleep Patterns, Fasting, and Autophagy for Healthy Longevity and Well-Being: A Narrative Review
Authors: Min Sicheng , Masanovic Bojan , Bu Te , Matic Radenko M. , Vasiljevic Ivan , Vukotic Marina , Li Jiaomu , Vukovic Jovan , Fu Tao , Jabucanin Blazo , Bujkovic Rajko , Popovic Stevo
Published: December 2021

This narrative review of the literature assessed whether regular physical exercise and sleep patterns, fasting and autophagy, altogether can be an adequate strategy for achieving healthy longevity and well-being within different stage of life. There are a large number of studies dealing with well-being and healthy longevity; however, few of them have given us a specific formula for how to live long and healthy. Despite all the advances that have been made to create adequate physical exercise programs, sleep patterns or nutritional protocols, the relation between different types of fasting, nutritional supplementation as well as regular physical exercise and sleep patterns have not yet been satisfactorily resolved to cause the best effects of autophagy and, therefore, well-being and healthy longevity. In this way, future studies should clarify more efficiently the relationship between these variables to understand the association between regular physical exercise, sleep patterns, fasting and autophagy for healthy longevity and well-being.
The Role of Social and Emotional Adjustment in Mediating the Relationship Between Early Experiences and Different Language Outcomes
Authors: Law James , Tamayo Nathalie , Mckean Cristina , Rush Robert
Published: December 2021

Background: Studies have highlighted the relationship between early childhood experiences and later language and communication skills on the one hand and social and emotional adjustment on the other. Less is known about this relationship between different types of early experiences and their relationship to different communication skills over time. Equally important is the extent to which the child's behaviour is related to later outcomes affecting the relationship between the child's environment and aspects of their communication development.

Method: Drawing on data from 5,000 children in Growing Up in Scotland, a representative sample of children born in 2003. This paper looks are the differential relationships between home learning environment (HLE) (reads books/storeys, engages in painting or drawing, reads nursery rhymes and teaches letter/shapes and parental mental health (PMH) (Depression, Anxiety and Stress Scale (DASS) in the first year of life and both structural language skills (“Listening Comprehension” and “Expressive Vocabulary” subtests of The Wechsler Individual Achievement Tests) and pragmatic competence (The Children's Communication Checklist) at 11 years and explores the extent to which they are mediated by social and emotional adjustment at school entry.

Results: PMH was associated with pragmatics but not listening comprehension or vocabulary. By contrast HLE was associated with all three measures of communication. In the final mediated model social and emotional adjustment mediated the relationship between PMH and all three measures of communication. The mediation was statistically significant for the relationship between HLE and both pragmatics and listening comprehension but not for expressive vocabulary. The results are discussed in terms of the relationships concerned and what they tell us about the potential for targeted early interventions.

Conclusions: The mediating role of socio-emotional adjustment at school entry points to the need for careful monitoring of children's social and emotional development in primary and middle childhood. Services and policy aimed at improving child outcomes through improving home learning environments must work hand in hand with those responsible for offering support for the mental health, social-emotional adjustment and wellbeing of parents and children from birth and into the school years.
Prediction of Suicidality According to Serum Folate Levels in Depressive Patients Receiving Stepwise Pharmacotherapy
Authors: Kim Jae-Min , Kim Ha-Yeon , Lee Hee-Joon , Kim Ju-Wan , Kang Hee-Ju , Kim Sung-Wan , Shin Il-Seon , Chun Byeong Jo , Stewart Robert
Published: December 2021

Background: The effects of serum folate levels on suicidal behavior, strongly associated with depression, have not been investigated. Therefore, this study investigated the associations between serum folate levels and suicidal behavior in patients with depressive disorders.

Methods: Serum folate levels were measured at baseline in 1,094 patients with depressive disorder, 884 of whom were followed during a 12-month period of stepwise pharmacotherapy. Suicidal behaviors evaluated at baseline were (i) previous suicide attempt and (ii) baseline suicidal severity; behaviors evaluated at follow-up were (iii) increased suicidal severity and iv) fatal/non-fatal suicide attempt. Associations of serum folate levels with four types of suicidal behaviors were analyzed using logistic regression models after adjustment for relevant covariates; they were also examined using area under receiver operating characteristic (AUROC) curve analyses.

Results: Reduced serum folate levels (<6.0 ng/mL) were independently associated with all four types of suicidal behaviors. AUROC curve analyses indicated that discriminant or prognostic values of reduced serum folate levels were fair for fatal/non-fatal suicide attempt during follow-up, whereas they were modest for previous suicide attempt, baseline suicidal severity, and increased suicidal severity.

Conclusions: Serum folate levels could serve as a biomarker of suicidal behavior in depressive patients. However, it should be used as an adjunct rather than a substitute for prediction of suicidal behavior considering its low prognostic values. Further replication studies are needed for its clinical utilization.
The 4-Level Approach: Prevention of Suicidal Behaviour Through Community-Based Intervention
Authors: Hegerl Ulrich , Heinz Ines , O'Connor Ainslie , Reich Hanna
Published: December 2021

Due to the many different factors contributing to diagnostic and therapeutic deficits concerning depression and the risk of suicidal behaviour, community-based interventions combining different measures are considered the most efficient way to address these important areas of public health. The network of the European Alliance Against Depression has implemented in more than 120 regions within and outside of Europe community-based 4-level-interventions that combine activities at four levels: (i) primary care, (ii) general public, (iii) community facilitators and gatekeepers (e.g., police, journalists, caregivers, pharmacists, and teachers), and (iv) patients, individuals at high risk and their relatives. This review will discuss lessons learned from these broad implementation activities. These include targeting depression and suicidal behaviour within one approach; being simultaneously active on the four different levels; promoting bottom-up initiatives; and avoiding any cooperation with the pharmaceutical industry for reasons of credibility.
Frontotemporal Dementia and Late-Onset Bipolar Disorder: The Many Directions of a Busy Road
Authors: Maia da Silva Mari N. , Porto Fábio Henrique de Gobbi , Lopes Pedro Maranhão Gomes , Sodré de Castro Prado Catarina , Frota Norberto Anízio Ferreira , Alves Candida Helena Lopes , Alves Gilberto Sousa
Published: December 2021

It is a common pathway for patients with the behavioral variant of frontotemporal dementia (bvFTD) to be first misdiagnosed with a primary psychiatric disorder, a considerable proportion of them being diagnosed with bipolar disorder (BD). Conversely, not rarely patients presenting in late life with a first episode of mania or atypically severe depression are initially considered to have dementia before the diagnosis of late-onset BD is reached. Beyond some shared features that make these conditions particularly prone to confusion, especially in the elderly, the relationship between bvFTD and BD is far from simple. Patients with BD often have cognitive complaints as part of their psychiatric disorder but are at an increased risk of developing dementia, including FTD. Likewise, apathy and disinhibition, common features of depression and mania, respectively, are among the core features of the bvFTD syndrome, not to mention that depression may coexist with dementia. In this article, we take advantage of the current knowledge on the neurobiology of these two nosologic entities to review their historical and conceptual interplay, highlighting the clinical, genetic and neuroimaging features that may be shared by both disorders or unique to each of them.