bluuebunny/crossref_metadata_2025 huggingface dataset:
Stiffer Spleen Predicts Higher Bone Marrow Fibrosis and Higher JAK2 Allele Burden in Patients With Myeloproliferative Neoplasms
Authors: Moia Riccardo , Cittone Micol Giulia , Boggione Paola , Manfredi Giulia Francesca , Favini Chiara , Awikeh Bassel , Pedrinelli Anita Rebecca , Mahmoud Abdurraouf Mokhtar , Nicolosi Maura , Bellan Mattia , Sainaghi Pier Paolo , Pirisi Mario , Gaidano Gianluca , Patriarca Andrea , Rigamonti Cristina
Published: October 2021

A total of 63 myeloproliferative neoplasms [MPN; 9 polycythemia vera (PV), 32 essential thrombocythemia (ET), and 22 myelofibrosis (MF)] underwent spleen stiffness (SS) measurement by vibration-controlled transient elastography equipped with a novel spleen-dedicated module. Higher SS values significantly correlated with grade 2-3 bone marrow (BM) fibrosis (p=0.035), with hemoglobin level <10 g/dl (p=0.014) and with white blood cells ≥10,000/μl (p=0.008). Median SS was significantly higher in MF patients compared to ET and PV (p=0.015). SS also correlated with higher JAK2 variant allele frequency (p=0.02). This study identifies SS as a potential noninvasive tool that reflects BM fibrosis and the mutational burden in MPN.
Impact of the COVID-19 Pandemic on Stress, Sleep, and Oral Health in University Students
Authors: Cerqueira Thaissa Reis do Carmo , Batista Sayene Garcia , de Mello Elson Braga , DosSantos Marcos Fabio , Tuñas Inger Teixeira de Campos
Published: October 2021

Background:The COVID-19 pandemic, a disease caused by Sars-CoV-2, has become a worldwide stressor, especially as it represents a new viral infection, which spreads quickly and easily, without prior knowledge about vaccination, and absence, to this moment, of a medication that is totally effective against the disease.

Objective:The aim of this observational study was to provide a general evaluation, through a questionnaire applied to students in the health field of the Federal University of Rio de Janeiro, on the psychological impacts and behavioral changes generated by the COVID-19 pandemic on oral health, especially the triggering or exacerbation of bruxism and temporomandibular disorders (TMD).

Methods:In order to verify the impacts of the pandemic on the health of UFRJ healthcare students, a non-randomized survey was performed with 370 students.

Results:It was found that 72% of the students had their sleep routine altered, 65% had greater difficulty in keeping their spirits up, there was a statistically significant increase in emotional stress, headaches, and daytime teeth clenching.

Conclusion:It was possible to conclude that the outbreak of COVID-19 resulted in psychological, physiological and behavioral impacts on students.
Pharmacology, Toxicology, and Metabolism of Sennoside A, A Medicinal Plant-Derived Natural Compound
Authors: Le Jiamei , Ji Houlin , Zhou Xiaoxiao , Wei Xindong , Chen Yifan , Fu Yi , Ma Yujie , Han Qiuqin , Sun Yongning , Gao Yueqiu , Wu Hailong
Published: October 2021

Sennoside A (SA) is a natural dianthrone glycoside mainly from medicinal plants of Senna and Rhubarb, and used as a folk traditional irritant laxative and slimming health food. Accumulating evidences suggest that SA possesses numerous pharmacological properties, such as laxative, anti-obesity, hypoglycemic, hepatoprotective, anti-fibrotic, anti-inflammatory, anti-tumor, anti-bacterial, anti-fungal, anti-viral, and anti-neurodegenerative activities. These pharmacological effects lay the foundation for its potential application in treating a variety of diseases. However, numerous published studies suggest that a long-term use of SA in large doses may have some adverse effects, including the occurrence of melanosis coli and carcinogenesis of colon cancer, thereby limiting its clinical use. It remains to be established whether SA or its metabolites are responsible for the pharmacological and toxicity effects. In this review, the latest advances in the pharmacology, toxicology, and metabolism of SA were summarizedbased on its biological characteristics and mechanism.
Monitoring Intra-cellular Tacrolimus Concentrations in Solid Organ Transplantation: Use of Peripheral Blood Mononuclear Cells and Graft Biopsy Tissue
Authors: Sallustio Benedetta C.
Published: October 2021

Tacrolimus is an essential immunosuppressant for the prevention of rejection in solid organ transplantation. Its low therapeutic index and high pharmacokinetic variability necessitates therapeutic drug monitoring (TDM) to individualise dose. However, rejection and toxicity still occur in transplant recipients with blood tacrolimus trough concentrations (C0) within the target ranges. Peripheral blood mononuclear cells (PBMC) have been investigated as surrogates for tacrolimus’s site of action (lymphocytes) and measuring allograft tacrolimus concentrations has also been explored for predicting rejection or nephrotoxicity. There are relatively weak correlations between blood and PBMC or graft tacrolimus concentrations. Haematocrit is the only consistent significant (albeit weak) determinant of tacrolimus distribution between blood and PBMC in both liver and renal transplant recipients. In contrast, the role of ABCB1 pharmacogenetics is contradictory. With respect to distribution into allograft tissue, studies report no, or poor, correlations between blood and graft tacrolimus concentrations. Two studies observed no effect of donor ABCB1 or CYP3A5 pharmacogenetics on the relationship between blood and renal graft tacrolimus concentrations and only one group has reported an association between donor ABCB1 polymorphisms and hepatic graft tacrolimus concentrations. Several studies describe significant correlations between in vivo PBMC tacrolimus concentrations and ex vivo T-cell activation or calcineurin activity. Older studies provide evidence of a strong predictive value of PBMC C0 and allograft tacrolimus C0 (but not blood C0) with respect to rejection in liver transplant recipients administered tacrolimus with/without a steroid. However, these results have not been independently replicated in liver or other transplants using current triple maintenance immunosuppression. Only one study has reported a possible association between renal graft tacrolimus concentrations and acute tacrolimus nephrotoxicity. Thus, well-designed and powered prospective clinical studies are still required to determine whether measuring tacrolimus PBMC or graft concentrations offers a significant benefit compared to current TDM.
Modulating Neurological Complications of Emerging Infectious Diseases: Mechanistic Approaches to Candidate Phytochemicals
Authors: Fakhri Sajad , Mohammadi Pour Pardis , Piri Sana , Farzaei Mohammad Hosein , Echeverría Javier
Published: October 2021

Growing studies are revealing the critical manifestations of influenza, dengue virus (DENV) infection, Zika virus (ZIKV) disease, and Ebola virus disease (EVD) as emerging infectious diseases. However, their corresponding mechanisms of major complications headed for neuronal dysfunction are not entirely understood. From the mechanistic point of view, inflammatory/oxidative mediators are activated during emerging infectious diseases towards less cell migration, neurogenesis impairment, and neuronal death. Accordingly, the virus life cycle and associated enzymes, as well as host receptors, cytokine storm, and multiple signaling mediators, are the leading players of emerging infectious diseases. Consequently, chemokines, interleukins, interferons, carbohydrate molecules, toll-like receptors (TLRs), and tyrosine kinases are leading orchestrates of peripheral and central complications which are in near interconnections. Some of the resulting neuronal manifestations have attracted much attention, including inflammatory polyneuropathy, encephalopathy, meningitis, myelitis, stroke, Guillain-Barré syndrome (GBS), radiculomyelitis, meningoencephalitis, memory loss, headaches, cranial nerve abnormalities, tremor, and seizure. The complex pathophysiological mechanism behind the aforementioned complications urges the need for finding multi-target agents with higher efficacy and lower side effects. In recent decades, the natural kingdom has been highlighted as promising neuroprotective natural products in modulating several dysregulated signaling pathways/mediators. The present study provides neuronal manifestations of some emerging infectious diseases and underlying pathophysiological mechanisms. Besides, a mechanistic-based strategy is developed to introduce candidate natural products as promising multi-target agents in combating major dysregulated pathways towards neuroprotection in influenza, DENV infection, ZIKV disease, and EVD.
Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung Cancer
Authors: Ye Jiahui , Mao Longfei , Xie Luoyijun , Zhang Rongjun , Liu Yulin , Peng Lizeng , Yang Jianxue , Li Qingjiao , Yuan Miaomiao
Published: October 2021

Chemotherapy is the most common clinical treatment for non-small cell lung cancer (NSCLC), but low efficiency and high toxicity of current chemotherapy drugs limit their clinical application. Therefore, it is urgent to develop hypotoxic and efficient chemotherapy drugs. Theophylline, a natural compound, is safe and easy to get, and it can be used as a modified scaffold structure and hold huge potential for developing safe and efficient antitumor drugs. Herein, we linked theophylline with different azide compounds to synthesize a new type of 1,2,3-triazole ring-containing theophylline derivatives. We found that some theophylline1,2,3-triazole compounds showed a good tumor-suppressive efficacy. Especially, derivative d17 showed strong antiproliferative activity against a variety of cancer cells in vitro, including H460, A549, A2780, LOVO, MB-231, MCF-7, OVCAR3, SW480, and PC-9. It is worth noting that the two NSCLC cell lines H460 H and A549 are sensitive to compound d17 particularly, with IC50 of 5.929 ± 0.97 μM and 6.76 ± 0.25 μM, respectively. Compound d17 can significantly induce cell apoptosis by increasing the ratio of apoptotic protein Bax/Bcl-2 by downregulating the expression of phosphorylated Akt protein, and it has little toxicity to normal hepatocyte cells LO2 at therapeutic concentrations. These data indicate that these theophylline acetic acid-1,2,3-triazole derivatives may be potential drug candidates for anti-NSCLC and are worthy of further study.
Magnolol Attenuates Right Ventricular Hypertrophy and Fibrosis in Hypoxia-Induced Pulmonary Arterial Hypertensive Rats Through Inhibition of the JAK2/STAT3 Signaling Pathway
Authors: Fu Minyi , Luo Fangmei , Wang Eli , Jiang Yueping , Liu Shao , Peng Jun , Liu Bin
Published: October 2021

Right ventricular (RV) remodeling is one of the essential pathological features in pulmonary arterial hypertension (PAH). RV hypertrophy or fibrosis are the leading causes of RV remodeling. Magnolol (6, 6′, 7, 12-tetramethoxy-2,2′-dimethyl-1-β-berbaman, C18H18O2) is a compound isolated from Magnolia Officinalis. It possesses multiple pharmacological activities, such as anti-oxidation and anti-inflammation. This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH. In vivo, male Sprague Dawley rats were exposed to 10% O2 for 4 weeks to establish an RV remodeling model, which showed hypertrophic and fibrotic features (increases of Fulton index, cellular size, hypertrophic and fibrotic marker expression), accompanied by an elevation in phosphorylation levels of JAK2 and STAT3; these changes were attenuated by treating with magnolol. In vitro, the cultured H9c2 cells or cardiac fibroblasts were exposed to 3% O2 for 48 h to induce hypertrophy or fibrosis, which showed hypertrophic (increases in cellular size as well as the expression of ANP and BNP) or fibrotic features (increases in the expression of collagen Ⅰ, collagen Ⅲ, and α-SMA). Administration of magnolol and TG-101348 or JSI-124 (both JAK2 selective inhibitors) could prevent myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. Based on these observations, we conclude that magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway. Magnolol may possess the potential clinical value for PAH therapy.
Carnitine Palmitoyltransferase System: A New Target for Anti-Inflammatory and Anticancer Therapy?
Authors: Wang Muyun , Wang Kun , Liao Ximing , Hu Haiyang , Chen Liangzhi , Meng Linlin , Gao Wei , Li Qiang
Published: October 2021

Lipid metabolism involves multiple biological processes. As one of the most important lipid metabolic pathways, fatty acid oxidation (FAO) and its key rate-limiting enzyme, the carnitine palmitoyltransferase (CPT) system, regulate host immune responses and thus are of great clinical significance. The effect of the CPT system on different tissues or organs is complex: the deficiency or over-activation of CPT disrupts the immune homeostasis by causing energy metabolism disorder and inflammatory oxidative damage and therefore contributes to the development of various acute and chronic inflammatory disorders and cancer. Accordingly, agonists or antagonists targeting the CPT system may become novel approaches for the treatment of diseases. In this review, we first briefly describe the structure, distribution, and physiological action of the CPT system. We then summarize the pathophysiological role of the CPT system in chronic obstructive pulmonary disease, bronchial asthma, acute lung injury, chronic granulomatous disease, nonalcoholic fatty liver disease, hepatic ischemia–reperfusion injury, kidney fibrosis, acute kidney injury, cardiovascular disorders, and cancer. We are also concerned with the current knowledge in either preclinical or clinical studies of various CPT activators/inhibitors for the management of diseases. These compounds range from traditional Chinese medicines to novel nanodevices. Although great efforts have been made in studying the different kinds of CPT agonists/antagonists, only a few pharmaceuticals have been applied for clinical uses. Nevertheless, research on CPT activation or inhibition highlights the pharmacological modulation of CPT-dependent FAO, especially on different CPT isoforms, as a promising anti-inflammatory/antitumor therapeutic strategy for numerous disorders.
Glucosinolates From Cruciferous Vegetables and Their Potential Role in Chronic Disease: Investigating the Preclinical and Clinical Evidence
Authors: Connolly Emma L. , Sim Marc , Travica Nikolaj , Marx Wolfgang , Beasy Gemma , Lynch Gordon S. , Bondonno Catherine P. , Lewis Joshua R. , Hodgson Jonathan M. , Blekkenhorst Lauren C.
Published: October 2021

An increasing body of evidence highlights the strong potential for a diet rich in fruit and vegetables to delay, and often prevent, the onset of chronic diseases, including cardiometabolic, neurological, and musculoskeletal conditions, and certain cancers. A possible protective component, glucosinolates, which are phytochemicals found almost exclusively in cruciferous vegetables, have been identified from preclinical and clinical studies. Current research suggests that glucosinolates (and isothiocyanates) act via several mechanisms, ultimately exhibiting anti-inflammatory, antioxidant, and chemo-protective effects. This review summarizes the current knowledge surrounding cruciferous vegetables and their glucosinolates in relation to the specified health conditions. Although there is evidence that consumption of a high glucosinolate diet is linked with reduced incidence of chronic diseases, future large-scale placebo-controlled human trials including standardized glucosinolate supplements are needed.
Risk for Cardiovascular Disease and One-Year Mortality in Patients With Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea Syndrome Overlap Syndrome
Authors: Tang Manyun , Wang Yidan , Wang Mengjie , Tong Rui , Shi Tao
Published: October 2021

Background: Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSAS) overlap syndrome (OS) are thought to be at increased risk for cardiovascular diseases.

Objective: To evaluate the burden of cardiovascular diseases and long-term outcomes in patients with OS.

Methods: This was a retrospective cohort study. The prevalence of cardiovascular diseases and 1-year mortality were compared among patients diagnosed with OS (OS group), COPD alone (COPD group) and OSAS alone (OSAS group), and Cox proportional hazards models were used to assess independent risk factors for all-cause mortality.

Results: Overall, patients with OS were at higher risk for pulmonary hypertension (PH), heart failure and all-cause mortality than patients with COPD or OSAS (all p < 0.05). In multivariate Cox regression analysis, the Charlson comorbidity index (CCI) score [adjusted hazard ratio (aHR): 1.273 (1.050–1.543); p = 0.014], hypertension [aHR: 2.006 (1.005–4.004); p = 0.048], pulmonary thromboembolism (PTE) [aHR: 4.774 (1.335–17.079); p = 0.016] and heart failure [aHR: 3.067 (1.521–6.185); p = 0.002] were found to be independent risk factors for 1-year all-cause mortality.

Conclusion: Patients with OS had an increased risk for cardiovascular diseases and 1-year mortality. More efforts are needed to identify the causal relationship between OS and cardiovascular diseases, promoting risk stratification and the management of these patients.
Cystic Fibrosis Transmembrane Conductance Regulator Folding Mutations Reveal Differences in Corrector Efficacy Linked to Increases in Immature Cystic Fibrosis Transmembrane Conductance Regulator Expression
Authors: Peters Kathryn W. , Gong Xiaoyan , Frizzell Raymond A.
Published: October 2021

Background: Most cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that lead to protein misfolding and degradation by the ubiquitin–proteasome system. Previous studies demonstrated that PIAS4 facilitates the modification of wild-type (WT) and F508del CFTR by small ubiquitin-like modifier (SUMO)-1, enhancing CFTR biogenesis by slowing immature CFTR degradation and producing increased immature CFTR band B.

Methods: We evaluated two correction strategies using misfolding mutants, including the common variant, F508del. We examined the effects on mutant expression of co-expression with PIAS4 (E3 SUMO ligase), and/or the corrector, C18. To study the impact of these correction conditions, we transfected CFBE410- cells, a bronchial epithelial cell line, with a CFTR mutant plus: (1) empty vector, (2) empty vector plus overnight 5 μM C18, (3) PIAS4, and (4) PIAS4 plus C18. We assessed expression at steady state by immunoblot of CFTR band B, and if present, band C, and the corresponding C:B band ratio. The large PIAS4-induced increase in band B expression allowed us to ask whether C18 could act on the now abundant immature protein to enhance correction above the control level, as reported by the C:B ratio.

Results: The data fell into three mutant CFTR categories as follows: (1) intransigent: no observable band C under any condition (i.e., C:B = 0); (2) throughput responsive: a C:B ratio less than control, but suggesting that the increased band C resulted from PIAS4-induced increases in band B production; and (3) folding responsive: a C:B ratio greater than control, reflecting C18-induced folding greater than that expected from increased throughput due to the PIAS4-induced band B level.

Conclusion: These results suggest that the immature forms of CFTR folding intermediates occupy different loci within the energetic/kinetic folding landscape of CFTR. The evaluation of their properties could assist in the development of correctors that can target the more difficult-to-fold mutant conformations that occupy different sites within the CFTR folding pathway.
Amelioration of Ambient Particulate Matter (PM2.5)-Induced Lung Injury in Rats by Aerobic Exercise Training
Authors: Qin Fei , Fan Zhengzheng , Xu Minxiao , Wang Zhongwei , Dong Yanan , Qu Chaoyi , Cui Shuqiang , Zhao Lina , Zhao Jiexiu
Published: October 2021

Ambient particulate matter (PM2.5), as an inflammation-inducing factor, increases the prevalence of lung injury. The aim of this study was to examine the protective effect and mechanism of aerobic exercise on PM2.5 exposure-induced lung injury. Forty Wistar rats were randomly divided into four groups: sedentary+PM2.5 exposure, exercise+PM2.5 exposure, sedentary, and exercise groups. All rats in the exercise-related groups underwent 8-week aerobic interval treadmill training (5daysweek−1, 1hday−1). PM-exposed rats were exposed to ambient PM2.5 (6h day−1) for 3weeks after the 8-week exercise intervention. Then, ventilation function, histopathological changes, and inflammation responses of pulmonary tissue were examined. Results showed that PM2.5 exposure induced lung injury as manifested by decreased pulmonary function, abnormal histopathological changes, and increased pro-inflammatory cytokine levels (tumor necrosis factor-α and Interleukin-1α). Aerobic exercise alleviated the airway obstruction, reduced respiratory muscle strength, bronchial mucosal exfoliation, ultrastructure damage, and inflammatory responses induced by PM2.5 in exercise-related groups. The benefits of exercise were related with the downregulation of p38-mitogen-activated protein kinase (MAPK), and the subsequent inhibition of the pathways of the cyclooxygenase 2 (COX-2) product, prostaglandin E2 (PGE2). Thus, pre-exercise training may be an effective way to protect against PM2.5-induced lung inflammatory injury in rats.
Properties and Differential Expression of H+ Receptors in Dorsal Root Ganglia: Is a Labeled-Line Coding for Acid Nociception Possible?
Authors: Páez Omar , Segura-Chama Pedro , Almanza Angélica , Pellicer Francisco , Mercado Francisco
Published: October 2021

Pain by chemical irritants is one of the less well-described aspects of nociception. The acidic substance is the paradigm of the chemical noxious compound. An acidic insult on cutaneous, subcutaneous and muscle tissue results in pain sensation. Acid (or H+) has at least two main receptor channels in dorsal root ganglia (DRG) nociceptors: the heat receptor transient receptor potential vanilloid 1 (TRPV1) and the acid-sensing ionic channels (ASICs). TRPV1 is a low-sensitivity H+receptor, whereas ASIC channels display a higher H+sensitivity of at least one order of magnitude. In this review, we first describe the functional and structural characteristics of these and other H+-receptor candidates and the biophysics of their responses to low pH. Additionally, we compile reports of the expression of these H+-receptors (and other possible complementary proteins) within the DRG and compare these data with mRNA expression profiles from single-cell sequencing datasets for ASIC3, ASIC1, transient receptor potential Ankiryn subtype 1 (TRPA1) and TRPV1. We show that few nociceptor subpopulations (discriminated by unbiased classifications) combine acid-sensitive channels. This comparative review is presented in light of the accumulating evidence for labeled-line coding for most noxious sensory stimuli.
Atrial Flutter Mechanism Detection Using Directed Network Mapping
Authors: Vila Muhamed , Rivolta Massimo Walter , Luongo Giorgio , Unger Laura Anna , Luik Armin , Gigli Lorenzo , Lombardi Federico , Loewe Axel , Sassi Roberto
Published: October 2021

Atrial flutter (AFL) is a common atrial arrhythmia typically characterized by electrical activity propagating around specific anatomical regions. It is usually treated with catheter ablation. However, the identification of rotational activities is not straightforward, and requires an intense effort during the first phase of the electrophysiological (EP) study, i.e., the mapping phase, in which an anatomical 3D model is built and electrograms (EGMs) are recorded. In this study, we modeled the electrical propagation pattern of AFL (measured during mapping) using network theory (NT), a well-known field of research from the computer science domain. The main advantage of NT is the large number of available algorithms that can efficiently analyze the network. Using directed network mapping, we employed a cycle-finding algorithm to detect all cycles in the network, resembling the main propagation pattern of AFL. The method was tested on two subjects in sinus rhythm, six in an experimental model ofin-silicosimulations, and 10 subjects diagnosed with AFL who underwent a catheter ablation. The algorithm correctly detected the electrical propagation of both sinus rhythm cases andin-silicosimulations. Regarding the AFL cases, arrhythmia mechanisms were either totally or partially identified in most of the cases (8 out of 10), i.e., cycles around the mitral valve, tricuspid valve and figure-of-eight reentries. The other two cases presented a poor mapping quality or a major complexity related to previous ablations, large areas of fibrotic tissue, etc. Directed network mapping represents an innovative tool that showed promising results in identifying AFL mechanisms in an automatic fashion. Further investigations are needed to assess the reliability of the method in different clinical scenarios.
Contraction-Induced Loss of Plasmalemmal Electrophysiological Function Is Dependent on the Dystrophin Glycoprotein Complex
Authors: Baumann Cory W. , Lindsay Angus , Sidky Sylvia R. , Ervasti James M. , Warren Gordon L. , Lowe Dawn A.
Published: October 2021

Weakness and atrophy are key features of Duchenne muscular dystrophy (DMD). Dystrophin is one of the many proteins within the dystrophin glycoprotein complex (DGC) that maintains plasmalemmal integrity and cellular homeostasis. The dystrophin-deficient mdx mouse is also predisposed to weakness, particularly when subjected to eccentric (ECC) contractions due to electrophysiological dysfunction of the plasmalemma. Here, we determined if maintenance of plasmalemmal excitability during and after a bout of ECC contractions is dependent on intact and functional DGCs rather than, solely, dystrophin expression. Wild-type (WT) and dystrophic mice (mdx, mL172H and Sgcb−/− mimicking Duchenne, Becker and Limb-girdle Type 2E muscular dystrophies, respectively) with varying levels of dystrophin and DGC functionality performed 50 maximal ECC contractions with simultaneous torque and electromyographic measurements (M-wave root-mean-square, M-wave RMS). ECC contractions caused all mouse lines to lose torque (p<0.001); however, deficits were greater in dystrophic mouse lines compared to WT mice (p<0.001). Loss of ECC torque did not correspond to a reduction in M-wave RMS in WT mice (p=0.080), while deficits in M-wave RMS exceeded 50% in all dystrophic mouse lines (p≤0.007). Moreover, reductions in ECC torque and M-wave RMS were greater in mdx mice compared to mL172H mice (p≤0.042). No differences were observed between mdx and Sgcb−/− mice (p≥0.337). Regression analysis revealed ≥98% of the variance in ECC torque loss could be explained by the variance in M-wave RMS in dystrophic mouse lines (p<0.001) but not within WT mice (R2=0.211; p=0.155). By comparing mouse lines that had varying amounts and functionality of dystrophin and other DGC proteins, we observed that (1) when all DGCs are intact, plasmalemmal action potential generation and conduction is maintained, (2) deficiency of the DGC protein β-sarcoglycan is as disruptive to plasmalemmal excitability as is dystrophin deficiency and, (3) some functionally intact DGCs are better than none. Our results highlight the significant role of the DGC plays in maintaining plasmalemmal excitability and that a collective synergism (via each DGC protein) is required for this complex to function properly during ECC contractions.
Prefrontal Cortex Oxygenation During Endurance Performance: A Systematic Review of Functional Near-Infrared Spectroscopy Studies
Authors: De Wachter Jonas , Proost Matthias , Habay Jelle , Verstraelen Matthias , Díaz-García Jesús , Hurst Philip , Meeusen Romain , Van Cutsem Jeroen , Roelands Bart
Published: October 2021

Introduction: A myriad of factors underlie pacing-/exhaustion-decisions that are made during whole-body endurance performance. The prefrontal cortex (PFC) is a brain region that is crucial for decision-making, planning, and attention. PFC oxygenation seems to be a mediating factor of performance decisions during endurance performance. Nowadays, there is no general overview summarizing the current knowledge on how PFC oxygenation evolves during whole-body endurance performance and whether this is a determining factor.

Methods: Three electronic databases were searched for studies related to the assessment of PFC oxygenation, through near-IR spectroscopy (NIRS), during endurance exercise. To express PFC oxygenation, oxygenated (HbO2) and deoxygenated hemoglobin (HHb) concentrations were the primary outcome measures.

Results: Twenty-eight articles were included. Ten articles focused on assessing prefrontal oxygenation through a maximal incremental test (MIT) and 18 focused on using endurance tasks at workloads ranging from low intensity to supramaximal intensity. In four MIT studies measuring HbO2, an increase of HbO2 was noticed at the respiratory compensation point (RCP), after which it decreased. HbO2 reached a steady state in the four studies and increased in one study until exhaustion. All studies found a decrease or steady state in HHb from the start until RCP and an increase to exhaustion. In regard to (non-incremental) endurance tasks, a general increase in PFC oxygenation was found while achieving a steady state at vigorous intensities. PCF deoxygenation was evident for near-to-maximal intensities at which an increase in oxygenation and the maintenance of a steady state could not be retained.

Discussion/Conclusion: MIT studies show the presence of a cerebral oxygenation threshold (ThCox) at RCP. PFC oxygenation increases until the RCP threshold, thereafter, a steady state is reached and HbO2 declines. This study shows that the results obtained from MIT are transferable to non-incremental endurance exercise. HbO2 increases during low-intensity and moderate-intensity until vigorous-intensity exercise, and it reaches a steady state in vigorous-intensity exercise. Furthermore, ThCox can be found between vigorous and near-maximal intensities. During endurance exercise at near-maximal intensities, PFC oxygenation increases until the value exceeding this threshold, resulting in a decrease in PFC oxygenation. Future research should aim at maintaining and improving PFC oxygenation to help in improving endurance performance and to examine whether PFC oxygenation has a role in other performance-limiting factors.
The ARRE RING-Type E3 Ubiquitin Ligase Negatively Regulates Cuticular Wax Biosynthesis in Arabidopsis thaliana by Controlling ECERIFERUM1 and ECERIFERUM3 Protein Levels
Authors: Liu Shuang , Tong Meixuezi , Zhao Lifang , Li Xin , Kunst Ljerka
Published: October 2021

The outer epidermal cell walls of plant shoots are covered with a cuticle, a continuous lipid structure that provides protection from desiccation, UV light, pathogens, and insects. The cuticle is mostly composed of cutin and cuticular wax. Cuticular wax synthesis is synchronized with surface area expansion during plant development and is associated with plant responses to biotic and abiotic stresses. Cuticular wax deposition is tightly regulated by well-established transcriptional and post-transcriptional regulatory mechanisms, as well as post-translationally via the ubiquitin-26S proteasome system (UPS). The UPS is highly conserved in eukaryotes and involves the covalent attachment of polyubiquitin chains to the target protein by an E3 ligase, followed by the degradation of the modified protein by the 26S proteasome. A large number of E3 ligases are encoded in the Arabidopsis genome, but only a few have been implicated in the regulation of cuticular wax deposition. In this study, we have conducted an E3 ligase reverse genetic screen and identified a novel RING-type E3 ubiquitin ligase, AtARRE, which negatively regulates wax biosynthesis in Arabidopsis. Arabidopsis plants overexpressing AtARRE exhibit glossy stems and siliques, reduced fertility and fusion between aerial organs. Wax load and wax compositional analyses of AtARRE overexpressors showed that the alkane-forming branch of the wax biosynthetic pathway is affected. Co-expression of AtARRE and candidate target proteins involved in alkane formation in both Nicotiana benthamiana and stable Arabidopsis transgenic lines demonstrated that AtARRE controls the levels of wax biosynthetic enzymes ECERIFERUM1 (CER1) and ECERIFERUM3 (CER3). CER1 has also been confirmed to be a ubiquitination substrate of the AtARRE E3 ligase by an in vivo ubiquitination assay using a reconstituted Escherichia coli system. The AtARRE gene is expressed throughout the plant, with the highest expression detected in fully expanded rosette leaves and oldest stem internodes. AtARRE gene expression can also be induced by exposure to pathogens. These findings reveal that wax biosynthesis in mature plant tissues and in response to pathogen infection is controlled post-translationally.
Genetic Modification of KNAT7 Transcription Factor Expression Enhances Saccharification and Reduces Recalcitrance of Woody Biomass in Poplars
Authors: Ahlawat Yogesh Kumar , Nookaraju Akula , Harman-Ware Anne E. , Doeppke Crissa , Biswal Ajaya K. , Joshi Chandrashekhar P.
Published: October 2021

The precise role of KNAT7 transcription factors (TFs) in regulating secondary cell wall (SCW) biosynthesis in poplars has remained unknown, while our understanding of KNAT7 functions in other plants is continuously evolving. To study the impact of genetic modifications of homologous and heterologous KNAT7 gene expression on SCW formation in transgenic poplars, we prepared poplar KNAT7 (PtKNAT7) overexpression (PtKNAT7-OE) and antisense suppression (PtKNAT7-AS) vector constructs for the generation of transgenic poplar lines via Agrobacterium-mediated transformation. Since the overexpression of homologous genes can sometimes result in co-suppression, we also overexpressed Arabidopsis KNAT7 (AtKNAT7-OE) in transgenic poplars. In all these constructs, the expression of KNAT7 transgenes was driven by developing xylem (DX)-specific promoter, DX15. Compared to wild-type (WT) controls, many SCW biosynthesis genes downstream of KNAT7 were highly expressed in poplar PtKNAT7-OE and AtKNAT7-OE lines. Yet, no significant increase in lignin content of woody biomass of these transgenic lines was observed. PtKNAT7-AS lines, however, showed reduced expression of many SCW biosynthesis genes downstream of KNAT7 accompanied by a reduction in lignin content of wood compared to WT controls. Syringyl to Guaiacyl lignin (S/G) ratios were significantly increased in all three KNAT7 knockdown and overexpression transgenic lines than WT controls. These transgenic lines were essentially indistinguishable from WT controls in terms of their growth phenotype. Saccharification efficiency of woody biomass was significantly increased in all transgenic lines than WT controls. Overall, our results demonstrated that developing xylem-specific alteration of KNAT7 expression affects the expression of SCW biosynthesis genes, impacting at least the lignification process and improving saccharification efficiency, hence providing one of the powerful tools for improving bioethanol production from woody biomass of bioenergy crops and trees.
The Influence of COVID-19 on Irrational Consumption Behavior in a Chinese Sample: Based on a Serial Mediating Model
Authors: Yue-Qian Hu , Piao Xie , Ying Wang , Zhi-Xin Huang , Yi-Ting Wu , Hai-Long Sun
Published: October 2021

Based on the scarcity theory, this study focuses on exploring the relationship between the severity of public health emergencies (i.e., COVID-19) and individual irrational consumer behaviors through the serial mediating variables of perceived scarcity (PS) and negative mentality (NM). An online questionnaire was used to collect data from participants in China and we obtained 466 effective (115 male and 351 female) questionnaires in total. The findings showed that the relationship between each pair of factors – perceived pandemic severity, PS, NM, and irrational consumption behaviors – was significantly positive. Although the perception of the severity of this public health emergency did not directly predict irrational consumer behavior, the effect was mediated by PS and NM independently and serially. These findings reveal that people who strongly perceive scarcity and are prone to negative attitudes are more likely to demonstrate irrational consumer behaviors (such as rushing to buy and hoard living supplies) once the public perceives a public health emergency as severe. This effect occurs because the PS that results from the epidemic affects people’s cognition, emotion, and behavior.
Can Masked Emotion-Laden Words Prime Emotion-Label Words? An ERP Test on the Mediated Account
Authors: Wu Chenggang , Zhang Juan , Yuan Zhen
Published: October 2021

The present event-related potential (ERP) study explored whether masked emotion-laden words could facilitate the processing of both emotion-label words and emotion-laden words in a valence judgment task. The results revealed that emotion-laden words as primes failed to influence target emotion-label word processing, whereas emotion-laden words facilitated target emotion-laden words in the congruent condition. Specifically, decreased late positivity complex (LPC) was elicited by emotion-laden words primed by emotion-laden words of the same valence than those primed by emotion-laden words of different valence. Nevertheless, no difference was observed for emotion-label words as targets. These findings supported the mediated account that claimed emotion-laden words engendered emotion via the mediation of emotion-label words and hypothesized that emotion-laden words could not prime emotion-label words in the masked priming paradigm. Moreover, this study provided additional evidence showing the distinction between emotion-laden words and emotion-label words.
Evaluating Educational Credentials of Teachers as Predictor of Effective Teaching: A Pupil Fixed-Effect Modeling Approach
Authors: Liu Ji
Published: October 2021

Many factors serve as predictors of effective teaching; particularly, there is an ongoing debate regarding whether the educational credentials of teachers are indicative of their contribution to pupil's educational success. Utilizing pupil fixed-effect modeling and the China Education Panel Survey dataset (n = 5,032), this study evaluates the extent to which teachers who hold at least a Bachelor of Education (BEd) degree perform better than those who do not, in terms of pupil learning gains over the course of a full academic year. Empirical results from the pupil fixed-effect model indicate that mean learning gain is 0.042 SDs (95% CI: 0.008–0.083, p = 0.040) higher among pupils who studied with teachers holding higher educational credentials (at least a BEd degree) than those with lower educational credentials. This effect translates to approximately 1 month of additional learning per year, which is significant considering the potential compounding aggregation effects over the course of the entire educational career of pupils. This study adds new evidence that highlights the importance of the educational credentials of teachers as a predictor of effective teaching and that better-educated teachers can lead to improved pupil learning gains.
Initial Validation and Findings From the Willing/Ready Subscale of the Church Addiction Response Scale
Authors: Clements Andrea D. , Cyphers Natalie , Whittaker Deborah L. , McCarty Brett
Published: October 2021

Addiction has been a global health crisis over recent decades and worsened substantially during COVID-19 lockdowns. We report on the development, validation, and findings from an instrument developed to assess the readiness of churches in the Appalachian Highlands to address addiction. The Church Addiction Response Scale (CARS) is a 41-item, three section measure assessing “What are your views about addiction?” (14 items), “What are your views about interacting with people who are addicted to drugs?” (11 items), and “What do you think the church’s role is in addressing addiction?” (16 items). The CARS was found to be unidimensional with strong internal consistency and initial evidence of construct validity was positive. Most respondents reported willingness to assist people living with addiction, but many reported that they felt underprepared, thus were not ready. Areas of preparation were largely those that could be addressed through training, such as understanding the physiology and psychology of addiction, available treatment options, and how to avoid doing harm. Thus, with adequate training, the likelihood of equipping a church-based workforce to provide support for people living with addiction seems attainable.
Emotional Reactivity and Emotion Regulation Among Young Adults During COVID-19 Lockdown: The Moderating Role of Gender and Engagement in Sports
Authors: Mladenović Marijana , Stojanović Nikola , Stojanović Darko , Živković Mladen , Aleksić Dragana , Tešanović Gorana , Momčilović Vladimir
Published: October 2021

The effects of the COVID-19 pandemic on mental health have not been fully inspected among the young adults’ population. The objectives of the present study were: (1) to examine differences in emotional reactivity and emotion regulation between, both gender and sports engagement level during the first 2 weeks of the lockdown; and (2) to examine the possible impact of emotion regulation on emotional reactivity, and possible significant roles of gender and sports engagement level as moderators. This cross-sectional study included 315 Serbian young adults (aged 18–26 years old) during COVID-19 lockdown. Respondents answered socio-demographic questions and the Serbian version of the Multidimensional Emotion Questionnaire (MEQ). The results of confirmatory factor analysis indicated good fit for both positive and negative reactivity scales (SRMR = 0.037; CFI = 0.984, RMSEA = 0.046, and SRMR = 0.055; CFI = 0.964, RMSEA = 0.064, respectively). Gender differences were found in both positive (p= 0.039;d= 0.28) and negative emotional reactivity scales (p< 0.001;d= 0.60), with females reported lower and higher values, respectively. Professional athletes presented higher scores in positive reactivity scale in comparison to non-athletes (p< 0.001;d= 0.78) and recreational athletes (p= 0.034;d= 0.34) during 2 weeks of COVID-19 lockdown. Conversely, professional athletes scored lower in negative emotional reactivity scale in comparison to non-athletes (p< 0.001;d= 0.85) and recreational athletes (p= 0.006;d= 0.42). Both gender and sports engagement level differences were found for negative, but not for positive emotion regulation scale. Furthermore, results showed that engagement in sports level plays a significant role as moderator in relationship between negative regulation and negative reactivity, where professional athletes presented significant interaction effect and predicted lower negative reactivity scores compared to non-athletes and recreational athletes. However, gender does not moderate the influence of emotion regulation on emotional reactivity either positive or negative. Engagement in sports as a lifestyle may contribute to better emotional harmony especially in the crisis situation as COVID-19 lockdown.
Effectiveness of Physical Activity Intervention on ADHD Symptoms: A Systematic Review and Meta-Analysis
Authors: Xie Yongtao , Gao Xuping , Song Yiling , Zhu Xiaotong , Chen Mengge , Yang Li , Ren Yuanchun
Published: October 2021

Objective: To assess the effectiveness of physical activity (PA) intervention on attention-deficit/hyperactivity disorder (ADHD)-related symptoms.

Method: Studies that investigated PA intervention for ADHD-related symptoms were identified through searching PubMed, Web of Science, Cochrane Library, and Embase databases from inception through June 2021. Standardized mean difference (SMD) with 95% confidence interval (CI) was used to assess the effectiveness of PA intervention on improving ADHD-related symptoms. The meta-analyses were conducted using fixed-effect or random-effect models according to the heterogeneity of the studies.

Results: Nine before–after studies (232 participants) and 14 two-group control studies (162 participants/141 controls) were included in this meta-analysis. Combined results for before–after studies indicated significant improvements on all studied ADHD-related symptoms (inattention: SMD = 0.604, 95% CI: 0.374–0.834, p < 0.001; hyperactivity/impulsivity: SMD = 0.676, 95% CI: 0.401–0.950, p < 0.001; emotional problems: SMD = 0.416, 95% CI: 0.283–0.549, p < 0.001; behavioral problems: SMD = 0.347, 95% CI: 0.202–0.492, p < 0.001). Meta-analyses for two-group control studies further confirmed that PA intervention significantly improved the inattentive symptom (SMD = 0.715, 95% CI: 0.105, 1.325, p = 0.022). Subgroup analyses suggested significant beneficial effect on inattention symptoms in children. Moreover, closed motor skills were beneficial for hyperactive/impulsive problems (SMD = 0.671, p < 0.001), while open motor skills were beneficial for attention problems (SMD = 0.455, p = 0.049). When excluding studies with combined medication, the studies in unmedicated participants in before–after studies still showed significant results in all studied ADHD-related symptoms as in the overall analysis. Given the limited sample size, the best frequency and intensity of PA intervention need further investigation.

Conclusion: Our results suggested that PA intervention could possibly improve ADHD-related symptoms, especially inattention symptoms. Closed-skill and open-skill activities could be beneficial for hyperactivity/impulsivity and inattention symptoms, respectively. Further high-quality randomized clinical trials with large sample size are needed.