Frontiers in Physiology最新文献

[This retracts the article DOI: 10.3389/fphys.2020.00829.].

Introduction: Aedes aegypti, the vector of multiple arboviral diseases, is a prime health concern worldwide. The surge in Aedes-borne diseases emphasizes the urgent need for efficient vector control measures. Synthetic pesticides used traditionally, however, present environmental concerns and issues like resistance development, causing the use of higher chemical doses. Hence, alternate interventions like the use of insect growth regulators (diflubenzuron; DFB) show promise because of their unique mechanism of action and environmental safety. Nevertheless, mosquitoes have the potential to develop resistance to any chemical. Thus, the present study investigates the use of DFB in combination with verapamil (DFB-V; 1:10) as a possible mosquito intervention measure.

Methods: The effects of both DFB and DFB-V were assessed on the larval development, adult emergence and expression of detoxification enzymes, non-specific esterases, glutathione S-transferase (GST), acetylcholinesterase (AChE), and monooxygenases in laboratory-reared (AND-Ae. aegypti) and wild-caught (GVD-Ae. aegypti) strains of Ae. aegypti. The effects on the survival of non-target organisms were also investigated.

Results: The investigations showed that DFB-V treatment of the Ae. aegypti fourth instars caused a 1.16-1.37 fold higher adult emergence suppression than DFB alone, reducing the IE₅₀ values. The DFB treatment increased β-esterases, AChE, and monooxygenases but reduced the GST and α-esterase levels. The effects enhanced with the use of DFB-V, causing a significant decrease in α-esterase (7.7-fold) and an increase in monooxygenases (7.8-fold) (p < 0.05) in AND-Ae. aegypti compared to the wild-caught strain. The variation in enzyme levels in the two strains may be due to the stress caused by insecticides of different chemical natures used in the fields. No negative effects were observed on the non-target organisms-Gambusia affinis, Mesocyclops thermocyclopoides, and Paramecium tetraurelia.

Conclusion: The studies showed the growth regulatory efficacy of DFB and probable role of GST and α-esterases in increasing the effects of DFB when synergized with verapamil. Further, the DFB-V combination did not result in any significant negative effects on the non-target organisms ascertaining its safe use. This is the first report unraveling the effects of the DFB-verapamil combination on the defense mechanism of Ae. aegypti. Further studies may assist in developing focused and eco-safe plans for managing Ae. aegypti populations effectively.

Eccentric training has been proposed as a potential method for enhancing athletes' movement speed. However, a systematic review specifically examining the impact of eccentric training on movement speed in athletes has yet to be conducted. This paper aims to fill this gap by evaluating the effects of eccentric training on movement speed in athletes.A systematic search was carried out on May 15, 2024, in accordance with the PRISMA guidelines for systematic reviews and meta-analyses. The search was conducted across multiple databases, including Web of Science, EBSCOhost, PubMed, CNKI, and VIP, using keywords related to eccentric training, athletes, and movement speed. Out of 421 reviews screened, nine met the inclusion criteria. The quality of the studies was assessed using the PEDro scale, with an average score of 3.67 (range 3-4). The results indicated that short-distance sprint speed (n = 7) was the most affected by eccentric training interventions. Sport-specific movement speed (n = 3) and change of direction speed (COD) (n = 5) were also positively influenced, although to a lesser extent.In conclusion, eccentric training significantly enhances sport-specific movement speed and COD speed, with more moderate effects on short-distance sprinting. These findings suggest that eccentric training can be a valuable intervention for improving movement speed in athletes, especially for sports that involve rapid directional changes.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024547112, identifier CRD42024547112.

Introduction: This study aimed to develop a deep learning-based method for interpreting magnetic resonance imaging (MRI) scans of temporomandibular joint (TMJ) anterior disc displacement (ADD) and to formulate an automated diagnostic system for clinical practice.

Methods: The deep learning models were utilized to identify regions of interest (ROI), segment TMJ structures including the articular disc, condyle, glenoid fossa, and articular tubercle, and classify TMJ ADD. The models employed Grad-CAM heatmaps and segmentation annotation diagrams for visual diagnostic predictions and were deployed for clinical application. We constructed four deep-learning models based on the ResNet101_vd framework utilizing an MRI dataset of 618 TMJ cases collected from two hospitals (Hospitals SS and SG) and a dataset of 840 TMJ MRI scans from October 2022 to July 2023. The training and validation datasets included 700 images from Hospital SS, which were used to develop the models. Model performance was assessed using 140 images from Hospital SS (internal validity test) and 140 images from Hospital SG (external validity test). The first model identified the ROI, the second automated the segmentation of anatomical components, and the third and fourth models performed classification tasks based on segmentation and non-segmentation approaches. MRI images were classified into four categories: normal (closed mouth), ADD (closed mouth), normal (open mouth), and ADD (open mouth). Combined findings from open and closed-mouth positions provided conclusive diagnoses. Data augmentation techniques were used to prevent overfitting and enhance model robustness. The models were assessed using performance metrics such as precision, recall, mean average precision (mAP), F1-score, Matthews Correlation Coefficient (MCC), and confusion matrix analysis.

Results: Despite lower performance with Hospital SG's data than Hospital SS's, both achieved satisfactory results. Classification models demonstrated high precision rates above 92%, with the segmentation-based model outperforming the non-segmentation model in overall and category-specific metrics.

Discussion: In summary, our deep learning models exhibited high accuracy in detecting TMJ ADD and provided interpretable, visualized predictive results. These models can be integrated with clinical examinations to enhance diagnostic precision.

Introduction: Adrenergic activation of protein kinase A (PKA) in cardiac muscle targets the sarcolemma, sarcoplasmic reticulum, and contractile apparatus to increase contractile force and heart rate. In the thin filaments of the contractile apparatus, cardiac troponin I (cTnI) Ser22 and Ser23 in the cardiac-specific N-terminal peptide (NcTnI: residues 1 to 32) are the targets for PKA phosphorylation. Phosphorylation causes a 2-3 fold decrease of affinity of cTn for Ca²⁺ associated with a higher rate of Ca²⁺ dissociation from cTnC leading to a faster relaxation rate of the cardiac muscle (lusitropy). Cardiomyopathy-linked mutations primarily affect Ca²⁺ regulation or the PKA-dependent modulatory system, such that Ca²⁺-sensitivity becomes independent of phosphorylation level (uncoupling) and this could be sufficient to induce cardiomyopathy. A drug that could restore the phosphorylation-dependent modulation of Ca²⁺-sensitivity could have potential for treatment of these pathologies. We have found that a number of small molecules, including silybin B, resveratrol and EGCG, can restore coupling in single filament assays.

Methods: We did molecular dynamics simulations (5x1500ns for each condition) of the unphosphorylated and phosphorylated cardiac troponin core with the G159D DCM mutation in the presence of the 5 ligands and analysed the effects on several dynamic parameters. We also studied the effect of the ligands on the contractility of cardiac muscle myocytes with ACTC E99K and TNNT2 R92Q mutations in response to dobutamine.

Results: Silybin B, EGCG and resveratrol restored the phosphorylation-induced change in molecular dynamics to wild-type values, whilst silybin A, an inactive isomer of silybin B, and Epicatechin gallate, an EGCG analogue that does not recouple, did not. We analysed the atomic-level changes induced by ligand binding to explain recoupling. Mutations ACTC E99K and TNNT2 R92Q blunt the increased relaxation speed response to β1 adrenergic stimulation of cardiac myocytes and we found that resveratrol, EGCG and silybin B could restore the β1 adrenergic response, whereas silybin A did not.

Discussion: The uncoupling phenomenon caused by cardiomyopathy-related mutations and the ability of small molecules to restore coupling in vitro and lusitropy in myocytes is observed at the cellular, molecular and atomistic levels therefore, restoring lusitropy is a suitable target for treatment. Further research on compounds that restore lusitropy is thus indicated as treatments for genetic cardiomyopathies. Further molecular dynamics simulations could define the specific properties needed for recoupling and allow for the prediction and design of potential new drugs.

Introduction: Cerebral ischemia leads to multiple organ dysfunctions, with the lungs among the most severely affected. Although adverse pulmonary consequences contribute significantly to reduced life expectancy after stroke, the impact of global or focal cerebral ischemia on respiratory mechanical parameters remains poorly understood.

Methods: Rats were randomly assigned to undergo surgery to induce permanent global cerebral ischemia (2VO) or focal cerebral ischemia (MCAO), or to receive a sham operation (SHAM). Three days later, end-expiratory lung volume, airway and respiratory tissue mechanics were measured at positive end-expiratory pressure (PEEP) levels of 0, 3 and 6 cmH₂O. Bronchial responsiveness to methacholine, lung cytokine levels, wet-to-dry ratio, blood gas parameters and cerebral stroke markers were also evaluated.

Results: Global and focal cerebral ischemia had no significant effect on end-expiratory lung volume, bronchial responsiveness, and arterial blood gas levels. No change in respiratory mechanics and inflammatory response was evident after 2VO. Conversely, MCAO decreased airway resistance at PEEP 0, deteriorated respiratory tissue damping and elastance at all PEEP levels, and elevated Hct and Hgb. MCAO also caused lung edema and augmented IL-1β and TNF-α in the lung tissue without affecting IL-6 and IL-8 levels.

Discussion: Our findings suggest that global cerebral ischemia has no major pulmonary consequences. However, deteriorations in the respiratory tissue mechanics develop after permanent focal ischemia due to pulmonary edema formation, hemoconcentration and cytokine production. This respiratory mechanical defect can compromise lung distension at all PEEP levels, which warrants consideration in optimizing mechanical ventilation.

Heart failure with preserved ejection fraction (HFpEF) is a major public health challenge, affecting millions worldwide and placing a significant burden on healthcare systems due to high hospitalization rates and limited treatment options. HFpEF is characterized by impaired cardiac relaxation, or diastolic dysfunction. However, there are no therapies that directly treat the primary feature of the disease. This is due in part to the complexity of normal diastolic function, and the challenge of isolating the mechanisms responsible for dysfunction in HFpEF. Without a clear understanding of the mechanisms driving diastolic dysfunction, progress in treatment development has been slow. In this review, we highlight three key areas of molecular dysregulation directly underlying impaired cardiac relaxation in HFpEF: altered calcium sensitivity in the troponin complex, impaired phosphorylation of myosin-binding protein C (cMyBP-C), and reduced titin compliance. We explore how targeting these pathways can restore normal relaxation, improve diastolic function, and potentially provide new therapeutic strategies for HFpEF treatment. Developing effective HFpEF therapies requires precision targeting to balance systolic and diastolic function, avoiding both upstream non-specificity and downstream rigidity. This review highlights three rational molecular targets with a strong mechanistic basis and potential for therapeutic success.

Regular exercise is widely recognized for its numerous physical and mental benefits, but its effects on male reproductive health are less understood. This review aims to summarize the current evidence on the impact of exercise on male reproduction, including reproductive hormone regulation, spermatogenesis sperm quality, and fertility. Moderate exercise improves sperm quality, increasing count, motility, and morphology, while excessive and severe exercise may have detrimental effects. Exercise positively influences fertility by reducing oxidative stress and enhancing sperm DNA integrity. Regular physical activity regulates reproductive hormones, including testosterone, follicle-stimulating hormone, and luteinizing hormone. Exercise-induced weight management and improved insulin sensitivity also contribute to better reproductive health. In conclusion, exercise has a profound impact on male reproductive health, with moderate physical activity promoting improved hormonal balance, sperm quality, and fertility. However, severe/excessive exercise exerts negative effects. These findings imply that a balanced exercise routine, usually mild to moderate, combined with a healthy lifestyle is essential for optimal male reproductive health. However, once exercise is severe and prolonged, it could impair male reproductive health. Further research is needed to understand the mechanisms underlying the exercise-reproduction relationship fully.

Rapid, ultradian biological rhythms are only partly comparable to circadian (24-h) rhythms. Often, the ensuing expectations from this comparison are that 1) ultradian rhythms should be driven by discrete oscillators, 2) they are biochemically buffered, and 3) they must be functionally linked to extrinsic events and cycles. These three expectations are not always met, but perhaps there is an adaptive benefit to ultradian rhythms not meeting these expectations, which sets them functionally apart from circadian rhythms. In view of the extensive descriptions of the manifold types of ultradian rhythms across all biological levels (e.g., see papers in this research topic), it seems important to ask whether we should actively create a new set of definitions and expectations. To make a start, we here lay out some important questions we need to ask about ultradian rhythms. We then illustrate how these questions highlight one key area of exploration: the linked expression of ultradian rhythms in metabolism and behaviour and the role this plays in addressing a negative energy balance.