Effect of inspiratory muscle training in children with asthma: a systematic review and meta-analysis of randomized controlled trials.

Background: Asthma is a common chronic respiratory disease in children. Alongside pharmacological interventions, inspiratory muscle training (IMT) emerges as a complementary therapeutic approach for asthma management. However, the extent of its efficacy in pediatric populations remains uncertain when compared to its benefits in adults. This systematic review aims to evaluate the effectiveness of IMT with threshold loading in children with asthma. Methods: Randomized controlled trials (RCTs) evaluating the efficacy of inspiratory muscle training in pediatric asthma patients were identified through June 2023 across various literature databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAL), Web of Science, China Knowledge Resource Integrated Database (CNKI), Wei Pu Database, Wan Fang Database, and Chinese Biomedical Database (CBM). These trials compared inspiratory muscle training against sham inspiratory muscle training and conventional care. Eligible studies were assessed in terms of risk of bias and quality of evidence. Where feasible, data were pooled and subjected to meta-analysis, with results reported as mean differences (MDs) and 95% confidence intervals (CIs). Results: Six trials involving 333 patients were included in the analysis. IMT demonstrated significant improvements in maximum inspiratory pressure (MIP) (MD 25.36, 95% CI 2.47-48.26, P = 0.03), maximum expiratory pressure (MEP) (MD 14.72, 95% CI 4.21-25.24, P = 0.006), forced vital capacity in percent predicted values [FVC(% pred)] (MD 3.90, 95% CI 1.86-5.93, P = 0.0002), forced expiratory volume in the first second in percent predicted values [FEV1(% pred)] (MD 4.96, 95% CI 2.60-7.32, P < 0.0001), ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) (MD 4.94, 95% CI 2.66-7.21, P < 0.0001), and asthma control test (ACT) (MD = 1.86, 95% CI: 0.96-2.75, P < 0.0001). Conclusions: Findings from randomized controlled trials indicate that inspiratory muscle training enhances respiratory muscle strength and pulmonary function in pediatric asthma patients. Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023449918, identifier: CRD42023449918.

Insights into the Roles of Natural Killer Cells in Osteoarthritis.

Osteoarthritis (OA) is now widely acknowledged as a low-grade inflammatory condition, in which the intrinsic immune system plays a significant role in its pathogenesis. While the involvement of macrophages and T cells in the development of OA has been extensively reviewed, recent research has provided mounting evidence supporting the crucial contribution of NK cells in both the initiation and advancement of OA. Accumulated evidence has emerged in recent years indicating that NK cells play a critical role in OA development and progression. This review will outline the ongoing understanding of the utility of NK cells in the etiology of OA, focusing on how NK cells interact with chondrocytes, synoviocytes, osteoclasts, and other immune cells to influence the course of OA disease.

Effects of long-term closed and socially isolating spaceflight analog environment on default mode network connectivity as indicated by fMRI.

Long-term manned spaceflight and extraterrestrial planet settlement become the focus of space powers. However, the potential influence of closed and socially isolating spaceflight on the brain function remains unclear. A 180-day controlled ecological life support system integrated experiment was conducted, establishing a spaceflight analog environment to explore the effect of long-term socially isolating living. Three crewmembers were enrolled and underwent resting-state fMRI scanning before and after the experiment. We performed both seed-based and network-based analyses to investigate the functional connectivity (FC) changes of the default mode network (DMN), considering its key role in multiple higher-order cognitive functions. Compared with normal controls, the leader of crewmembers exhibited significantly reduced within-DMN and between-DMN FC after the experiment, while two others exhibited opposite trends. Moreover, individual differences of FC changes were further supported by evidence from behavioral analyses. The findings may shed new light on the development of psychological protection for space exploration.

Evaluating serum CXCL12, sCD22, Lp-PLA2 levels and ratios as biomarkers for diagnosis of Alzheimer's disease.

BACKGROUND: Grasping the underlying mechanisms of Alzheimer's disease (AD) is still a work in progress, and existing diagnostic techniques encounter various obstacles. Therefore, the discovery of dependable biomarkers is essential for early detection, tracking the disease's advancement, and steering treatment strategies. AIM: To explore the diagnostic potential of serum CXCL12, sCD22, Lp-PLA2, and their ratios in AD, aiming to enhance early detection and inform targeted treatment strategies. METHODS: The study was conducted in Dongying people's Hospital from January 2021 to December 2022. Participants included 60 AD patients (AD group) and 60 healthy people (control group). Using a prospective case-control design, the levels of CXCL12, sCD22 and Lp-PLA2 and their ratios were detected by enzyme-linked immunosorbent assay kit in the diagnosis of AD. The differences between the two groups were analyzed by statistical methods, and the corresponding ratio was constructed to improve the specificity and sensitivity of diagnosis. RESULTS: Serum CXCL12 levels were higher in the AD group (47.2 ± 8.5 ng/mL) than the control group (32.8 ± 5.7 ng/mL, P < 0.001), while sCD22 levels were lower (14.3 ± 2.1 ng/mL vs 18.9 ± 3.4 ng/mL, P < 0.01). Lp-PLA2 levels were also higher in the AD group (112.5 ± 20.6 ng/mL vs 89.7 ± 15.2 ng/mL, P < 0.05). Significant differences were noted in CXCL12/sCD22 (3.3 vs 1.7, P < 0.001) and Lp-PLA2/sCD22 ratios (8.0 vs 5.2, P < 0.05) between the groups. Receiver operating characteristic analysis confirmed high sensitivity and specificity of these markers and their ratios in distinguishing AD, with area under the curves ranging from 0.568 to 0.787. CONCLUSION: Serum CXCL12 and Lp-PLA2 levels were significantly increased, while sCD22 were significantly decreased, as well as increases in the ratios of CXCL12/sCD22 and Lp-PLA2/sCD22, are closely related to the onset of AD. These biomarkers and their ratios can be used as potential diagnostic indicators for AD, providing an important clinical reference for early intervention and treatment.

Comparison of seven anthropometric indexes to predict hypertension plus hyperuricemia among U.S. adults.

Purpose: This study aims to compare the association of hypertension plus hyperuricemia (HTN-HUA) with seven anthropometric indexes. These include the atherogenic index of plasma (AIP), lipid accumulation product (LAP), visceral adiposity index (VAI), triglyceride-glucose index (TyG), body roundness index (BRI), a body shape index (ABSI), and the cardiometabolic index (CMI). Methods: Data was procured from the National Health and Nutrition Examination Survey (NHANES), which recruited a representative population aged 18 years and above to calculate these seven indexes. Logistic regression analysis was employed to delineate their correlation and to compute the odds ratios (OR). Concurrently, receiver operating characteristic (ROC) curves were utilized to evaluate the predictive power of the seven indexes. Results: A total of 23,478 subjects were included in the study. Among these, 6,537 (27.84%) were patients with HUA alone, 2,015 (8.58%) had HTN alone, and 2,836 (12.08%) had HTN-HUA. The multivariate logistic regression analysis showed that the AIP, LAP, VAI, TyG, BRI, ABSI, and CMI were all significantly associated with concurrent HTN-HUA. The OR for the highest quartile of the seven indexes for HTN-HUA were as follows: AIP was 4.45 (95% CI 3.82-5.18), LAP was 9.52 (95% CI 7.82-11.59), VAI was 4.53 (95% CI 38.9-5.28), TyG was 4.91 (95% CI 4.15-5.80), BRI was 9.08 (95% CI 7.45-11.07), ABSI was 1.71 (95% CI 1.45 -2.02), and CMI was 6.57 (95% CI 5.56-7.76). Notably, LAP and BRI demonstrated significant discriminatory abilities for HTN-HUA, with area under the curve (AUC) values of 0.72 (95% CI 0.71 - 0.73) and 0.73 (95% CI 0.72 - 0.74) respectively. Conclusion: The AIP, LAP, VAI, TyG, BRI, ABSI, and CMI all show significant correlation with HTN-HUA. Notably, both LAP and BRI demonstrate the capability to differentiate cases of HTN-HUA. Among these, BRI is underscored for its effective, non-invasive nature in predicting HTN-HUA, making it a superior choice for early detection and management strategies.

The Association between CYP2C19 Genetic Polymorphism and Prognosis in Patients Receiving Endovascular Therapy.

Background: Potentially substantial impacts on the prognosis have been observed in individuals undergoing endovascular treatment due to cytochrome P450 2c19 (CYP2C19) polymorphism. In an attempt to improve prognosis and lower the recurrence rate, this study investigated the CYP2C19 polymorphism in acute ischemic stroke patients. Materials and Methods: A retrospective analysis was performed on 292 patients with cerebral infarction who had acute endovascular recanalization at the Department of Neurology of Chongqing Hospital of Traditional Chinese Medicine between May 2017 and 2019. The patients were categorized into rapid-, medium-, and slow-metabolism groups based on CYP2C19 gene polymorphism, and their prognosis was monitored. In addition, the prognosis of 188 patients selectively receiving carotid artery stenting at a selected time was also observed. Results: Among the 292 cerebral infarction cases receiving acute endovascular recanalization, the patients in the CYP2C19 rapid-metabolism group regularly took clopidogrel and aspirin combined with antiplatelet therapy and suffered from reoccurrence of apoplexy and cerebral hemorrhage; the 90-day good prognosis had a statistical difference (P < 0.05, prognostic assessment includes hospitalization and 6 months after discharge) and the other adverse events had no statistical difference (including mortality). The 188 patients selectively receiving carotid artery stenting had a recurrence of apoplexy, cerebral hemorrhage, and restenosis rate with a statistical difference (P < 0.05), and the other adverse events had no statistical difference. Conclusions: In conclusion, the findings of the current study indicate that irrespective of whether patients are undergoing selective carotid artery stenting or acute endovascular recanalization, those with rapid CYP2C19 metabolism have a significantly lower likelihood of experiencing adverse prognostic events compared to those with intermediate and slow metabolism. Furthermore, this group also has a more favorable prognosis than the other two groups.

Comparative efficacy of anthropometric indices in predicting 10-year ASCVD risk: insights from NHANES data.

Background: Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide. Accurately predicting the 10-year risk of Atherosclerotic Cardiovascular Disease (ASCVD) is crucial for timely intervention and management. This study aimed to evaluate the predictive performance of six anthropometric indices in assessing the 10-year ASCVD risk. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) database (1999-2018), the study involved 11,863 participants after applying exclusion criteria. Six anthropometric indices-waist circumference (WC), body mass index (BMI), waist-to-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), and waist-to-height0.5 ratio (WHT.5R)-were calculated. The 10-year ASCVD risk was assessed using the 2013 ACC/AHA guidelines & pooled cohort equations model. Participants were divided into two groups based on an ASCVD risk threshold of 7.5%. Statistical analysis included chi-square tests, odds ratios, and receiver operating characteristic (ROC) curves. Results: The study found significant differences in baseline characteristics between participants with ASCVD risk less than 7.5% and those with a risk greater than or equal to 7.5%, stratified by gender. In both male and female groups, individuals with higher ASCVD risk exhibited higher age, waist circumference, BMI, and a higher prevalence of health-compromising behaviors. ABSI emerged as the most accurate predictor of ASCVD risk, with the highest area under the curve (AUC) values in both genders. The optimal cut-off values for ABSI was established for effective risk stratification (cut-off value = 0.08). Conclusion: The study underscores the importance of anthropometric indices, particularly ABSI, in predicting the 10-year risk of ASCVD. These findings suggest that ABSI, along with other indices, can be instrumental in identifying individuals at higher risk for ASCVD, thereby aiding in early intervention and prevention strategies.

Unveiling the Diversity and Modifications of Short Peptides in Buthus martensii Scorpion Venom through Liquid Chromatography-High Resolution Mass Spectrometry.

More recently, short peptides in scorpion venom have received much attention because of their potential for drug discovery. Although various biological effects of these short peptides have been found, their studies have been hindered by the lack of structural information especially in modifications. In this study, small peptides from scorpion venom were investigated using high-performance liquid chromatography high-resolution mass spectrometry followed by de novo sequencing. A total of 156 sequences consisting of 2~12 amino acids were temporarily identified from Buthus martensii scorpion venom. The identified peptides exhibited various post-translational modifications including N-terminal and C-terminal modifications, in which the N-benzoyl modification was first found in scorpion venom. Moreover, a short peptide Bz-ARF-NH2 demonstrated both N-terminal and C-terminal modifications simultaneously, which is extremely rare in natural peptides. In conclusion, this study provides a comprehensive insight into the diversity, modifications, and potential bioactivities of short peptides in scorpion venom.

Sleep deprivation changes frequency-specific functional organization of the resting human brain.

Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies have widely explored the temporal connection changes in the human brain following long-term sleep deprivation (SD). However, the frequency-specific topological properties of sleep-deprived functional networks remain virtually unclear. In this study, thirty-seven healthy male subjects underwent resting-state fMRI during rested wakefulness (RW) and after 36 hours of SD, and we examined frequency-specific spectral connection changes (0.01-0.08 Hz, interval = 0.01 Hz) caused by SD. First, we conducted a multivariate pattern analysis combining linear SVM classifiers with a robust feature selection algorithm, and the results revealed that accuracies of 74.29%-84.29% could be achieved in the classification between RW and SD states in leave-one-out cross-validation at different frequency bands, moreover, the spectral connection at the lowest and highest frequency bands exhibited higher discriminative power. Connection involving the cingulo-opercular network increased most, while connection involving the default-mode network decreased most following SD. Then we performed a graph-theoretic analysis and observed reduced low-frequency modularity and high-frequency global efficiency in the SD state. Moreover, hub regions, which were primarily situated in the cerebellum and the cingulo-opercular network after SD, exhibited high discriminative power in the aforementioned classification consistently. The findings may indicate the frequency-dependent effects of SD on the functional network topology and its efficiency of information exchange, providing new insights into the impact of SD on the human brain.

Long-Term Consumption of 6 Different Beverages and Cardiovascular Disease-Related Mortality: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

The relationship between beverage consumption and risk of cardiovascular disease has been extensively examined in cross-sectional studies. However, limited studies have investigated beverage consumption as a longer-term habitual behavior, which is important owing to potential cumulative harmful or beneficial cardiovascular effects. We examined the association between the long-term consumption of 6 types of beverages (sugar-sweetened or artificially sweetened beverages, tea, coffee, fruit juice, energy drinks, and alcohol) and cardiovascular mortality, by considering sex differences. We conducted a systematic search of MEDLINE, EMBASE, CINAHL, Web of Science, and Scopus databases from 2010 to December 2023. Of 8049 studies identified, 20 studies were included for meta-analysis. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with the use of a random-effects model. We found that long-term coffee consumption was related to reduced cardiovascular disease-related mortality in males (pooled HR: 0.63; 95% CI: 0.46, 0.87; P = 0.005) but not in females (HR: 0.78; 95% CI: 0.60, 1.02; P = 0.07). Long-term higher intake of tea was associated with lower risk of cardiovascular disease-related mortality in all adults (pooled HR: 0.81; 95% CI: 0.72, 0.92; P ≤ 0.001). Higher alcohol intake was linked to higher stroke in both males (pooled HR: 1.44; 95% CI: 1.06, 1.94; P = 0.02) and females (pooled HR: 2.26; 95% CI: 1.34, 3.81; P = 0.002). Higher sugar-sweetened beverage intake was in relation to higher cardiovascular disease-related mortality (pooled HR: 1.31; 95% CI: 1.16, 1.46; P ≤ 0.0001). We concluded that long-term habitual coffee consumption is beneficial for males, and tea consumption is beneficial for all adults. Long-term high alcohol and sugar-sweetened beverage consumption increased risk of cardiovascular disease-related mortality for both males and females. However, we were unable to draw conclusions on the potential benefit or harm of the long-term consumption of fruit juice and energy drinks on cardiovascular disease-related mortality owing to the limited number of studies available. This review was registered at PROSPERO as CRD42020214679.

Decoding the potential role of regulatory T cells in sepsis-induced immunosuppression.

Sepsis, a multiorgan dysfunction with high incidence and mortality, is caused by an imbalanced host-to-infection immune response. Organ-support therapy improves the early survival rate of sepsis patients. In the long term, those who survive the "cytokine storm" and its secondary damage usually show higher susceptibility to secondary infections and sepsis-induced immunosuppression, in which regulatory T cells (Tregs) are evidenced to play an essential role. However, the potential role and mechanism of Tregs in sepsis-induced immunosuppression remains elusive. In this review, we elucidate the role of different functional subpopulations of Tregs during sepsis and then review the mechanism of sepsis-induced immunosuppression from the aspects of regulatory characteristics, epigenetic modification, and immunometabolism of Tregs. Thoroughly understanding how Tregs impact the immune system during sepsis may shed light on preclinical research and help improve the translational value of sepsis immunotherapy.

Frequency-specific segregation and integration of human cerebral cortex: An intrinsic functional atlas.

The cognitive and behavioral functions of the human brain are supported by its frequency multiplexing mechanism. However, there is limited understanding of the dynamics of the functional network topology. This study aims to investigate the frequency-specific topology of the functional human brain using 7T rs-fMRI data. Frequency-specific parcellations were first performed, revealing frequency-dependent dynamics within the frontoparietal control, parietal memory, and visual networks. An intrinsic functional atlas containing 456 parcels was proposed and validated using stereo-EEG. Graph theory analysis suggested that, in addition to the task-positive vs. task-negative organization observed in static networks, there was a cognitive control system additionally from a frequency perspective. The reproducibility and plausibility of the identified hub sets were confirmed through 3T fMRI analysis, and their artificial removal had distinct effects on network topology. These results indicate a more intricate and subtle dynamics of the functional human brain and emphasize the significance of accurate topography.

Cross-talk between Vimentin and autophagy regulates blood-testis barrier disruption induced by cadmium.

The blood-testis barrier (BTB) plays a vital role in mammalian spermatogenesis by separating the seminiferous epithelium into an adluminal and a basal compartment. Cadmium (Cd) is a toxic heavy metal that is widely present in the environment. We observed that Cd can induce BTB disruption, leading to apoptosis of testicular cells. However, the molecular mechanisms contributing to BTB injury induced by Cd have not yet been fully clarified. Vimentin (Vim) is an important desmosome-like junction protein that mediates robust adhesion in the BTB. In this study, we investigated how Vim responds to Cd. We found that Cd treatment led to a significant decrease in Vim expression, accompanied by a marked increase in LC3-II expression and a higer number of autophagosomes. Interestingly, we also observed that Cd-induced autophagy was associated with decreased Vim activity and enhanced apoptosis of testicular cells. To further investigate the role of autophagy in Vim regulation under Cd exposure, we treated cells with an autophagy inhibitor called 3-MA. We found that 3-MA treatment enhanced Vim expression and improved the disruption of the BTB under Cd exposure. Additionally, the inhibition of Vim confirmed the role of autophagy in modulating Vim expression. These results reveal a previously unknown regulatory mechanism of Cd involving the interplay between a heavy metal and a protein.

Multimodal Action Quality Assessment.

Action quality assessment (AQA) is to assess how well an action is performed. Previous works perform modelling by only the use of visual information, ignoring audio information. We argue that although AQA is highly dependent on visual information, the audio is useful complementary information for improving the score regression accuracy, especially for sports with background music, such as figure skating and rhythmic gymnastics. To leverage multimodal information for AQA, i.e., RGB, optical flow and audio information, we propose a Progressive Adaptive Multimodal Fusion Network (PAMFN) that separately models modality-specific information and mixed-modality information. Our model consists of with three modality-specific branches that independently explore modality-specific information and a mixed-modality branch that progressively aggregates the modality-specific information from the modality-specific branches. To build the bridge between modality-specific branches and the mixed-modality branch, three novel modules are proposed. First, a Modality-specific Feature Decoder module is designed to selectively transfer modality-specific information to the mixed-modality branch. Second, when exploring the interaction between modality-specific information, we argue that using an invariant multimodal fusion policy may lead to suboptimal results, so as to take the potential diversity in different parts of an action into consideration. Therefore, an Adaptive Fusion Module is proposed to learn adaptive multimodal fusion policies in different parts of an action. This module consists of several FusionNets for exploring different multimodal fusion strategies and a PolicyNet for deciding which FusionNets are enabled. Third, a module called Cross-modal Feature Decoder is designed to transfer cross-modal features generated by Adaptive Fusion Module to the mixed-modality branch. Our extensive experiments validate the efficacy of the proposed method, and our method achieves state-of-the-art performance on two public datasets. Code is available at https://github.com/qinghuannn/PAMFN.

Phosphorylation of human glioma-associated oncogene 1 on Ser937 regulates Sonic Hedgehog signaling in medulloblastoma.

Aberrant activation of sonic hedgehog (SHH) signaling and its effector transcriptional factor GLI1 are essential for oncogenesis of SHH-dependent medulloblastoma (MBSHH) and basal cell carcinoma (BCC). Here, we show that SHH inactivates p38α (MAPK14) in a smoothened-dependent manner, conversely, p38α directly phosphorylates GLI1 on Ser937/Ser941 (human/mouse) to induce GLI1's proteasomal degradation and negates the transcription of SHH signaling. As a result, Gli1S941E loss-of-function knock-in significantly reduces the incidence and severity of smoothened-M2 transgene-induced spontaneous MBSHH, whereas Gli1S941A gain-of-function knock-in phenocopies Gli1 transgene in causing BCC-like proliferation in skin. Correspondingly, phospho-Ser937-GLI1, a destabilized form of GLI1, positively correlates to the overall survival rate of children with MBSHH. Together, these findings indicate that SHH-induced p38α inactivation and subsequent GLI1 dephosphorylation and stabilization in controlling SHH signaling and may provide avenues for future interventions of MBSHH and BCC.

Transcriptomic analyses and machine-learning methods reveal dysregulated key genes and potential pathogenesis in human osteoarthritic cartilage.

Aims: This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Methods: Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization. Results: A total of 46 genes were obtained from the intersection of significantly upregulated genes in osteoarthritic cartilage and the key module genes screened by WGCNA. Functional annotation analysis revealed that these genes were closely related to pathological responses associated with OA, such as inflammation and immunity. Four key dysregulated genes (cartilage acidic protein 1 (CRTAC1), iodothyronine deiodinase 2 (DIO2), angiopoietin-related protein 2 (ANGPTL2), and MAGE family member D1 (MAGED1)) were identified after using machine-learning algorithms. These genes had high diagnostic value in both the training cohort and external validation cohort (receiver operating characteristic > 0.8). The upregulated expression of these hub genes in osteoarthritic cartilage signified higher levels of immune infiltration as well as the expression of metalloproteinases and mineralization markers, suggesting harmful biological alterations and indicating that these hub genes play an important role in the pathogenesis of OA. A competing endogenous RNA network was constructed to reveal the underlying post-transcriptional regulatory mechanisms. Conclusion: The current study explores and validates a dysregulated key gene set in osteoarthritic cartilage that is capable of accurately diagnosing OA and characterizing the biological alterations in osteoarthritic cartilage; this may become a promising indicator in clinical decision-making. This study indicates that dysregulated key genes play an important role in the development and progression of OA, and may be potential therapeutic targets.