Search Results (243)

Developmental dysplasia of the hip (DDH) is a congenital disorder influenced by genetic and epigenetic factors. This study aimed to elucidate the molecular pathogenesis of DDH through a comprehensive transcriptomic analysis, identifying differentially expressed genes (DEGs) and long non-coding RNAs (lncRNAs) in hip joint capsules from DDH patients and healthy controls. RNA sequencing data from 12 samples (6 DDH, 6 controls) were retrieved from the NCBI database. Functional annotation was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses via the DAVID tool. A protein–protein interaction (PPI) network of DEGs was constructed using STRING with medium confidence settings. Among 78,930 transcripts, 4.3% were significantly differentially expressed, according to DESeq2 analysis. A total of 3425 DEGs were identified (FDR < 0.05, |log2 FC| > 2), including 1008 upregulated and 2417 downregulated transcripts in DDH samples. Additionally, 1656 lncRNAs were detected among the DEGs. These findings enhance our understanding of the genetic and epigenetic landscape of DDH and highlight the involvement of key biological pathways such as cell cycle regulation and Wnt signaling. This study provides a foundation for future molecular research into the pathogenesis of DDH. Full article

The peach landrace ‘Liuyefeitao’ exhibits the unique reproductive trait of self-compatibility combined with cross-incompatibility, contrasting with typical Prunus species in this way. In preliminary studies involving controlled pollination assays, we showed complete pollen tube arrest in cross-pollinated styles, whereas self-pollination enabled full tube elongation. S-genotyping identified a homozygous S₂S₂ genotype with intact S₂-RNase but a truncated PpSFB2 due to a frameshift mutation. Transcriptome profiling of the styles revealed 7937 differentially expressed genes (DEGs) between self- and cross-pollination treatments, with significant enrichment in plant MAPK signaling, plant–pathogen interactions, and plant hormone signaling transduction pathways (|Fold Change| ≥ 2, FDR < 0.01). Notably, PpSLFL3 (a pollen F-box gene) showed down-regulation in cross-pollinated styles, as validated by means of qRT-PCR. Protein interaction assays revealed direct binding between PpSLFL3 and S₂-RNase via Y2H and BiFC analysis, suggesting its role in mediating SCF complex-dependent degradation. We propose that insufficient PpSLFL3 expression during cross-pollination disrupts SCF ubiquitin ligase complex-mediated degradation of non-self S₂-RNase, leading to the toxic degradation of RNA in pollen tubes by S₂-RNase. This mechanism is mechanistically similar to unilateral reproductive barriers in Solanaceae but represents a novel regulatory module in Rosaceae. Our findings provide critical insights into the evolution of cross-incompatibility systems and molecular breeding strategies for Prunus species. Full article

Real-time statistical inference plays a pivotal role in maritime Command and Control (C2) environments, particularly for applications such as satellite-based object detection and underwater signal interpretation. These contexts often require online multiple hypothesis testing mechanisms capable of sequential decision-making while preserving statistical rigor. A primary concern is the control of the False Discovery Rate (FDR), as erroneous detections can impair operational effectiveness. In this study, we investigate the robustness of the Levels based On Recent Discovery (LORD) algorithm under adversarial conditions by introducing controlled perturbations to the data stream—specifically, missing or corrupted p-values derived from simulated Gaussian distributions. Inspired by developments in corruption-aware multi-armed bandit models, we formulate adversarial scenarios and propose defense strategies that modify the LORD algorithm’s threshold sequence and integrate an online Benjamini–Hochberg procedure. The results, based on extensive Monte Carlo simulations, demonstrate that even a single missing p-value can trigger a cascading effect that reduces statistical power, and that our proposed mitigation strategies significantly improve algorithmic resilience while maintaining FDR control. These contributions advance the development of robust online statistical decision-making tools for real-time maritime surveillance systems operating under uncertain and error-prone conditions. Full article

Xerostomia, the subjective complaint of a dry mouth, is frequently associated with salivary flow reduction and/or salivary gland hypofunction. This condition significantly impacts an individual’s quality of life and oral health, including difficulties in speaking, chewing, and swallowing. Xerostomia may be caused by autoimmune diseases, xerogenic medications, and radiation therapy. Our objective was to identify differentially expressed proteins in the saliva of patients with medication and autoimmune disease-associated xerostomia compared to non-xerostomic control subjects. Two groups of individuals (N = 45 total) were recruited: non-xerostomic subjects (NX-group; n = 18) and xerostomic patients (XP-group; n = 27). Dried saliva spot samples were collected from major salivary glands, i.e., parotid (left and right) and submandibular glands. Proteomic analysis was performed by deep nanoLC-MS/MS. Differential protein expression in the XP-group relative to the NX-group was determined by the Mann–Whitney U-test with FDR Benjamini–Hochberg correction (p_adj < 0.05). The Search Tool for Recurring Instances of Neighboring Genes (STRING_v12.0) was used to generate interaction networks and perform pathway analysis. A total of 1407 proteins were detected. Of these, 86 from the left parotid gland, 112 from the right parotid gland, and 73 from the submandibular gland were differentially expressed proteins (DEPs). Using STRING analysis, we identified, for the first time, several neurodegenerative disease-associated networks, primarily involving the downregulation of the 20S proteasome core complex and glyoxalase proteins across salivary glands. In this study, we determined neuronal dysregulation and impaired methylglyoxal (MGO) detoxification, possibly through reduced protein expression of glyoxalase Parkinson’s Disease (PD) Protein 7 (encoded by the PARK7 gene) in major salivary glands of xerostomic patients. Indeed, impaired MGO detoxification has been previously shown to cause salivary gland dysfunction in a mouse model of type 2 diabetes. Based on other DEPs associated with neurodegenerative disorders, our results also suggest a possible deficiency in the parasympathetic nervous system innervation of salivary glands, warranting further investigation. Full article

Background/Objectives: Chronic manganese (Mn) exposure is a recognized environmental contributor to Parkinsonian syndromes, including Mn-induced Parkinsonism (MnIP). This study aimed to evaluate whole-blood Mn levels and investigate disease/exposure-status-related alterations in metabolomic and lipidomic profiles. Methods: A case–control study (N = 97) was conducted in Brescia, Italy, stratifying participants by Parkinsonism diagnosis and residential Mn exposure. Whole-blood Mn was quantified using ICP-MS. Untargeted metabolomic and lipidomic profiling was conducted using LC-MS. Statistical analyses included Mann–Whitney U tests, conditional logistic regression, ANCOVA, and pathway analysis. Results: Whole-blood Mn levels were significantly elevated in Parkinsonism cases vs. controls (median: 1.55 µg/dL [IQR: 0.75] vs. 1.02 µg/dL [IQR: 0.37]; p = 0.001), with Mn associated with increased odds of Parkinsonism (OR = 2.42, 95% CI: 1.13–5.17; p = 0.022). The disease effect metabolites included 3-sulfoxy-L-tyrosine (β = 1.12), formiminoglutamic acid (β = 0.99), and glyoxylic acid (β = 0.83); all FDR p < 0.001. The exposure effect was associated with elevated glycocholic acid (β = 0.51; FDR p = 0.006) and disrupted butanoate (Impact = 0.03; p = 0.004) and glutamate metabolism (p = 0.03). Additionally, SLC-mediated transmembrane transport was enriched (p = 0.003). The interaction effect identified palmitelaidic acid (β = 0.30; FDR p < 0.001), vitamin B6 metabolism (Impact = 0.08; p = 0.03), and glucose homeostasis pathways. In lipidomics, triacylglycerols and phosphatidylethanolamines were associated with the disease effect (e.g., TG(16:0_10:0_18:1), β = 0.79; FDR p < 0.01). Ferroptosis and endocannabinoid signaling were enriched in both disease and interaction effects, while sphingolipid metabolism was specific to the interaction effect. Conclusions: Mn exposure and Parkinsonism are associated with distinct metabolic and lipidomic perturbations. These findings support the utility of omics in identifying environmentally linked Parkinsonism biomarkers and mechanisms. Full article

Dietary bitter compounds such as caffeine have the potential to reduce backfat in pigs. However, the use of caffeine as a feed additive has restrictions in many countries. It was hypothesised that grape seed and gentian plant extracts (GG) could replace caffeine in feed due to their bitterness and antiadipogenic effects. The effect of caffeine (0.5 g/kg), GG (2 g/kg) alone or in combination with caffeine (BM) at increasing concentrations (0.5, 1, 1.5, or 2 g/kg) on feed efficiency, carcass, and meat quality was assessed in finishing pigs (Large White × Landrace). Growth performance and carcass traits were evaluated at a pen level (n = 14). Loins (longissimus thoracis) were removed from eight pig/treatment at the abattoir to assess drip loss, lightness (L*), redness (a*), yellowness (b*), chroma (C*), hue angle (h°), pH, cook loss, and shear force. A linear increase (p < 0.05) in loin a*, b*, and C* values and a linear decrease (p < 0.05) in ADFI, ADG, backfat, dressing percentage, and HSCW were observed with increasing BM levels. At 1.5 g/kg, BM increased the loins a* (p < 0.05), b* (p < 0.05) and C* values (p < 0.05) compared to the control. Twenty-two proteins related to energy metabolism and myofibril assembly were identified to be upregulated (FDR < 0.05) in BM vs. control loins. In conclusion, GG could be used in combination with low doses of caffeine to modulate appetite and carcass leanness and improve pork colour. Full article

Background/Objectives: Obesity is associated with cardiovascular disease worldwide. An increased lipoprotein A (LpA) level is an independent risk factor for cardiovascular disease in children. Genetic polymorphisms of the LPA gene may play an important role in susceptibility to obesity. The aim of this study was to investigate the association of LPA rs10455872 polymorphism with the risk and clinical phenotypes of childhood obesity. Methods: This study included 103 children with obesity and 77 healthy controls. Genotyping of the LPA rs10455872 polymorphism was performed using real-time PCR. Results: The genotype distributions of the LPA rs10455872 polymorphism did not differ significantly between children with obesity and healthy children (p = 0.563). A marked difference in insulin levels was observed between children with obesity carrying the AG (16.90 IU/mL) and AA (25.57 IU/mL) genotypes. A marked difference was also observed in CRP levels between children with obesity with the AG (2.31 mg/L) and AA (4.25 mg/L) genotypes. After correcting for multiple comparisons using the false discovery rate (FDR), significant differences were found between AG and AA genotypes in vitamin B12 (adjusted p = 0.024). Serum iron showed a borderline association (adjusted p = 0.072). A statistically significant correlation was found between the metabolic syndrome index and body fat ratio among children with obesity with the AA genotype (p = 0.028). Conclusions: Although limited by the small number of children with obesity with the AG genotype, some differences were noted between the AG and AA genotypes. These exploratory findings require further investigation in adequately powered studies. In children with obesity with the AA genotype, the metabolic syndrome index increases as the body fat ratio increases. Full article

Background: Alcohol withdrawal syndrome is a common clinical challenge that may lead to significant complications if not properly managed. Symptom-triggered therapy (STT) represents a promising alternative to fixed-dose regimens (FDRs) providing benzodiazepine prescriptions based on objectively quantified withdrawal symptoms. This study aimed to evaluate the effectiveness and safety of STT using the Hamburg Alcohol Withdrawal Scale (HAES) compared to FDRs in the management of inpatient alcohol detoxification. Methods: In a retrospective case–control study, alcohol detoxification treatment in STT was compared with FDRs. During a twelve-month observation period, a total of 123 patients in the STT group were recruited and compared with 123 controls in the FDR group (matched according to sex, age, and current amount of alcohol consumption) treated in the same hospital before the implementation of STT. The study outcomes included the total benzodiazepine dosage, duration of acute detoxification phase, length of inpatient stay, and occurrence of complications such as epileptic seizures and delirium tremens. Results: STT showed a significantly lower total benzodiazepine dosage (22.50 mg vs. 115.00 mg, p < 0.001), a shorter duration of the detoxification phase (48.00 h vs. 201.75 h, p < 0.001), and a reduced length of inpatient stay (23.00 days vs. 28.00 days, p = 0.003) compared to FDRs. There were no significant differences in the rates of complications between the two settings. Linear mixed model analysis revealed that the differences remained highly significant even after adjusting for various explanatory variables (i.e., age, sex, standard units of alcohol, psychiatric comorbidities, treatment discontinuation, and occurrence of any complication). Conclusions: STT appears to be as effective and safe as traditional fixed-dose regimens of benzodiazepines for the management of inpatient alcohol detoxification. This approach may thereby minimize unnecessary pharmacological exposure, facilitate the earlier integration of patients into psychoeducational and psychosocial interventions, and reduce healthcare costs. Full article

Background: Bambusaoldhamii is an important economic bamboo species. However, flowering occurred after its introduction and cultivation, resulting in damage to the economy of bamboo forests. Currently, the molecular mechanism of flowering induced by introduction stress is still unclear. This study systematically explored the key genes and regulatory pathways of flowering in Bambusaoldhamii under introduction stress through field experiments combined with transcriptome sequencing and weighted gene co-expression network analysis (WGCNA), with the aim of providing a basis for flower-resistant cultivation and molecular breeding of bamboo. Results: The study conducted transcriptome sequencing on flowering and non-flowering Bambusaoldhamii bamboo introduced from Youxi, Fujian Province for 2 years, constructed a reference transcriptome containing 213,747 Unigenes, and screened out 36,800–42,980 significantly differentially expressed genes (FDR < 0.05). The results indicated that the photosensitive gene CRY and the temperature response gene COR413-PM were significantly upregulated in the flowering group; the expression level of the heavy metal detoxification gene MT3 increased by 27.77 times, combined with the upregulation of the symbiotic signaling gene NIN. WGCNA analysis showed that the expression level of the flower meristem determination gene AP1/CAL/FUL in the flowering group was 90.38 times that of the control group. Moreover, its expression is regulated by the cascade synergy of CRY-HRE/RAP2-12-COR413-PM signals. Conclusions: This study clarifies for the first time that the stress of introducing Bambusaoldhamii species activates the triad pathways of photo-temperature signal perception (CRY/COR413-PM), heavy metal detoxification (MT3), and symbiotic regulation (NIN), collaboratively driving the AP1/CAL/FUL gene expression network and ultimately triggering the flowering process. Full article

Noise-induced hearing loss (NIHL) is a significant occupational health issue, characterized by permanent damage to the cochlea due to prolonged exposure to high-intensity noise. Circulating microRNAs (c-miRNAs) have emerged as promising non-invasive indicators of inner ear pathology and potential modulators of cellular stress responses. Nevertheless, their specific roles in NIHL remain inadequately characterized. This study evaluated miRNA expression in the peripheral blood of individuals with bilateral NIHL (n = 12) and matched healthy controls (n = 6) using GeneChip^® miRNA 4.0 arrays. The Transcriptome Analysis Console software was used for differential expression analysis, and bioinformatic predictions of gene targets and pathway enrichment were performed using TargetScan (version 8.0) and the Enrichr tool. Among the 72 differentially expressed miRNAs (FDR < 0.05), hsa-miR-486-2, hsa-miR-664b-3p, hsa-miR-4485, hsa-miR-501, and hsa-miR-663b were notably upregulated, while hsa-miR-6723, hsa-miR-194-2, hsa-miR-668-5p, hsa-miR-4722-3p, and hsa-miR-4716 showed significant downregulation. Enrichment analyses indicated involvement in apoptosis regulation, mitochondrial stability, and cell cycle control. Principal component analysis (PCA) and clustering methods revealed clear molecular distinctions between the patient and control groups. The observed alterations in c-miRNA profiles highlight their relevance to NIHL-related cellular stress and degeneration. These findings support their utility as candidate biomarkers for diagnosis and prognosis, warranting further validation in functional and longitudinal studies. Full article

Background: Exfoliation glaucoma (XFG) represents a form of deleterious ocular aging of unclear etiology. We evaluated prediagnostic nuclear magnetic resonance (NMR)-based metabolites in relation to XFG risk, expanding on our prior findings of XFG-related metabotypes using liquid chromatography-mass spectrometry (LC-MS). Methods: We identified 217 XFG cases and 217 matched controls nested within three prospective health professional cohorts with plasma collected a mean 11.8 years before case identification. Plasma metabolites were analyzed using the targeted NMR Nightingale platform. Conditional logistic models and Metabolite Set Enrichment Analysis were performed. Multiple comparison issues were addressed using the number of effective tests (NEF) and false discovery rate (FDR). Results: Among 235 profiled metabolites, higher glucose was significantly associated with a lower risk of XFG (odds ratio (95%CI) = 0.42 (0.26, 0.7); NEF = 0.03). Among metabolite classes, lipoprotein subclasses and branched-chain amino acids were inversely associated, while relative lipoprotein lipid concentrations were adversely associated (FDR < 0.05). Conclusion: NMR profiling revealed that glucose, branched-chain amino acids, lipoprotein subclasses, and relative lipoprotein lipid concentrations may play important roles in XFG etiology. Full article

Following the emergence of COVID-19, breakthrough SARS-CoV-2 infections have demonstrated substantial heterogeneity in both occurrence and clinical severity. This case–control study aimed to elucidate the factors associated with the incidence, duration, and severity of SARS-CoV-2 symptoms among Chinese adults during the Omicron wave. The analysis was based on data from a national COVID-19 surveillance program encompassing six provinces—Jiangsu, Chongqing, Shandong, Hunan, Anhui, and Yunnan—and included both laboratory-confirmed and clinically diagnosed cases. Data were systematically collected between February and April 2023. For each confirmed case, a matched control was selected through simple random sampling, matched on sex, age (±5 years), and province of residence. Multivariate logistic regression analyses were employed to assess a range of potential determinants, including demographic characteristics, lifestyle behaviors, and pre-existing medical conditions, in relation to the risk of infection, as well as the persistence and severity of symptoms following SARS-CoV-2 breakthrough infection. A total of 10,426 cases and 10,426 matched controls were included in the final analysis. Among the infected individuals, 963 (9.24%) reported persistent symptoms, while 773 (7.41%) experienced moderate-to-severe clinical manifestations. Occasional alcohol consumption, presence of comorbidities, tea and coffee intake, overweight status, and a longer interval since the last vaccination dose were all significantly associated with increased odds of infection (OR > 1, FDR < 0.05). Conversely, weekly alcohol consumption and smoking were associated with a decreased risk (OR < 1, FDR < 0.05). Female sex was significantly associated with both persistent and moderate-to-severe symptoms. Additional risk factors for prolonged or severe symptoms included older age, being underweight or overweight, a history of immunotherapy, coffee consumption, and the presence of comorbidities. These findings underscore the multifactorial nature of SARS-CoV-2 infection outcomes and highlight the interplay between host characteristics and behavioral factors. The results support the development of personalized prevention strategies aimed at reducing the clinical burden and long-term impact of COVID-19. Full article

The signals of high-speed train traction motor bearings contain strong noise and exhibit non-linear and non-Gaussian characteristics. To address the aforementioned issues, this paper proposes a method that combines Kernel Independent Component Analysis and Deep Principal Component Analysis (KICA-DPCA) to improve the accuracy of bearing fault detection. Firstly, DPCA is utilized to thoroughly extract fault information from the dataset while simultaneously achieving the purpose of noise reduction. Secondly, KICA is combined to project the data into a high-dimensional feature space and extract independent components, thereby separating the data into two groups following Gaussian and non-Gaussian distributions. Furthermore, the occurrence of bearing faults is determined by evaluating the statistical residuals against the predefined threshold. Finally, the proposed algorithm is validated on both simulation data from the Traction Drive Control System-Fault Injection Benchmark (TDCS-FIB) platform and experimental data from the Case Western Reserve University bearing fault dataset. Comparative tests are conducted using the false alarm rate (FAR) and fault detection rate (FDR) as evaluation metrics, which fully demonstrate the effectiveness and superiority of the proposed method. Full article

Transcranial direct current stimulation (tDCS) is a safe, well-tolerated method of non-invasively eliciting cortical neuromodulation. It has gained recent interest, especially for its positive clinical outcomes in neurodegenerative diseases such as multiple sclerosis (MS). However, its simultaneous (during tDCS) and cumulative effects (following repeated tDCS sessions) on the regional brain activity during rest need further investigation, especially in MS. This study aims to elucidate tDCS’ underpinnings, alongside its therapeutic impact in MS patients, using concurrent tDCS-MRI methods. In total, 20 MS patients (age = 48 ± 12 years; 8 males) and 28 healthy controls (HCs; age = 36 ± 15 years; 12 males) were recruited. They participated in a tDCS-MRI session, during which resting-state functional MRI (rs-fMRI) was used to measure the levels of the fractional amplitude of low-frequency fluctuations (fALFFs), which is an index of regional neuronal activity, before and during left anodal dorsolateral prefrontal cortex (DLPFC) tDCS (2.0 mA for 15 min). MS patients were then asked to return for an identical tDCS-MRI visit (follow-up) after 20 identical at-home tDCS sessions. Simultaneous tDCS-induced changes in fALFF are seen across cortical and subcortical areas in both HC and MS patients, with some regions showing increased and others decreased brain activity. In HCs, fALFF increased in the right pre- and post-central gyrus whilst it decreased in subcortical regions. Conversely, MS patients initially displayed increases in more posterior cortical regions but decreases in the superior and temporal cortical regions. At follow-up, MS patients showed reversed patterns, emphasizing significant cumulative effects of tDCS treatment upon brain excitation. Such long-lasting changes are further supported by greater pre-tDCS fALFFs measured at follow-up compared to baseline, especially around the cuneus. The results were significant after correcting for multiple comparisons (p-FDR < 0.05). Our study shows that tDCS has both simultaneous and cumulative effects on neuronal activity measured with rs-fMRI, especially involving major brain areas distant from the site of stimulation, and it is responsible for fatigue and cognitive and motor skills. Full article

Introduction: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS) that leads to inflammation and demyelination, manifesting in either a relapsing–remitting or progressive form. As a multifactorial disease, MS involves both genetic and environmental factors, with a known significant contribution from human leukocyte antigen (HLA) genes, mainly represented by the HLA-DRB1 and HLA-DQB1 loci, which have been linked to either susceptibility or protection, but variably across populations and ethnic groups. We aimed to study the distribution and polymorphism of HLA-DRB1 and HLA-DQB1 alleles in a population with MS from the southern Moroccan region, in comparison with healthy controls. Materials and Methods: A cross-sectional study was conducted over a period of 2 years (2022–2024) in a MS cohort including 40 patients and 100 healthy controls. DRB1 and DQB1 HLA genotyping was performed using a high-resolution reverse sequence-specific oligonucleotide (SSO) method, based on the Luminex system (xMAP technology, One lambda^®). Data were analyzed using SPSS 26; differences in allele frequencies were evaluated by the Chi-square test and Fisher’s exact test. OR (95% CI) was calculated, and FDR corrections were applied for multiple testing. Results: Among the various HLA-DRB1 and DQB1 alleles studied, including those considered as predisposing to MS, the DQB1*02:01 and DRB1*15:01 alleles were more prevalent in MS patients, with 40% and 8.8% vs. 16% and 4.08% in controls respectively, although these differences were not statistically significant (p = 0.06 and p = 0.12). Likewise, the DRB1*15:01-DQB1*06:02 association was significantly more prevalent in the MS group (9%, p = 0.004). In contrast, the DRB1*07:01 allele, linked to protection against MS in many populations, was significantly predominant in controls (17%, p = 0.004). Similarly, the DRB1*07:01–DQB*02:01 combination was rather more frequent in controls (12%, p = 0.01). Confronted to MS clinical forms, we remarkably noted that the DRB1*13:03 allele was found only among relapsing–remitting MS (RRMS) patients (6%, p = 0.003), while DQB1*02:01 was significantly associated with RRMS (42.1%) and primary progressive MS (41%, p = 0.001), with an intermediate Expanded Disability Status Scale (EDSS) score, which may indicate a possible link with disease progression and severity. Conclusions: The results of our study highlighted particular HLA alleles, DRB1 and DQB1, alone or in combination, as potential immunogenic factors of susceptibility to MS in a population from southern Morocco, while other alleles seem rather to protect against the disease. This HLA polymorphism is also reflected in the clinical forms of the disease, showing a tendency toward severity for certain alleles. However, such preliminary results need to be consolidated and confirmed by studies carried out on a larger population sample, and compared with others on a national scale. Full article