Search Results (73)

The lactoperoxidase system (LpoS) is an enzymatic antimicrobial mechanism of saliva that oxidizes (pseudo)halide substrates to reactive compounds capable of limiting microbial growth. This study evaluated how different LpoS variants—utilizing iodide (LpoS-I⁻), thiocyanate (LpoS-SCN⁻), selenocyanate (LpoS-SeCN⁻), and a thiocyanate–iodide mixture (LpoS-SCN⁻ + I⁻)—affect virulence, metabolism, and biofilm structure in Streptococcus mutans. Using qRT-PCR, pyruvate assays, MTT reduction, and confocal microscopy, we found that LpoS-I⁻ most effectively reduced atpD and ldh expression, impaired acid tolerance, and decreased lactate and pyruvate production. LpoS-SCN⁻ and LpoS-SeCN⁻ also downregulated atpD and gtfB, although LpoS-SeCN⁻ upregulated ldh. Despite minimal structural biofilm disruption, LpoS-I⁻ markedly inhibited intracellular and extracellular pyruvate accumulation, suggesting altered glycolytic flux. These findings indicate that iodide-based LPO systems modulate key metabolic and regulatory pathways in S. mutans and may hold potential for inclusion in anticaries oral formulations. Full article

Background: Previous attempts to classify lymphoma subtypes based on metabolic features extracted from ¹⁸F-FDG PET imaging have been hindered by inconsistencies in imaging protocols, scanner types, and inter-institutional variability. To overcome these limitations, we propose a multimodal deep learning framework that integrates harmonized PET imaging features with structured clinical information. The proposed framework is designed to perform hierarchical classification of clinically meaningful lymphoma subtypes through two sequential binary classification tasks. Methods: We collected multi-center data comprising ¹⁸F-FDG PET images and structured clinical variables of patients with lymphoma. To mitigate domain shifts caused by different scanner manufacturers, we integrated a Scanner-Conditioned Normalization (SCN) module, which adaptively harmonizes feature distributions using manufacturer-specific parameters. Performance was validated using internal and external cohorts, with the statistical significance of performance gains assessed via DeLong’s test and bootstrap-based CI analysis. Results: The proposed model achieved an area under the curve (AUC) of 0.89 (internal) and 0.84 (external) for Hodgkin lymphoma versus non-Hodgkin lymphoma classification and 0.84 (internal) and 0.76 (external) for diffuse large B-cell lymphoma versus follicular lymphoma classification (p > 0.05). These results were obtained using a multimodal model that integrated anterior and lateral maximum intensity projection (MIP) images with clinical data. Conclusions: This study demonstrates the potential of a deep learning-based approach for lymphoma subtype classification using non-invasive ¹⁸F-FDG PET imaging combined with clinical data. While further validation in larger, more diverse cohorts is necessary to address the challenges of rare subtypes and biological heterogeneity, LymphoMAP serves as a meaningful step toward developing assistive tools for early clinical decision-making. These findings underscore the feasibility of using automated pipelines to support, rather than replace, conventional diagnostic workflows in personalized lymphoma management. Full article

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a congenital cardiac disorder, but its severity has been increasingly linked to inflammatory processes. This study aimed to investigate gene expression profiles in ARVC to identify genes potentially driving inflammation in affected individuals. Methods: Publicly available gene expression datasets comprising 12 ventricular tissue samples from six clinically confirmed ARVC patients (paired left and right ventricular biopsies) and 12 ventricular samples from six non-failing donor hearts were analyzed to identify differentially expressed genes. Immune infiltration was assessed to determine the proportions of immune cells in the ARVC condition. Correlation analysis between immune cell proportions and gene expression profiles was further performed to identify genes linked with inflammation-specific immune cells. Functional enrichment analysis of associated genes was performed to pinpoint the key involvement of genes in different inflammatory-specific pathways. Finally, the key gene associated with inflammation-specific immune cells and its active involvement in inflammatory pathways was further subjected to molecular docking against a curated library of marine-derived phytochemicals, followed by 100 ns molecular dynamics simulations to evaluate ligand stability. Results: A total of 141 significantly upregulated genes were identified in ARVC. Immune infiltration analysis revealed elevated proportions of regulatory T cells, CD8⁺ T cells, plasma cells, M2 macrophages, resting mast cells, and activated NK cells in the ARVC phenotype, indicating an immunologically active microenvironment. Correlation analysis identified four genes—LIFR, SCN2B, RGCC, and PIK3R1—showing significant positive associations with these immune cells. Functional enrichment analysis highlighted PIK3R1 (LogFC > 2.00) as a central regulator in the PI3K/AKT and mTOR pathways, which govern immune activation, cell survival, and fibrosis. Molecular docking identified two marine compounds, CMNPD18967 and CMNPD756, with strong binding affinities (−5.9 and −5.7 kcal/mol, respectively). Molecular dynamics simulations confirmed stable ligand binding within the PIK3R1 active site. Conclusions: PIK3R1 emerges as a key inflammation-associated gene in ARVC, with strong involvement in immune-regulatory pathways. Marine-derived phytochemicals CMNPD18967 and CMNPD756 demonstrate promising inhibitory potential through stable interaction with PIK3R1. While these findings present potential anti-inflammatory leads, validation in larger clinical cohorts and experimental models is essential to confirm translational applicability. Full article

Lanthanide-based single-molecule magnets (Ln-SMMs) showing stimuli-responsive changes in photoluminescence (PL) and magnetic properties are attractive for their potential applications in information storage and molecular devices. In this work, we report two mononuclear complexes, namely, Dy(SCN)₂(NO₃)(Cl-depma)₂(4-hpy)₂ (Dy-Cl) and Dy(SCN)₂(NO₃)(Br-depma)₂(4-hpy)₂ (Dy-Br), where X-depma represents 10-X-9-diethylphosphinomethylanthracene (X = Cl, Br) and 4-hpy is 4-hydroxypyridine. Both contain face-to-face π-π-interacted anthracene rings and exhibit yellow-green excimer emission. Unlike the other related Dy–anthracene complexes without a halogen substituent, Dy-Cl and Dy-Br cannot undergo photocycloaddition reaction under UV-light irradiation. However, they exhibited remarkable grinding-induced changes in luminescence. Magnetic studies revealed that Dy-Cl and Dy-Br show SMM behavior under zero dc field with the effective energy barriers (U_eff/k_B) of 259 K and 264 K, respectively. We also investigated the effect of pressure on the magnetic properties of Dy-Br and observed a reduction in the magnetization value, narrowing of the butterfly-shaped hysteresis loop, and acceleration of the magnetic relaxation under 1.09 GPa. The results demonstrate that introducing a halogen substituent into an anthracene group may pose significant influences on the photophysical and photochemical properties of the complexes. In addition, pressure may be a promising external stimulus to modulate the PL and SMM behaviors of Dy–anthracene complexes. Full article

Reproductive and growth traits are key economic traits in sheep. This study aims to identify key single nucleotide polymorphisms (SNPs) and candidate genes associated with reproductive and growth traits in Tianmu polytocous sheep through a genome-wide association study (GWAS). The findings are expected to provide both a theoretical foundation for molecular breeding in this breed and novel insights into the genetic basis of ovine reproductive and growth performance. This study took 483 adult Tianmu polytocous ewes as the research subjects, collected their lambing records, measured their phenotypic values of growth traits (3 weight and 11 body size traits), and collected their blood samples for whole-genome resequencing to identify SNPs in the Tianmu polytocous sheep genome. The results identified a total of 9,499,019 (3× coverage) and 27,413,216 (30× coverage) high-quality SNPs in the Tianmu polytocous sheep genome. Subsequently, the association analysis between SNPs and reproductive and growth traits was conducted using a mixed linear model. A total of 92, 66, 18, 28, 6, 42, 3, 3, 6, 1, 12, 3, 22, 8, 6, and 3 SNPs were found associated with litter size at first parity, litter size at second parity, litter size at third parity, litter size at fourth parity, birth weight, weaning weight, body height, withers height, body length, head length, head width, cannon bone circumference, forelimb height, chest girth, chest depth, and withers width, respectively. Further, based on SNP annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, candidate genes associated with the reproductive and growth traits were identified. Among these genes, 11 LOC, DEPTOR, GNG12, GRM7, PTH, PTH2R, WWOX, INHA, and NRG3 are candidate genes associated with litter size at first parity or litter size at third parity. These genes are involved in the G protein-coupled receptor signaling pathway, G protein-coupled receptor activity, ovarian tissue development, and hormone secretion. Additionally, TFRC and NTN1 are candidate genes associated with birth weight, while five UGT1A and CASR are candidate genes associated with weaning weight. These candidate genes are primarily involved in lipid metabolism. Finally, the following genes were identified as candidates associated with specific traits: DLG2, TMEM126A, and TMEM126B with body height; DSCAM and SCN8A with body length; BARX1 with cannon bone circumference; four LOC genes with forelimb height; EPHA4 with chest depth; and MRS2 with withers width. Full article

Background: Staphylococcus aureus is a major zoonotic and foodborne pathogen with substantial One Health implications, yet its prevalence, resistance, and virulence potential within the aquaculture sector in Nigeria remains poorly characterized. Objectives: To supplement existing information, this current study investigated the prevalence, clonal distribution, antimicrobial resistance, and virulence gene profiles of S. aureus isolates from fish, fish water, and occupationally exposed fish handlers in Anambra State, Southeast Nigeria. Methods: A total of 607 samples—comprising 465 surface swabs from raw and processed fish, 36 fish water samples, and 106 nasal swabs from fish handlers—were processed using selective culture, biochemical tests, antimicrobial susceptibility testing, DNA microarray analysis, spa typing, and SCCmec typing. Results: S. aureus was recovered from 16.5% (100/607) of the samples. Fourteen (14%) isolates were methicillin-resistant (MRSA), harboring mecA and SCCmec types IV and V, with a combined MRSA prevalence of 2.3%. Multidrug resistance was observed in 52.2% of isolates (mean Multiple Antimicrobial Resistance index: 0.23), with 19 resistance genes spanning nine antimicrobial classes—including heavy metal and biocide resistance. Twenty-eight spa types across 13 clonal complexes (CCs) were identified, with CC1, CC5, and CC8 predominating. The detection of shared spa types between fish and handlers indicates potential cross-contamination. Detected virulence genes included those for accessory gene regulators (agrI-IV), Pantone–Valentine leucocidin (lukFS-PV), toxic shock syndrome (tsst-1), hemolysins (hla, hlb, hld/hlIII, hlgA), biofilm formation (icaA, icaD), immune evasion (chp, scn, sak), enterotoxins (sea, seb, sec, sed, egc, and others), exfoliative toxins (etA, etB), epidermal cells differentiation (edinA, edinB), and capsular types (cap5, cap8). Conclusions: This study reveals that the aquaculture sector in Southeast Nigeria serves as a significant reservoir of genetically diverse, multidrug-resistant S. aureus strains with robust virulence profiles. These findings highlight the necessity of integrated One Health surveillance and targeted interventions addressing antimicrobial use and hygiene practices within aquatic food systems. Full article

Background/Objective: Noninvasive PET imaging-based assessment of PD-L1 expression is of high clinical value for better patient selection and treatment response rates to PD-L1 immunotherapies. Due to their shorter biological half-life and faster clearance from the blood pool, radiolabeled antibody fragments are an attractive alternative for imaging than their full-length IgG counterpart. This work investigated the radiosynthesis and in vitro cell uptake of anti-PD-L1-B11-nanobody radiolabeled with ⁴⁴Sc (t_1/2 = 4.04 h) as an alternative to anti-PD-L1-B11-IgG, better suited for longer half-life radioisotopes such as ⁸⁹Zr (t_1/2 = 78.41 h). Methods: The proteins were conjugated with p-SCN-Bn-DTPA and radiolabeled at room temperature with ⁴⁴Sc, achieving a radiochemical yield of a RCY of 94.8 ± 3.1% (n = 3) for [⁴⁴Sc]Sc-B11-IgG and 73.6 ± 12.1% (n = 3) for [⁴⁴Sc]Sc-B11-nanobody, before purification. Results: Significantly higher uptake in the PD-L1₊ cells than PD-L1_KO cells was observed for both probes. However, high non-specific uptake, particularly of the radiolabeled B11-nanobody, was also observed which may negatively impact its potential as a molecular imaging probe. Conclusions: Due to the high non-specific uptake in vitro, the ⁴⁴Sc radiolabeled nanobody was not progressed to further in vivo evaluation. These results should, however, not discourage future evaluations of other nanobody based probes radiolabeled with ⁴⁴Sc, due to their well-matched biological and physical half-life. Full article

Staphylococcus aureus (S. aureus) colonizes the nasal cavities of both healthy individuals and patients with chronic rhinosinusitis (CRS) with (CRSwNP) and without (CRSsNP) nasal polyps. Treatment-resistant S. aureus biofilms and intracellular persistence are common in CRS patients, requiring the expression of specific virulence factor genes to transition into these forms. We hypothesized that S. aureus isolates from non-diseased controls, CRSsNP patients, and CRSwNP patients would exhibit distinct virulence factor patterns contributing to persistence and intracellular survival in CRS patients. Nasal swabs from seventy-seven individuals yielded S. aureus cultures in eight non-diseased controls, eight CRSsNP patients, and five CRSwNP patients. Whole-genome sequencing analyzed stress, antimicrobial resistance, and virulence genes, including plasmids and prophages. Four virulence factor gene patterns emerged: a core set (hlgA, icaC, hlgB, hlgC, hld, and aur) present in all isolates, and accessory sets, including the enterotoxin gene cluster (seo, sem, seu, sei, and sen) and a partial/complete invasive virulence factor set (splE, splA, splB, lukE, and lukD) (p = 0.001). CRSwNP isolates exhibited incomplete carriage of the core set, with frequent loss of scn, icaC, and hlgA (p < 0.05). These findings suggest that S. aureus has clusters of virulence factors that may act in concert to support the survival and persistence of the bacteria, resulting in enhanced pathogenicity. This may manifest clinically with resistant disease and refractoriness to antibiotics. Full article

Myocardial Bridging (MB) is typically a benign congenital coronary anomaly. MB can infrequently result in complications such as myocardial ischemia, arrhythmias, and sudden cardiac death. Recent studies suggest an underlying genetic component for MB involving DES, FBN1, SCN2B, or NOTCH1. The role of percutaneous coronary intervention (PCI) in managing MB, compared to optimal medical therapy (OMT), remains uncertain. Our study used the National Inpatient Sample (NIS) Database to identify patients aged 18 or older with myocardial bridging who were managed with PCI versus medical therapy. We compared the outcomes between both groups including in-hospital mortality, the trend of management of MB and other in-hospital outcomes or complications. Our results showed no statistically significant difference between both subgroups when comparing in-hospital mortality and secondary outcomes of cardiac arrest and the development of an acute kidney injury (AKI). Patients with myocardial bridging treated with PCI had a higher risk of developing cardiogenic shock, requiring LVAD, and requiring the use of intra-aortic balloon pump (IABP) compared to the medical therapy subgroup. Our study suggests the decision to perform PCI in myocardial bridging patients should be individualized such as in patients with refractory symptoms despite medical therapy or those with known high-risk features. Full article

Photocatalytic degradation is a leading technology for complete mineralization of organic dyes in the ocean. In this work, a new viologen-bearing silver-thiocyanate-based photocatalyst, i.e., {(i-PrV)[Ag₂(SCN)₄]}_n (i-PrV²⁺ = isopropyl viologen) has been synthesized and structurally determined, with results showing that it can exhibit excellent degradation performance on rhodamine B (RhB) in artificial seawater. The planar i-PrV²⁺ dications are confined in the free voids of the [Ag₂(SCN)₄]_n²ⁿ⁻ layer with a two-dimensional (6,3) mesh, and strong C-H···S hydrogen bonds contribute to its structural stabilization. This photocatalyst was further characterized by powder X-ray diffraction (PXRD), UV-Vis, fluorescence, and photo/electrical responsive measurements, pointing to its application in visible-light-driven catalysis. Interestingly, using this photocatalyst, good photocatalytic degradation performance on rhodamine B in artificial seawater could be observed. The dye pollutant could be degraded with a high degradation ratio of 87.82% in 220 min. This work provides a promising catalyst for organic dye-type ocean pollutant treatments. Full article

The search for new heterometallic metal pseudohalides will be significant for the development of novel functional materials. In this work, a new silver/cadmium heterometallic thiocyanate templated by benzyl viologen has been synthesized and structurally determined, i.e., {(BV)[Ag₂Cd(SCN)₆]}_n (BV²⁺ = benzyl viologen). The interesting 1-D double chain [Ag₂Cd(SCN)₆]_n²ⁿ⁻ was constructed from the CdN₆ octahedron and Ag₂SCN₆ dimers via μ₂-SCN and μ₃-S,S N SCN bridge, in which the Ag···Ag interaction can be found. Inter-molecular C-H···S/N hydrogen bonds between BV²⁺ cations and [Ag₂Cd(SCN)₆]_n²ⁿ⁻ chains contribute to the formation of a stable 3-D network. The short S···N distance implies the strong charge transfer (CT) interactions between the electron-rich silver/cadmium thiocyanate donor and BV²⁺ acceptor. This hybrid can exhibit a photo-generated current performance with an intensity of 1.75 × 10⁻⁸ A. Interestingly, this hybrid can present good photocatalytic degradation performance on rhodamine B in artificial seawater with a degradation ratio of 86.5% in 240 min. This work provides a new catalyst way for the organic dye-type ocean pollutant treatments. Full article

Patulin, an emerging mycotoxin with high toxicity, poses great risks to public health. Considering the poor antibody production in patulin immunization, this study focuses on the four-dimensional data-independent acquisition (4D-DIA) quantitative proteomics to reveal the immune response of patulin in rabbits. The rabbit immunization was performed with the complete developed antigens of patulin, followed by the identification of the immune serum. A total of 554 differential proteins, including 292 up-regulated proteins and 262 down-regulated proteins, were screened; the differential proteins were annotated; and functional enrichment analysis was performed. The differential proteins were associated with the pathways of metabolism, gene information processing, environmental information processing, cellular processes, and organismal systems. The functional enrichment analysis indicated that the immunization procedures mostly resulted in the regulation of biochemical metabolic and signal transduction pathways, including the biosynthesis of amino acid (glycine, serine, and threonine), ascorbate, and aldarate metabolism; fatty acid degradation; and antigen processing and presentation. The 14 key proteins with high connectivity included G1U9T1, B6V9S9, G1SCN8, G1TMS5, G1U9U0, A0A0G2JH20, G1SR03, A0A5F9DAT4, G1SSA2, G1SZ14, G1T670, P30947, P29694, and A0A5F9C804, which were obtained by the analysis of protein–protein interaction networks. This study could provide potential directions for protein interaction and antibody production for food hazards in animal immunization. Full article

The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a (MIR-146A) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between these SNVs and susceptibility to drug-resistant and drug-responsive TLE in Brazil. Thus, deoxyribonucleic acid (DNA) samples from 120 patients with TLE (55 drug-responsive and 65 drug-resistant) were evaluated by real-time polymerase chain reaction (RT-PCR). A total of 1171 healthy blood donor individuals from the Online Archive of Brazilian Mutations (ABraOM, from Portuguese Arquivo Brasileiro On-line de Mutações), a repository containing genomic variants of the Brazilian population, were added as a control population for the studied SNVs. MIR-146A and SCN1A relative expression was performed by quantitative RT-PCR (qRT-PCR). The statistical analysis protocol was performed using an alpha error of 0.05. TLE patient samples and ABraOM control samples were in Hardy–Weinberg equilibrium for all studied SNVs. For rs2910164, the frequencies of the homozygous genotype (CC) (15.00% vs. 9.65%) and C allele (37.80% vs. 29.97%) were superior in patients with TLE compared to controls with a higher risk for TLE disease [odds ratio (OR) = 1.89 (95% confidence interval (95%CI) = 1.06–3.37); OR = 1.38 (95%CI = 1.04–1.82), respectively]. Drug-responsive patients also presented higher frequencies of the CC genotype [21.81% vs. 9.65%; OR = 2.58 (95%CI = 1.25–5.30)] and C allele [39.09% vs. 29.97%; OR = 1.50 (95%CI = 1.01–2.22)] compared to controls. For rs2298771, the frequency of the heterozygous genotype (AG) (51.67% vs. 40.40%) was superior in patients with TLE compared to controls with a higher risk for TLE disease [OR = 2.42 (95%CI = 1.08–5.41)]. Drug-resistant patients presented a higher AG frequency [56.92% vs. 40.40%; OR = 3.36 (95%CI = 1.04–17.30)] compared to the control group. For rs3812718, the prevalence of genotypes and alleles were similar in both studied groups. The MIR-146A relative expression level was lower in drug-resistant compared to drug-responsive patients for GC (1.6 vs. 0.1, p-value = 0.049) and CC (1.8 vs. 0.6, p-value = 0.039). Also, the SCN1A relative expression levels in samples from TLE patients were significantly higher in AG [2.09 vs. 1.10, p-value = 0.038] and GG (3.19 vs. 1.10, p-value < 0.001) compared to the AA genotype. In conclusion, the rs2910164-CC and rs2298771-AG genotypes are exerting significant risk influence, respectively, on responsive disease and resistant disease, probably due to an upregulated nuclear factor kappa B (NF-kB) and SCN1A loss of function. Full article

Sickle cell nephropathy (SCN) is a common complication of sickle cell disease (SCD) that significantly contributes to morbidity and mortality. In addition to clinical and life-style factors, genetic variants influence this risk. We performed a systematic review, searching five databases. Studies evaluating the effect of genetic modifiers on SCN were eligible. Twenty-eight studies (fair-to-good quality) were included: one genome-wide association study, twenty-six case-control studies, and one article combining both approaches. APOL1 was significantly associated with albuminuria and hyperfiltration in children and with worse glomerular filtration in adults. On the other hand, alpha-thalassemia protected patients against albuminuria and hyperfiltration, while BCL11A variants were protective against albuminuria alone. The HMOX1 long GT-tandem repeat polymorphism led to a lower glomerular filtration rate. No modifiers for the risk of hyposthenuria were identified. A genome-wide association approach identified three new loci for proteinuria (CRYL1, VWF, and ADAMTS7) and nine loci were linked with eGFR (PKD1L2, TOR2A, CUBN, AGGF1, CYP4B1, CD163, LRP1B, linc02288, and FPGT-TNNI3K/TNNI3K). In conclusion, this systematic review supports the role of genetic modifiers in influencing the risk and progression of SCN. Incorporating and expanding this knowledge is crucial to improving the management and clinical outcomes of patients at risk. Full article

Goats belong to a group of animals called small ruminants and are critical sources of livelihood for rural people. Genomic sequencing can provide information ranging from basic knowledge about goat diversity and evolutionary processes that shape genomes to functional information about genes/genomic regions. In this study, we exploited a whole-genome sequencing data set to analyze the genetic diversity, population structure and selection signatures of 44 individuals belonging to 5 Ethiopian goat populations: 12 Aberegalle (AB), 5 Afar (AF), 11 Begait (BG), 12 Central highlands (CH) and 5 Meafure (MR) goats. Our results revealed the highest genetic diversity in the BG goat population compared to the other goat populations. The pairwise genetic differentiation (F_ST) among the populations varied and ranged from 0.011 to 0.182, with the closest pairwise value (0.003) observed between the AB and CH goats and a distant correlation (F_ST = 0.182) between the BG and AB goats, indicating low to moderate genetic differentiation. Phylogenetic tree, ADMIXTURE and principal component analyses revealed a classification of the five Ethiopian goat breeds in accordance with their geographic distribution. We also found three top genomic regions that were detected under selection on chromosomes 2, 5 and 13. Moreover, this study identified different candidate genes related to milk characteristics (GLYCAM1 and SRC), carcass (ZNF385B, BMP-7, PDE1B, PPP1R1A, FTO and MYOT) and adaptive and immune response genes (MAPK13, MAPK14, SCN7A, IL12A, EST1 DEFB116 and DEFB119). In conclusion, this information could be helpful for understanding the genetic diversity and population structure and selection scanning of these important indigenous goats for future genetic improvement and/or as an intervention mechanism. Full article