Search Results (21)

Garlic (Allium sativum L.) cultivars in Korea, particularly the widely adaptable ‘Hongsan’, are challenging to identify in processed forms or seedlings due to the plasticity of phenotypic traits such as clove tip greening. This uncertainty increases the risk of mislabeling and the infringement of breeders’ rights under the UPOV framework. This study aimed to develop a stable SCAR marker for ‘Hongsan’-specific identification using a RAPD-based DNA pooling method. Sixty Operon primers (>60% GC) were screened against ‘Hongsan’ gDNA versus a multi-cultivar DNA pool (‘Daeseo’, ‘Uiseong’, ‘Danyang’, and ‘Namdo’); OPE-01 consistently amplified a unique 1.3 kb band, which was cloned and sequenced, revealing a 1272 bp sequence with a translocation junction (878 + 394 bp), a 18 bp insertion, and an EcoRI site on chromosome 2 (NCBI reference sequence: GCA_030737875.1). SCAR primers SaH191R/SaH513F produced a specific 545 bp amplicon in Hongsan, clearly distinguishing it from other cultivars and parental lines, indicating that the marker locus is related to the paternal line ‘9209’. This RAPD-to-SCAR marker overcomes reproducibility limitations and enables reliable authentication of Hongsan in processing powders and black garlic irrespective of environmental factors. This cost-effective and rapid assay ensures industry transparency, quality control, and IP protection for Korean garlic production. Full article

To address the rigorous requirements of ultra-reliable low-latency communication (URLLC) in beyond 5G/6G networks, we propose an innovative architecture combining automatic repeat request (ARQ) protocol with a simultaneously transmitting and reflecting reconfigurable intelligent surface (STAR-RIS) to enhance short-packet non-orthogonal multiple access (NOMA) communications. Specifically, retransmission mechanism provided by ARQ is utilized to mitigate packet errors stemming from practical system imperfections, i.e., imperfect channel state information (ipCSI), imperfect successive interference cancellation (ipSIC), and hardware impairments. Using the analytical foundation provided by finite blocklength (FBL) theory, expressions for two key performance metrics, i.e., the average block error rate (BLER) and effective throughput, are derived for two NOMA users. Simulation results validate the analytical derivations and demonstrate that the ARQ scheme provides significant reliability gains for each user and achieves synergistic gain with STAR-RIS technology. In addition, the effective throughput exhibits a peak at an optimal blocklength, balancing the reliability gain from a longer blocklength against the spectral efficiency loss from a lower coding rate. This optimal blocklength decreases with more STAR-RIS elements, as improved channel conditions reduce the need for long blocklengths. Full article

WIB-801CE, a standardized Cordyceps militaris extract containing 7.0% cordycepin, suppresses platelet activation induced by thrombin, collagen, and adenosine diphosphate (ADP). As these agonists generate thromboxane A₂ (TXA₂), which amplifies platelet activation via a self-propagating feedback loop, blockade of TXA₂-mediated signaling offers strong antithrombotic potential. TXA₂-antagonistic effects were evaluated using U46619, a stable TXA₂ analog. Platelet activation was assessed by fibrinogen binding to integrin αIIbβ₃, aggregation, and phosphorylation of platelet-activating proteins—PI3K (Tyr458), Akt (Ser473), p38 MAPK (Thr180/Tyr182), ERK1 (Thr202/Tyr204), JNK1 (Thr183/Tyr185)—and inhibitory proteins—VASP (Ser157) and IP₃RI (Ser1756)—via immunoblotting. Thrombin-induced fibrin clot retraction, cytotoxicity, coagulation parameters, and antioxidant capacity were also examined. WIB-801CE significantly inhibited U46619-induced fibrinogen binding to integrin αIIbβ₃ and platelet aggregation, without inducing cytotoxicity or impairing hemostatic function. It also significantly downregulated the phosphorylation of platelet-activating proteins and upregulated the phosphorylation of platelet-inhibiting proteins. Additionally, WIB-801CE abolished thrombin-induced fibrin clot retraction and demonstrated antioxidant capacity. WIB-801CE disrupts TXA₂-driven platelet activation and thrombus stabilization by selectively modulating phosphorylation of key signaling proteins at defined regulatory sites. These properties highlight its promise as a therapeutic candidate for thrombotic disorders with platelet hyperreactivity. Full article

Seed vigor is a key agronomic trait that integrates germination capacity and seedling establishment, critically influencing rice productivity. Inositol hexakisphosphate (IP₆) serves as a major phosphorus reservoir in seeds, yet its regulatory mechanism in seed vigor remains unclear. Here, we demonstrate that exogenous IP₆ application inhibited seed germination and seedling growth of japonica rice (Oryza sativa L. ssp. japonica cv. Zhonghua11) in a dose-dependent manner; 10 mM IP₆ reduced seed germination by 100%, while 100 μM IP₆ suppressed primary root length by 33.6% compared to the control. This inhibitory effect is likely mediated by antagonizing auxin signaling, as supported by suppressed DR5::GUS expression and altered transcription of auxin-responsive genes. OsIPK2, a key enzyme in IP₆ biosynthesis, showed high expression during early development in rice. RNA interference of OsIPK2 led to a 40.8–61.7% reduction in seed IP₆ content, 45.3–65% higher zinc (Zn) and iron (Fe) accumulation, and a 35.4–53.5% lower germination rate compared to wild-type (WT). Conversely, OsIPK2-RNAi seedlings exhibited enhanced growth and resistance to IP₆, which was associated with misregulation of auxin-responsive genes and a decrease in the repressive histone mark H3K27me3 at their loci. Furthermore, endogenous indole-3-acetic acid (IAA) levels significantly reduced in Ri-1 but unchanged in Ri-2, while abscisic acid (ABA) content and the IAA/ABA ratio remained unaltered compared to wild-type. Our findings reveal that OsIPK2 balances seed vigor and seedling development by modulating inositol phosphate metabolism, auxin responses, and epigenetic regulation, providing insights for improving seed quality in cereals. Whether the regulatory role of OsIPK2 in seed vigor is conserved across other rice subspecies requires further investigation. Full article

Livestock is the backbone of the economy in an agricultural country like Pakistan, with cattle serving as a milk and protein source. In 2021/22, Pakistan was hit by the first major outbreak of lumpy skin disease (LSD) in cattle, in all four provinces. LSD is characterized by the development of skin nodules, leading to severe illness, decreased milk production, and mortality, causing huge economic losses. This study aimed to analyze and classify the lumpy skin disease virus (LSDV) strains involved in the outbreak in the Punjab province at the molecular and phylogenetic levels to develop effective control strategies. A combination of different real-time PCRs was used for the identification and differentiation between vaccine, wild-type, and recombinant LSDV strains. This was mented with the sequence determination and phylogenetic analysis of ten genomic loci from two selected isolates from the 2021/22 Pakistan outbreak. The combined data showed that these isolates belonged to LSDV clade 1.2 and were clearly different from the vaccine clade 1.1 (Neethling-like), as well as from the recombinant clade 2 strains. In addition, using a fit-for-purpose gel-based PCR, the isolates from the outbreak were also shown to be different from KSGP0240-based vaccines. Full article

Bark beetle-associated bacteria from the sub-boreal and boreal forests of northern Canada represent a largely unexplored source of bioactive natural products. This study aims to investigate the chemical potential of bacteria isolated from Dendroctonus ponderosae, Dendroctonus rufipennis, Dendroctonus pseudotsugae, and Ips perturbatus by focusing on nitrogen-containing secondary metabolites. Genomic analyses of the bacterial isolates identified diverse biosynthetic gene clusters (BGCs), including nonribosomal peptides (NRPs), NRPS-PKS hybrids, and ribosomally synthesized and post-translationally modified peptides (RiPPs), many of which exhibit low sequence homology, suggesting potential for novel bioactive compounds. Nitrogen-15 NMR spectroscopy was employed to detect nitrogen-containing functional groups in crude extracts, revealing distinct signals for amides, amines, and nitrogen heterocycles. The combination of BGC predictions and NMR data highlighted the genetic and chemical diversity of these bacteria and underscored the potential for discovering novel nitrogen-rich metabolites. These findings provide a foundation for further exploration of bioactive natural products with pharmaceutical and agrochemical applications and potential to contribute to the understanding of the chemical ecology of bark beetle–microbe interactions in northern ecosystems. Full article

Recently, there has been an explosive growth in wireless devices capable of connecting to the Internet and utilizing various services anytime, anywhere, often while on the move. In the realm of the Internet, such devices are called mobile nodes. When these devices are in motion or traverse different domains while communicating, effective mobility management becomes essential to ensure the continuity of their services. Software-defined networking (SDN), a new paradigm in networking, offers numerous possibilities for addressing the challenges of mobility management. By decoupling the control and data planes, SDN enables greater flexibility and adaptability, making them a powerful framework for solving mobility-related issues. However, communication can still be momentarily disrupted due to frequent changes in IP addresses, a drop in radio signals, or configuration issues associated with gateways. Therefore, this paper introduces Routage Inter-domains in SDN (RI-SDN), a novel anchor-based routing method designed for inter-domain mobility in SDN architectures. The method identifies a suitable anchor domain, a critical intermediary domain that contributes to reducing delays during data transfer because it is the closest domain (i.e., node) to the destination. Once the anchor domain is identified, the best routing path is determined as the route with the smallest metric, incorporating elements such as bandwidth, flow operations, and the number of domain hops. Simulation results demonstrate significant improvements in data transfer delay and handover latency compared to existing methods. By leveraging SDN’s potential, RI-SDN presents a robust and innovative solution for real-world scenarios requiring reliable mobility management. Full article

Cellular reprogramming of somatic cells towards induced pluripotency is a multistep stochastic process mediated by the transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM), which orchestrate global epigenetic and transcriptional changes. We performed a large-scale analysis of integrated ChIP-seq, ATAC-seq and RNA-seq data and revealed the spatiotemporal highly dynamic pattern of OSKM DNA binding during reprogramming. We found that OSKM show distinct temporal patterns of binding to different classes of pluripotency-related enhancers. Genes involved in reprogramming are regulated by the coordinated activity of multiple enhancers, which are sequentially bound by OSKM for strict transcriptional control. Based on these findings, we developed an unbiased approach to identify Reprogramming-Inducible Enhancers (RIEs), constructed enhancer-traps and isolated cells undergoing reprogramming in real time. We used a representative RIE taken from the Upp1 gene fused to Gfp and isolated cells at different time-points during reprogramming and found that they have unique developmental capacities as they are reprogrammed with high efficiency due to their distinct molecular signatures. In conclusion, our experiments have led to the development of an unbiased method to identify and isolate reprogrammable cells in real time by exploiting the functional dynamics of OSKM, which can be used as efficient reprogramming biomarkers. Full article

For the future of sixth-generation (6G) wireless communication, simultaneously transmitting and reflecting reconfigurable intelligent surface (STAR-RIS) technology is emerging as a promising solution to achieve lower power transmission and flawless coverage. To facilitate the performance analysis of RIS-assisted networks, the statistics of the sum of double random variables, i.e., the sum of the products of two random variables of the same distribution type, become vitally necessary. This paper applies the statistics of the sum of double random variables in the performance analysis of an integrated power beacon (PB) energy-harvesting (EH)-based NOMA-assisted STAR-RIS network to improve its outage probability (OP), ergodic rate, and average symbol error rate. Furthermore, the impact of imperfect successive interference cancellation (ipSIC) on system performance is also analyzed. The analysis provides the closed-form expressions of the OP and ergodic rate derived for both imperfect and perfect SIC (pSIC) cases. All analyses are supported by extensive simulation results, which help recommend optimized system parameters, including the time-switching factor, the number of reflecting elements, and the power allocation coefficients, to minimize the OP. Finally, the results demonstrate the superiority of the proposed framework compared to conventional NOMA and OMA systems. Full article

Objectives: The term “inflammageing” describes the process of inflammation-induced aging that leads living cells to a state of permanent cell cycle arrest due to chronic antigenic irritation. This in vitro study aimed to shed light on the mechanisms of “inflammageing” on human oral cells. Methods: Primary cultures of human gingival fibroblasts (hGFs) were exposed to variable pro-inflammatory stimuli, including lipopolysaccharide (LPS), Tumor Necrosis Factor-alpha (TNFa), and gingival crevicular fluid (GCF) collected from active periodontal pockets of systemically healthy patients. Inflammageing was studied through two experimental models, employing either late-passage (“aged”) cells (p. 10) that were exposed to the pro-inflammatory stimuli or early-passage (“young”) cells (p. 1) continuously exposed during a period of several passages (up to p. 10) to the above-mentioned stimuli. Cells were evaluated for the expression of beta-galactosidase activity (histochemical staining), senescence-associated genes (qPCR analysis), and biomarkers related to a Senescence-Associated Secretory Phenotype (SASP), through proteome profile analysis and bioinformatics. Results: A significant increase (p < 0.05) in beta-galactosidase-positive cells was observed after exposure to each pro-inflammatory stimulus. The senescence-associated gene expression included upregulation for CCND1 and downregulation for SUSD6, and STAG1, a profile typical for cellular senescence. Overall, pro-inflammatory priming of late-passage cells caused more pronounced effects in terms of senescence than long-term exposure of early-passage cells to these stimuli. Proteomic analysis showed induction of SASP, evidenced by upregulation of several pro-inflammatory proteins (IL-6, IL-10, IL-16, IP-10, MCP-1, MCP-2, M-CSF, MIP-1a, MIP-1b, TNFb, sTNF-RI, sTNF-RII, TIMP-2) implicated in cellular aging and immune responses. The least potent impact on the induction of SASP was provoked by LPS and the most pronounced by GCF. Conclusion: This study demonstrates that long-term exposure of hGFs to various pro-inflammatory signals induced or accelerated cellular senescence with the most pronounced impact noted for the late-passage cells. The outcome of these analyses provides insights into oral chronic inflammation as a potential confounder of age-related diseases. Full article

Radiation injury- and radiation combined with skin injury-induced inflammatory responses in the mouse brain were evaluated in this study. Female B6D2F1/J mice were subjected to a sham, a skin wound (SW), 9.5 Gy ⁶⁰Co total-body gamma irradiation (RI), or 9.5 Gy RI combined with a skin puncture wound (RCI). Survival, body weight, and wound healing were tracked for 30 days, and mouse brain samples were collected on day 30 after SW, RI, RCI, and the sham control. Our results showed that RCI caused more severe animal death and body weight loss compared with RI, and skin wound healing was significantly delayed by RCI compared to SW. RCI and RI increased the chemokines Eotaxin, IP-10, MIG, 6Ckine/Exodus2, MCP-5, and TIMP-1 in the brain compared to SW and the sham control mice, and the Western blot results showed that IP-10 and p21 were significantly upregulated in brain cells post-RI or -RCI. RI and RCI activated both astrocytes and endothelial cells in the mouse brain, subsequently inducing blood–brain barrier (BBB) leakage, as shown by the increased ICAM1 and GFAP proteins in the brain and GFAP in the serum. The Doublecortin (DCX) protein, the “gold standard” for measuring neurogenesis, was significantly downregulated by RI and RCI compared with the sham group. Furthermore, RI and RCI decreased the expression of the neural stem cell marker E-cadherin, the intermediate progenitor marker MASH1, the immature neuron cell marker NeuroD1, and the mature neuron cell marker NeuN, indicating neural cell damage in all development stages after RI and RCI. Immunohistochemistry (IHC) staining further confirmed the significant loss of neural cells in RCI. Our data demonstrated that RI and RCI induced brain injury through inflammatory pathways, and RCI exacerbated neural cell damage more than RI. Full article

The inositol triphosphate-associated proteins IRAG1 and IRAG2 are cGMP kinase substrate proteins that regulate intracellular Ca²⁺. Previously, IRAG1 was discovered as a 125 kDa membrane protein at the endoplasmic reticulum, which is associated with the intracellular Ca²⁺ channel IP₃R-I and the PKGIβ and inhibits IP₃R-I upon PKGIβ-mediated phosphorylation. IRAG2 is a 75 kDa membrane protein homolog of IRAG1 and was recently also determined as a PKGI substrate. Several (patho-)physiological functions of IRAG1 and IRAG2 were meanwhile elucidated in a variety of human and murine tissues, e.g., of IRAG1 in various smooth muscles, heart, platelets, and other blood cells, of IRAG2 in the pancreas, heart, platelets, and taste cells. Hence, lack of IRAG1 or IRAG2 leads to diverse phenotypes in these organs, e.g., smooth muscle and platelet disorders or secretory deficiency, respectively. This review aims to highlight the recent research regarding these two regulatory proteins to envision their molecular and (patho-)physiological tasks and to unravel their functional interplay as possible (patho-)physiological counterparts. Full article

The global targeted disruption of the natriuretic peptide receptor-A (NPRA) gene (Npr1) in mice provokes hypertension and cardiovascular dysfunction. The objective of this study was to determine the mechanisms regulating the development of cardiac fibrosis and dysfunction in Npr1 mutant mice. Npr1 knockout (Npr1^−/−, 0-copy), heterozygous (Npr1^+/−, 1-copy), and wild-type (Npr1^+/+, 2-copy) mice were treated with the transforming growth factor (TGF)-β1 receptor (TGF-β1R) antagonist GW788388 (2 µg/g body weight/day; ip) for 28 days. Hearts were isolated and used for real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical analyses. The Npr1^−/− (0-copy) mice showed a 6-fold induction of cardiac fibrosis and dysfunction with markedly induced expressions of collagen-1α (3.8-fold), monocyte chemoattractant protein (3.7-fold), connective tissue growth factor (CTGF, 5.3-fold), α-smooth muscle actin (α-SMA, 6.1-fold), TGF-βRI (4.3-fold), TGF-βRII (4.7-fold), and phosphorylated small mothers against decapentaplegic (pSMAD) proteins, including pSMAD-2 (3.2-fold) and pSMAD-3 (3.7-fold), compared with wild-type mice. The expressions of phosphorylated extracellular-regulated kinase ERK1/2 (pERK1/2), matrix metalloproteinases-2, -9, (MMP-2, -9), and proliferating cell nuclear antigen (PCNA) were also significantly upregulated in Npr1 0-copy mice. The treatment of mutant mice with GW788388 significantly blocked the expression of fibrotic markers, SMAD proteins, MMPs, and PCNA compared with the vehicle-treated control mice. The treatment with GW788388 significantly prevented cardiac dysfunctions in a sex-dependent manner in Npr1 0-copy and 1-copy mutant mice. The results suggest that the development of cardiac fibrosis and dysfunction in mutant mice is predominantly regulated through the TGF-β1-mediated SMAD-dependent pathway. Full article

SARS-CoV-2 is a new coronavirus characterized by a high infection and transmission capacity. A significant number of patients develop inadequate immune responses that produce massive releases of cytokines that compromise their survival. Soluble factors are clinically and pathologically relevant in COVID-19 survival but remain only partially characterized. The objective of this work was to simultaneously study 62 circulating soluble factors, including innate and adaptive cytokines and their soluble receptors, chemokines and growth and wound-healing/repair factors, in severe COVID-19 patients who survived compared to those with fatal outcomes. Serum samples were obtained from 286 COVID-19 patients and 40 healthy controls. The 62 circulating soluble factors were quantified using a Luminex Milliplex assay. Results. The patients who survived had decreased levels of the following 30 soluble factors of the 62 studied compared to those with fatal outcomes, therefore, these decreases were observed for cytokines and receptors predominantly produced by the innate immune system—IL-1α, IL-1α, IL-18, IL-15, IL-12p40, IL-6, IL-27, IL-1Ra, IL-1RI, IL-1RII, TNFα, TGFα, IL-10, sRAGE, sTNF-RI and sTNF-RII—for the chemokines IL-8, IP-10, MCP-1, MCP-3, MIG and fractalkine; for the growth factors M-CSF and the soluble receptor sIL2Ra; for the cytokines involved in the adaptive immune system IFNγ, IL-17 and sIL-4R; and for the wound-repair factor FGF2. On the other hand, the patients who survived had elevated levels of the soluble factors TNFβ, sCD40L, MDC, RANTES, G-CSF, GM-CSF, EGF, PDGFAA and PDGFABBB compared to those who died. Conclusions. Increases in the circulating levels of the sCD40L cytokine; MDC and RANTES chemokines; the G-CSF and GM-CSF growth factors, EGF, PDGFAA and PDGFABBB; and tissue-repair factors are strongly associated with survival. By contrast, large increases in IL-15, IL-6, IL-18, IL-27 and IL-10; the sIL-1RI, sIL1RII and sTNF-RII receptors; the MCP3, IL-8, MIG and IP-10 chemokines; the M-CSF and sIL-2Ra growth factors; and the wound-healing factor FGF2 favor fatal outcomes of the disease. Full article

Alterations in tear cytokine levels have been associated with various ocular disorders as compared to those in healthy subjects. However, age and sex are not always considered in these comparisons. In this study we aimed to establish age and sex reference intervals (RIs) for tear cytokine levels in healthy people. Tear samples were taken from 75 males and 82 females, aged 18–88 years, and tear cytokine levels were determined. Age- and sex-adjusted RIs for epidermal growth factor (EGF), fractalkine, interleukin (IL)-1 receptor antagonist (RA), IL-7, IL-8, interferon inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, and vascular endothelial growth factor (VEGF) tear cytokine levels in a healthy sample were established using generalized additive for location, scale and shape (GAMLSS) models. RIs were tested in two external samples: a validation sample of 40 individuals with normal results at four Dry Eye Disease (DED) clinical diagnostic tests (OSDI, T-BUT, corneal staining and Schirmer test); and a utility sample of 13 severe DED cases. IL-1RA, IL-8, IP-10, and MCP-1 levels showed a positive association with age, while EGF was negatively correlated. IL-7 concentration increased up to 40 years and again after 70 years, observing a quasi-linear decrease between them. For VEGF, higher levels were observed in the middle-aged range. Regarding sex-influence, fractalkine tear levels were higher in men, whereas those of IL-7, IL-8, and IP-10 were higher in women. Using the estimated age- and sex-adjusted RIs, more than 92% of the validation sample was correctly classified, and 100% of the severe DED patients in the utility sample had concentrations outside the RIs in at least two of the cytokines evaluated. Full article