Search Results (563)

Mastitis remains a prevalent and economically detrimental disease within the dairy industry, profoundly affecting animal welfare, milk quality, and overall production output. Nowadays, Somatic Cell Count (SCC) is widely recognized as the gold-standard indicator for the detection of mastitis; however, its limitations in pathogens discrimination and the lack of early-stage characterization of mastitis highlight the need for complementary diagnostic approaches. This review synthesizes recent research into the development and validation of novel biomarkers for the early and accurate identification of mastitis in dairy cows. The investigation encompasses a range of biological molecules for improving mastitis diagnosis. Biomarkers such as lactoferrin (LTF), β-defensin 4 (DEFB4), vitronectin, paraoxonase 1 (PON1), and N-acetyl-β-D-glucosaminidase (NAGase) show promise in distinguishing between cows not susceptible and cows susceptible to mastitis. Concurrently, nucleic acid-based biomarkers are emerging as a particularly promising frontier. While mitochondrial DNA (mtDNA) has demonstrated insufficient specificity, microRNAs (miRNAs) are gaining attention as highly stable and sensitive indicators of intramammary inflammation, potentially enabling the detection of subclinical infections before they become clinically apparent. Despite these advances, significant challenges related to specificity, reliability, and cost-effectiveness currently hinder the widespread practical application of any single biomarker. Therefore, future research should be directed towards the validation of a synergistic panel of multiple biomarkers to improve mastitis management in dairy cow farms. Full article

Diabetes mellitus (DM) leads to renal damage through oxidative stress. Carvacrol (CAR), a monoterpenoid phenol, possesses anti-inflammatory and antioxidant properties. We investigated the potential effects of CAR on histological, gene expression, and biochemical parameters in a rat model of DM. Four groups were created: group 1, control; group 2 (n = 9), DM; group 3 (n = 9), DM + dimethyl sulfoxide (DMSO); and group 4 (n = 9), DM + CAR. DM was created by injecting streptozotocin (STZ). CAR (20 mg/kg) was prepared through dissolution in 0.1% DMSO. CAR and 0.1% DMSO were administered daily for 4 weeks to groups 4 and 3, respectively. At the end of this study, urea, creatinine, paraoxonase-1 (PON-1), and arylesterase (ARES) were measured in serum samples. Histopathological changes and expression of Nuclear factor erythroid 2–related factor 2 (Nrf-2) in renal tissues were assessed. Immunohistochemical(ihc) staining and RT-qPCR analysis were performed to evaluate apoptosis, focusing on Bax and Bcl-2gene expression. Masson’s trichrome(MT) staining and RT-qPCR analysis of COL1A1 and COL3A1 mRNA levels were used to assess fibrosis. Increased urea and creatinine levels in DM were significantly decreased after CAR administration. CAR application also improved reduced levels of PON 1 and ARES, which are associated with diabetes. Both immunohistochemistry and RT-qPCR analyses revealed that CAR therapy mitigated the diabetes-induced elevation in Bax and reduction in Bcl-2 expression. CAR treatment improved histopathological findings and renal Nrf-2 immunofluorescence(if) intensity. Furthermore, gene expression analysis demonstrated that COL1A1 and COL3A1 were upregulated in DM, while CAR administration downregulated them. In conclusion, CAR has a protective role in decreasing renal impairment linked to DM by regulating Bax and Bcl-2 levels and rectifying histological damage. Full article

The practical deployment of Orthogonal Frequency Division Multiplexing Passive Optical Networks (OFDM-PONs) is hindered by the lack of a Medium Access Network (MAC) protocol capable of managing their flexible, distance-dependent data rates, despite their high spectral efficiency. This paper proposes and validates a novel rate-adaptive, Time Division Multiplexing (TDM)-based MAC protocol for OFDM-PON systems. A key contribution is the design of a three-layer header frame structure that supports multi-ONU data scheduling with heterogeneous rate profiles. Furthermore, the protocol incorporates a unique channel probing mechanism to dynamically determine the optimal transmission rate for each Optical Network Unit (ONU) during activation. The proposed Optical Line Terminal (OLT) side MAC protocol has been fully implemented in hardware on a Xilinx VCU118 FPGA platform, featuring a custom-designed ring buffer pool for efficient multi-ONU data management. Experimental results demonstrate robust upstream and downstream data transmission and confirm the system’s ability to achieve flexible net data rate switching on the downlink from 8.1 Gbit/s to 32.8 Gbit/s, contingent on the assigned rate stage. Full article

Background and Objectives: The objective of this study is to assess the efficacy of a novel software risk score, PulsIn, in predicting cardiovascular diseases within an independent study conducted on subjects from the western region of Romania. Accurate prediction of cardiovascular events in hypertensive patients remains challenging when relying solely on traditional risk scores. This study proposes PulsIn, a composite risk score that integrates classical, echocardiographic, inflammatory, renal, and metabolic markers, combined with machine learning, to refine cardiovascular risk stratification. Materials and Methods: In a prospective cohort of 300 hypertensive adults without prior major cardiovascular events, we collected demographic and clinical data, standard risk factors, laboratory biomarkers (including homocysteine, paraoxonase-1 activity, microalbuminuria, and lipid profile), and advanced echocardiographic parameters (3D left ventricular ejection fraction, diastolic function, global longitudinal strain, and left atrial strain). PulsIn was constructed as an extended composite score and used as input to machine learning models (random forest, XGBoost, and other tree-based algorithms) to predict incident major cardiovascular events. Model performance was assessed by receiver operating characteristic curves, discrimination, calibration, and feature importance and compared with established risk scores (SCORE2, Framingham, QRISK, and others). Results: PulsIn-based models showed improved predictive performance compared with traditional scores, with XGBoost and random forest achieving area under the curve values up to approximately 0.85–0.88, versus 0.60–0.78 for conventional scores. Echocardiographic indices of subclinical cardiac damage, microalbuminuria, homocysteine, and paraoxonase-1 activity emerged as key predictors, particularly enhancing reclassification in patients at intermediate risk by traditional tools. Conclusions: The PulsIn composite risk score, integrating multimodal clinical, echocardiographic, and biomarker data within a machine learning framework, offers more accurate cardiovascular risk prediction than conventional algorithms in hypertensive patients. External validation in larger, independent, and more diverse populations is required before routine clinical implementation. Full article

Background: Infections caused by the multidrug-resistant pathogen Mycobacterium abscessus (Mab) are notoriously difficult to treat. The novel β-lactamase inhibitor durlobactam, in combination with β-lactams, shows potent bactericidal activity against Mab, but the potential for acquired resistance remains a clinical concern. Objectives: To identify and characterize mechanisms of acquired resistance to durlobactam in Mab. Methods: In vitro single-step resistance selection was performed by plating wild-type Mab ATCC 19977 and by transcriptional silencing using a CRISPR interference (CRISPRi) system. Minimum inhibitory concentrations (MICs) were determined by both an agar-based method and broth microdilution. Results: Whole-genome sequencing of durlobactam-resistant mutants identified loss-of-function mutations in ponA1, a gene encoding a class A penicillin-binding protein involved in cell wall synthesis. Targeted deletion of ponA1 (ΔponA1) and CRISPRi-mediated knockdown of ponA1 expression both recapitulated the resistance phenotype, resulting in a significant increase in the durlobactam MIC on solid agar media. Strikingly, broth microdilution MICs remained largely unaffected. Conclusions: Inactivation of the peptidoglycan synthase PonA1 is a novel mechanism of resistance to durlobactam in Mab that is phenotypically expressed only during growth on solid surfaces. This finding identifies a specific genetic pathway for resistance and highlights that standard broth-based susceptibility testing could miss clinically relevant resistance mechanisms. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) commonly coexists with type 2 diabetes (T2D), but their independent contributions to redox imbalance, inflammation and immune signaling remain uncertain. Objectives: This study aimed to evaluate whether the presence of MASLD alone, and the presence of T2D within MASLD, are independently associated with high-risk profiles of oxidative/antioxidant markers, peripheral blood mononuclear cell (PBMC) gene expression and adipocytokines. Methods: A total of 190 participants were categorized via abdominal ultrasound as controls (n = 46), MASLD (n = 83) or MASLD with T2D (n = 61). Measurements included advanced oxidation protein products (AOPP) and paraoxonase-1 (PON1) activity in serum; messenger ribonucleic acids expression of cluster of differentiation 36 (CD36), Toll-like receptor 9 (TLR9), and glutathione peroxidase-1 in PBMC; and adiponectin, leptin, and resistin in plasma. Biomarker values were adjusted and statistical comparisons among groups were performed using the Quade test. Subsequently, biomarkers were stratified into tertiles to examine associations between high-risk biomarker levels and the presence of MASLD or T2D in patients with MASLD using multivariate binary logistic regression. Results: Multivariate analysis showed that MASLD presence was independently associated with both increased AOPP and decreased resistin levels in the circulation. Furthermore, T2D presence in patients with MASLD was independently associated with increased CD36 and decreased TLR9 gene expression in PBMCs, as well as elevated circulating leptin levels. Conclusions: Collectively, these findings underscore the complex interplay between oxidative stress, insulin resistance, inflammation, and immune signaling in the pathogenesis of MASLD, which are fundamental factors contributing to this condition. Full article

Accurate satellite retrieval of oceanic particulate organic nitrogen (PON) vertical profile is essential for understanding global biogeochemical processes; however, no dedicated retrieval models currently exist. This study developed a novel PON profile retrieval model using the eXtreme Gradient Boosting (XGBoost) algorithm, based on a comprehensive global dataset that includes in situ PON measurements, MODIS-Aqua bio-optical data, and 3D reanalysis physical data. The XGBoost-retrieved PON profiles were compared with those derived from Copernicus particulate backscattering coefficient ($b_{\mathit{bp}}$) profiles and were further used to estimate the euphotic-zone PON stocks through an optimally performing regression model. The results showed that the proposed model significantly outperformed models constructed without physical inputs, achieving $R^2$ of 0.83, RMSE of 1.49 $\mathrm{mg} {\mathrm{m}}^{-3}$ and MAPE of 18.07%. Compared to the $b_{\mathit{bp}}$-based profiles, the XGBoost-retrieved profiles exhibited higher accuracy. The model also provided reliable estimates of euphotic-zone PON stocks, with $R^2$ of 0.76, RMSE of 200.31 mg ${\mathrm{m}}^{-2}$ and MAPE of 15.09%. These findings demonstrate the potential of the proposed retrieval model for investigating oceanic nitrogen dynamics and biogeochemical cycles. Full article

The advent of sixth-generation (6G) communications envisions a paradigm of ubiquitous intelligence and seamless physical–digital fusion, demanding unprecedented performance from the optical transport infrastructure. Achieving terabit-per-second capacities, microsecond latency, and nanosecond synchronisation precision requires a convergent, flexible, open, and AI-native x-Haul architecture that integrates communication with distributed edge computing. This study conducts a systematic literature review of recent advances, challenges, and enabling optical technologies for intelligent and autonomous 6G networks. Using the PRISMA methodology, it analyses sources from IEEE, ACM, and major international conferences, complemented by standards from ITU-T, 3GPP, and O-RAN. The review examines key optical domains including Coherent PON (CPON), Spatial Division Multiplexing (SDM), Hollow-Core Fibre (HCF), Free-Space Optics (FSO), Photonic Integrated Circuits (PICs), and reconfigurable optical switching, together with intelligent management driven by SDN, NFV, and Artificial Intelligence/Machine Learning (AI/ML). The findings reveal that achieving 6G transport targets will require synergistic integration of multiple optical technologies, AI-based orchestration, and nanosecond-level synchronisation through Precision Time Protocol (PTP) over fibre. However, challenges persist regarding scalability, cost, energy efficiency, and global standardisation. Overcoming these barriers will demand strategic R&D investment, open and programmable architectures, early AI-native integration, and sustainability-oriented network design to make optical fibre a key enabler of the intelligent and autonomous 6G ecosystem. Full article

This study evaluates the performance of a hybrid passive optical network–radio over fiber (PON–RoF) architecture for long-term evolution (LTE)-based video transmission, focusing on the analysis of the block error rate (BLER) with and without an external RF amplifier. The results show that removing it improves receiver sensitivity by 4.04 dB in the optical link and 16 dB in the hybrid RoF link. The internal gain control of the USRP-2944R (Universal Software Radio Peripheral) is sufficient for signal processing without saturating the receiver. Furthermore, the received power levels are consistent with typical GPON sensitivity and overload ranges reported in standards, although the experimental setup corresponds to a continuous point-to-point laboratory link rather than a full GPON burst-mode configuration. Full article

Cuban sugarcane wax alcohol (policosanol) is a blend of eight characteristic aliphatic alcohols extracted from the Cuban sugarcane and widely recognized for its multifunctional applications and therapeutic properties. In the present study, the potency of policosanol (POL) was assessed for its ability to prevent metabolic stress and associated disorders posed by a high-cholesterol (HC) and high-galactose (HG) diet in zebrafish (Danio rerio). Adult zebrafish (n = 56/group) were fed either with an HC+HG diet (containing 4%, w/w cholesterol and 30%, w/w galactose), or an HC+HG amalgamated diet with POL (final 0.1% w/w or 0.5% w/w). Zebrafish in the specified groups were sacrificed post-30 weeks of feeding, and blood and organs (liver, brain, and eyes) were processed for biochemical, histological, and immunohistochemical (IHC) analysis. After 30 weeks of feeding, the highest mortality (12.5%) was noticed in the HC+HG supplement group, which was reduced to 4.5% with co-supplementation of POL (0.1% and 0.5%). In a dose-dependent manner, POL significantly reversed HC+HG elevated levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), glucose, and malondialdehyde (MDA), while substantially augmenting plasma high-density lipoprotein cholesterol (HDL-C), sulfhydryl content, ferric ion reduction ability (FRA), and paraoxonase (PON) activity. In addition, POL mitigated HC+HG-induced hepatomegaly, inflammation, and fatty liver changes. Consistently, POL minimizes ROS generation and cellular senescence in the brain and substantially improves HC+HG-induced cognitive changes (cessation of swimming ability and motion), with a marked ~5 times higher swimming distance. Notably, POL mitigated the HC+HG-induced corneal opacity and attenuated oxidative stress, apoptosis, 4-hydroxynonenal (4-HNE) accumulation, and myelin sheath degeneration in the retina. The findings underscore the therapeutic potential of policosanol in attenuating oxidative stress, metabolic changes, and various organ damage caused by prolonged exposure to the HC+HG diet. Full article

For the first time, a highly energy-efficient 32-parallel 64-point FFT scheme for IMDD OFDM-PON is proposed and implemented on a Xilinx ML605 platform. By experimentally verifying the power consumption model for the FPGA logic resources utilized in the FFT, the relationship between FFT calculating consumption and FPGA logic resource usage is established. Based on this relationship, we derive a resource selection principle for the FFT bit resolution optimization to minimize power consumption under different levels of received optical power. Consequently, the proposed FFT achieves a 76.1% reduction in power consumption compared to the traditional Spiral FFT at a received optical power of −21 dBm. Based on the proposed FFT, the real-time OFDM-PON receiver power consumption can save up to 43% compared with traditional OFDM-PON system. Full article

Background/Objectives: Ponatinib (PON) is a potent anticancer drug widely used to treat chronic myeloid leukemia (CML). Although many cancer survivors benefit from such therapies, managing drug-induced side effects, especially cardiotoxicity, remains a major challenge. Despite its prevalence, the exact mechanisms underlying PON-induced cardiotoxicity have not been thoroughly investigated. Additionally, the potential of Bone Morphogenetic Protein 7 (BMP-7) to alleviate these cardiotoxic effects has yet to be explored. Methods: To address these essential questions, we conducted a study using C57BL/6 mice. Mice were treated with PON (25 mg/kg cumulative dosage) or a combination of PON and BMP-7 (600 μg/kg), alongside a suitable control group. Heart function was assessed by echocardiography. Different techniques were performed to evaluate the apoptotic pathway. Histological staining was performed to investigate structural changes. Results: PON treatment increased apoptotic cell death (increased expression of BAX and caspase-3) in the heart through the PTEN/Akt signaling pathway. Further, PON treatment led to increased cardiac hypertrophy, adverse remodeling, and reduced cardiac function. Importantly, BMP-7 markedly reduced PON-induced apoptosis (increased Bcl2 expression) and its downstream effects. Conclusions: These results suggest that BMP-7 might inhibit PON-induced cardiotoxicity. Furthermore, our findings pave the way for future translational studies with BMP-7, which can demonstrate the therapeutic potential of BMP-7 in a clinical setting. Full article

Background and Objectives: Multiple myeloma (MM) remains an incurable plasma cell malignancy with heterogeneous clinical outcomes. Although current prognostic systems integrate biochemical and cytogenetic parameters, they do not fully capture disease complexity. Adipocytes within the bone marrow microenvironment secrete adipokines that regulate inflammation, metabolism, and immune interactions and may influence disease progression. This study aimed to assess circulating adipokines and related microenvironmental mediators as potential biomarkers of disease activity and treatment response in MM. Materials and Methods: In this case–control, cross-sectional study, the serum levels of eight adipokine-related molecules—adiponectin, leptin, resistin, chemerin, adipsin, thrombospondin-1 (TSP-1), paraoxonase-1 (PON-1), and myeloperoxidase (MPO)—were measured in 40 MM patients and 38 age- and sex-matched healthy controls. Enzyme-linked immunosorbent assays (ELISA) and bead-based multiplex immunoassays were used. Associations with prognostic markers (serum β₂-microglobulin (sB2M), LDH, albumin, hemoglobin, renal function) and treatment response were analyzed using correlation and non-parametric statistical methods. Results: Compared to the controls, MM patients exhibited significantly higher circulating levels of adiponectin, resistin, chemerin, adipsin, TSP-1, and MPO, while leptin was decreased. Among clinical correlations, chemerin and PON-1 correlated positively with sB2M, TSP-1 correlated with LDH, and MPO correlated with M-protein and albumin. Resistin was lower in patients with renal impairment and an advanced disease stage. Adiponectin and TSP-1 were significantly lower in progressive disease compared to complete remission, suggesting their potential association with treatment response. Conclusions: This study demonstrates that multiple adipokines are dysregulated in MM and exhibit distinct associations with disease burden, renal function, and therapeutic response. Novel associations identified for TSP-1, PON-1, and adipsin highlight previously unrecognized microenvironmental pathways in MM biology. Adipokine profiling may complement established prognostic markers and provide new insights into the tumour microenvironment in MM. Full article

The Paraoxonase (PON) gene family consists of three paralogues (PON1, PON2 and PON3) that are tandemly located on chromosome 7. In this review paper, the structure and function of the encoded proteins is summarized. In addition, an overview is given on the generated animal models. Finally, their involvement in the pathogenesis of different diseases is discussed, starting from an extended screening of the literature using PUBMED and Web of Science. PON1 and PON3 are mainly expressed in the liver and released into the bloodstream, bound to high-density lipoprotein. PON2 is expressed in various tissues, including the liver, lungs, heart, placenta and testes, but remains intracellular. The name of the enzyme family reflects PON1′s ability to neutralize paraoxon, but they also exhibit lactonase and esterase activities. All three PON enzymes play a role in reducing lipid peroxides in High-Density Lipoproteïne (HDL) and low-density lipoprotein(LDL), giving them antioxidant properties. This links them to Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD), a metabolic liver condition marked by the excessive accumulation of triglycerides (TG) in liver cells. In addition to their association with MASLD, the PON genes are, due to their antioxidant properties, also associated with other conditions including cardiovascular diseases, chronic kidney disease, neurological and immunological conditions up to some forms of cancer. In the latter, the antioxidant properties can result in tumor progression by protecting malignant cells from oxidative damage thus supporting survival, proliferation and metastasis indicating them as potential drug targets for treatment of cancer. Therefore, further research on this protein family can provide novel insights into their function and their potential therapeutic applicability. Full article

Wavelength Division Multiplexing-based Passive Optical Networks (WDM-PONs) are among the most advanced optical networks without active elements, using a wide range of wavelengths to increase network reliability, scalability, and capacity. This ensures the provision of high quality, fast, and available services for end users. In this aim, traffic protection considerations have markedly enhanced their role. Traffic protection schemes can be divided into Point-To-MultiPoint (P2MP) and ring architectures. Traffic protection scenarios of access WDM-PONs in the P2MP architecture include Type B, dual-parented Type B, and Type C, while the ring architecture includes protected access and metropolitan-access WDM-PONs. Any potential traffic protection scheme can be represented by a corresponding reliability block diagram for the purpose of cost–benefit analysis. An important aspect of the WDM-PON design is presented by the Capital (CAPEXs) and Operational (OPEXs) Expenditures, which play a key role in network optimization. Managing them efficiently allows us to achieve an economically sustainable and efficient infrastructure of future passive optical networks involving traffic protection schemes. In this work, we focused on simulation model development for calculating the CAPEX and OPEX costs and the subsequent cost–benefit analysis of possible WDM-PON traffic protection schemes. Full article