Search Results (795)

Blood collection tubes are widely used medical devices. Inaccurate citrate anticoagulant concentration can influence the results of coagulation tests. The producer’s expertise and responsibility are considered the quality safeguards. However, the tubes undergo changes during their lifecycle, partly due to storage conditions, and the end user or a third party has no comprehensive insight. A methodology is necessary to reveal the tube’s inherent characteristics. We provide insight into the anionic–cationic composition and pH of anticoagulant solutions in commercial tubes using high-performance ion exchange chromatography on a purified water model, making the anticoagulant volume accuracy assessment possible through a direct dye-dilution method. The results revealed differences between the tubes of two producers, Greiner BIO-ONE (A and A(nr)) and BD (C). Tube C has the most accurate anticoagulant amount. Both brands contain buffered citrate. The method of buffer preparation is not a source of interferant for the spectrometric method of the tubes’ quality evaluation. Acetate, formate, chloride, nitrite, sulfate, oxalate, bromide, and nitrate impurities were determined in anticoagulant solutions, all in tube A and some in the others. Tubes C exhibit the highest contamination with cations. Full article

Alterations in the ratio of oxidized and reduced nicotinamide adenine dinucleotide (NAD⁺/NADH) reflect the intracellular redox state and have been implicated in a broad spectrum of pathological conditions, including neurogenetic disorders, heart failure, and liver diseases. In the present study, we demonstrate the selective detection of probe-derived NAD⁺ and NADH signals in mouse liver extracts by means of a triple-resonance nuclear magnetic resonance (NMR) spectroscopy technique. We prepared ¹³C/¹⁵N-enriched nicotinamide riboside (¹³C/¹⁵N-NR), which undergoes enzymatic conversion to NAD⁺ and NADH in the liver, and detected these labeled metabolites by ¹H–{¹³C–¹⁵N} triple-resonance NMR measurements. This study provides a methodological proof-of-concept for the selective detection of NAD-related signals derived from a stable-isotope labeled probe in mouse liver extracts. Full article

Background and Objectives: Diabetes mellitus (DM) is a major global health concern, with diabetes-related foot disease (DFD) representing one of its most severe complications, often resulting in chronic infection, osteomyelitis, and limb amputation. Conventional therapies frequently fail in refractory cases, necessitating novel adjunctive strategies. Ozone therapy (OT) possesses antimicrobial, immunomodulatory, and oxygen-enhancing properties, while negative pressure wound therapy (NPWT) facilitates granulation, exudate removal, and tissue perfusion. This study explored the combined efficacy of OT and NPWT in advanced DFD. Materials and Methods: An exploratory, retrospective, observational cohort study was conducted at a specialized wound care center in Gdańsk, Poland, between 2019 and 2022. The study included 30 patients (n = 30) with refractory DFD involving both soft tissue and bone infection who had not responded to previous conventional treatment. The analyzed treatment approach consisted of surgical debridement, application of topical ozonated preparations, and (NPWT) with instillation of ozonated saline administered over a six-week period. Clinical outcomes included wound healing assessed using the Wagner classification and wound volume reduction, pain intensity measured using the Numeric Rating Scale (NRS), inflammatory biomarkers (C-reactive protein [CRP] and procalcitonin [PCT]), and microbiological characteristics of wound cultures. Statistical analyses were performed using the Wilcoxon signed-rank test and the chi-square test, and regression modeling was applied to identify potential predictors of therapeutic response. Statistical significance was defined as p < 0.05. Results: By week six, 100% of ulcers improved to Wagner stage ≤1, with 26.7% achieving stage 0. Median wound volume decreased from 5.5 cm³ to 0 cm³ (p < 0.001). Pain scores declined from 7.2 ± 0.96 points to 0.2 ± 0.5 points (p < 0.001). CRP and PCT levels decreased significantly (p < 0.001), and microbiological clearance was observed in all cases. Higher body mass index (BMI) was associated with poorer pain reduction. Conclusions: The combination of standard wound care with OT and NPWT was associated with clinically relevant improvements in wound healing, infection control, systemic inflammation, and pain reduction in patients with refractory DFD. Although limited by a non-controlled design and small cohort size, these findings support further randomized controlled trials to define the role of this combined approach in integrated diabetic foot care. Full article

Background: Gestation is a period of significant biological plasticity where the intrauterine environment influences fetal development via “fetal programming”. This study systematically reviews and meta-analyzes the association between genetic determinants—specifically the NR3C1, FKBP5, and CRHR1 genes, chosen for their pivotal role in the functional regulation and feedback sensitivity of the hypothalamic–pituitary–adrenal (HPA) axis—and stress reactivity during pregnancy. Methods: Following PRISMA guidelines, a systematic search was conducted across PubMed, Scopus, and Web of Science, yielding an initial total of 1430 records. After removing duplicates and screening 669 studies, a total of 34 primary observational studies were included in the systematic review and qualitative synthesis. For the quantitative synthesis, 27 articles provided sufficient data, resulting in k = 39 independent effect sizes analyzed via a mixed-effects model to account for tissue-specific and cohort-specific outcomes. Results: Systematic analysis reveals that maternal psychosocial stress significantly correlates with NR3C1 hypermethylation, acting as a biological mediator for neonatal cortisol dysregulation and hippocampal volume reduction. The FKBP5 rs1360780 polymorphism emerged as a key moderator of structural vulnerability, showing a “double-hit” effect when combined with epigenetic alterations. Furthermore, the study identifies sex-specific susceptibility, with divergent placental trajectories for male and female fetuses. Meta-analytic estimates confirmed the robustness of these associations (Rosenthal Fail-Safe N = 431,000), despite a general trend toward statistical significance (p = 0.079) in heterogeneous cohorts. Conclusions: The findings underscore a stable link between genetic determinants and prenatal stress reactivity. The interaction between molecular predisposition and environmental factors defines the health of the mother–infant dyad. These results advocate for a transition toward Precision Prenatal Medicine, integrating polygenic risk scores and epigenetic monitoring to implement early, targeted preventive interventions. Full article

Objective: This study evaluated the relationships between the development and clinical course of pressure injuries (PIs) and neurological status, nutritional risk, and laboratory parameters among patients admitted to a tertiary intensive care unit. Materials and Methods: The single-center, retrospective, observational study included 220 patients hospitalized in the intensive care unit for at least 5 days. On the day of admission, Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II), Braden, and Nutritional Risk Screening 2002 (NRS-2002) scores were assessed. Demographic characteristics, comorbidities, need for sedation and vasopressors, and laboratory parameters during the first 24 h (albumin, C-reactive protein, lactate, D-dimer) were analyzed. Factors independently associated with new PI development and clinical improvement were identified using binary logistic regression. Results: New PIs developed in 25% of patients. Patients with PI progression were older and had lower GCS and Braden scores, higher NRS-2002 scores, lower albumin levels, and higher D-dimer levels (p < 0.05). In multivariable analysis, low GCS (OR = 0.824), presence of comorbidity (OR = 2.327), and a high NRS-2002 risk level were independent predictors of new PI development. The model’s discriminative ability was acceptable (AUC = 0.756). Among patients with existing PIs, NRS-2002 score (OR = 0.450) and age (OR = 1.058) were independently associated with clinical improvement in an exploratory multivariable model. Conclusions: NRS-2002 was the only variable independently associated with both new PI development and the clinical improvement of existing lesions, underscoring the central role of nutritional risk assessment in ICU-based PI prevention and prognosis. Full article

Background/Objectives: Catheter-related bladder discomfort (CRBD) is a common complication that patients with Foley catheters may experience following surgery. Previous studies have suggested that nefopam can reduce the incidence and severity of CRBD; however, dose-dependent effects (20 mg vs. 40 mg) have not been directly compared. Therefore, this study aimed to evaluate the dose-dependent effects of nefopam on CRBD, determine its effective dose, and assess the incidence of associated side effects. Methods: Electronic medical records of patients aged 18–70 years with American Society of Anesthesiologists physical status I–III who underwent elective transurethral ureteroscopic lithotripsy under general anesthesia from August 2016 to December 2022 were reviewed. Patients were categorized into three groups: premedication with intravenous nefopam 20 mg (group N20), premedication with nefopam 40 mg (group N40), or no premedication (control, group C). Results: The incidence rates of CRBD were 85.7% in group C, 81.3% in group N20, and 51.4% in group N40, showing a significant difference among the groups (p = 0.003, Pearson’s chi-squared test). Postoperative NRS was significantly different among the groups (p < 0.001, one-way ANOVA). In post hoc analysis, both group N20 and group N40 showed significantly lower scores compared to group C (p = 0.002, p = 0.001 respectively). The severity of CRBD also decreased in a dose-dependent manner, which was considered significant. No significant differences were observed among the groups in terms of intraoperative hemodynamic stability or postoperative nausea and vomiting. Conclusions: The administration of nefopam 40 mg significantly reduced the incidence and severity of CRBD compared with no premedication. Full article

With the rapid development of cancer treatment, immunotherapy has revolutionized renal cell carcinoma (RCC) treatment, yet patient responses remain heterogeneous. Here, a computational pipeline was constructed by integrating single-cell and bulk RNA sequencing data to identify immune-related candidate driver genes and characterize their impact on RCC immunotherapy. Based on gene regulatory networks (GRN), 25 immune-related candidate driver genes were identified, leading to the stratification of patients into three clusters (C1–C3). Compared to the C2/C3 cluster, the C1 cluster exhibited elevated immune infiltration, tumor mutation burden and checkpoint expression, which may represent immunotherapy responders. Dynamic analysis of GRNs revealed the critical role of candidate driver genes in predicting the efficacy of immunotherapy. IRF1, IRF9 and STAT1 in lymphoid cells of C1 participated in anti-tumor immune response by impacting target genes CD8A, HLA-A/E, TAP1 and PD-1. JUN, FOS, STAT3, JUND and NR2F1 were up-regulated in clusters C2 and C3, leading to tumor progression and immune evasion by influencing target genes HSPA1A, CXCL9 and PDGFR. In conclusion, integration of the transcriptome with molecular networks provided a network-based framework to uncover immune-related candidate driver genes for stratifying RCC patients, thereby serving as potential therapeutic targets to improve the outcome of RCC immunotherapy. Full article

Maternal nutrition during late gestation is critical for fetal development, neonatal resilience, and postnatal adaptation in beef cattle. This study aimed to evaluate the effects of nutritional restriction and supplementation of hydroxytyrosol (HT) in late pregnancy on behavioural, circadian, stress-related, and inflammatory responses in cows and their restricted nursed offspring. Pregnant cows were allocated to a 2 × 2 factorial experimental design (feeding level: T100% vs. T60% of nutrient requirements; HT: 0 vs. 180 mg/kg of diet). Cow behaviours were recorded during meals (from week −12 prepartum to term), and calf activities, body temperature, and mother–offspring interactions were assessed at 5 weeks postpartum. Nutritional restriction accelerated feed intake in cows and increased stress-related behaviours, while HT partially mitigated these effects. Molecular analyses in blood samples revealed dynamic prepartum upregulation of glucocorticoid-receptor NR3C1 in week −6, and downregulation of circadian (BMAL1, PER1, CRY1) gene expression in week 5 after parturition, both in T60%-HT cows. In calves, maternal HT supplementation promoted active exploratory behaviour, and counteracted behavioural and circadian (CRY1 and PER1) and inflammatory markers (IL8) gene expression resulting from prenatal nutrient restriction, leading to behavioural profiles and blood gene expression comparable to those observed in calves born to adequately fed dams. Full article

Multi-reference and density functional theory calculations are performed for the diatomic and ligated NpO³⁺ species. The main goal of this study is to provide insights into the stability of the experimentally synthesized N(CH₂CH₂NR)₃NpO (R = SiⁱPr₃) coordination complex and probe its use as a catalyst for the oxidation of methane. The constructed potential energy curves for NpO³⁺ showed the presence of three different types of minima (Np³⁺O, Np⁴⁺O⁻, Np⁵⁺O²⁻) depending on the neptunium–oxygen distance. All these minima are higher in energy than the Np²⁺ + O⁺ fragments, and the more stable Np⁵⁺O²⁻ form is stabilized only due to the presence of the negatively charged -CH₂NR⁻ moiety of the ligand. The C–H bond activation of methane was found to be possible only for the first quintet state of the complex which lies about 30 kcal/mol higher than the ground triplet state. Full article

Background: We previously pioneered a multigene mRNA test, qMIDS^V2, validated through an international multicohort study with geographically and ethnically diverse oral squamous cell carcinoma (OSCC) patients from Europe and Asia. This study aimed to repurpose the qMIDS^V2 test for nasopharyngeal carcinoma (NPC). A molecular test independent of Epstein–Barr virus (EBV) status would be clinically useful for risk stratification in NPC patients with undetectable or low levels of EBV. Methods: This study investigated a Chinese cohort of 62 participants (18 donated normal nasopharyngeal mucosa (NPM) and 44 donated NPC tissue samples). Messenger RNA levels of 16 genes in each sample were quantified using the qPCR method, and an algorithm computed a malignancy index for cancer risk stratification. Results: We identified a unique 10-gene panel (containing eight target genes, namely NEK2, INHBA, FOXM1, TOP2A, BIRC5, CXCL8, NR3C1, and IVL, relative to two reference genes, YAP1 and POLR2A, collectively named qMIDS^NPC) that demonstrated the best overall diagnostic performance in segregating NPM from NPC, with AUC = 0.909 and positive/negative predictive values of 91% PPV and 78% NPV, respectively. Furthermore, we demonstrated prognostic value of qMIDS^NPC in segregating NPM from NPC stage III + IV, with AUC = 0.936, 92% PPV, and 84% NPV. Conclusions: Here, we present a simple qPCR-based 10-gene mRNA test, qMIDS^NPC, with potential clinical utilities for rapid (1 h) prognostic stratification of NPC. Further studies involving geographically and ethnically independent NPC cohorts would be needed to validate the clinical use of qMIDS^NPC in non-endemic NPC populations. Full article

Background: We investigated whether a water extract of Lilii bulbus (Lilium lancifolium Thunberg; WELB) could modulate inhibitory synaptic organization in a mouse model of pentylenetetrazol (PTZ)-induced kindling. Methods: Starting 14 days prior to the initial PTZ challenge, WELB (500 mg/kg) was delivered via oral gavage once daily. This treatment regimen was maintained for a total of 40 days, spanning the entire period until the animals reached the fully kindled state. Results: Behavioral assessments revealed that WELB treatment significantly reduced seizure severity and Racine scores, prolonged the latency to clonic seizures, and shortened seizure duration, demonstrating potent anticonvulsant activity. Two-photon calcium imaging further showed that WELB markedly suppressed PTZ-induced neuronal hyperexcitability in the posterior parietal cortex, accompanied by decreased expression of neuronal activation markers, including c-fos, phosphorylated-calcium/calmodulin-dependent protein kinase IIα (p-CaMKIIα), and N-methyl-D-aspartate receptor 1 (NR1). In the hippocampus, WELB modulated the expression of GABAergic interneuron markers [glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT), parvalbumin (PV), somatostatin (SOM)] and upregulated GABAergic gene transcripts [GABA-A receptor α1 subunit (Gabra1), GABA-A receptor α2 subunit (Gabra2), GABA transporter 1 (Gat1), GABA transporter 3 (Gat3), PV, SOM, cholecystokinin (CCK)] that were downregulated by PTZ kindling. Moreover, WELB enhanced the expression of GABAergic synaptic organization-related proteins (gephyrin, collybistin, neurexin-1β, neuroligin-2, and neuropilin-2), indicating its regulatory effect on inhibitory synaptic integrity. Conclusions: Collectively, these findings suggest that WELB may exert its anticonvulsant effects by functionally remodeling GABAergic synaptic organization-related factors, thereby restoring inhibitory circuit integrity and providing a mechanism-based therapeutic strategy for epilepsy and seizure-related neurological disorders. Full article

The storage quality of fresh-cut peach fruit is compromised by weight loss and chromatic aberration. In this experiment, taurine at 30 mg L⁻¹ was applied to fresh-cut peaches to evaluate its effect on storage quality. Changes in weight loss, chromatic aberration, antioxidant system, endogenous nitric oxide (NO) metabolism, endogenous hydrogen sulfide (H₂S) metabolism, and phenylpropanoid metabolism were studied. The results indicated that 30 mg L⁻¹ taurine effectively improved the ability to scavenge ROS, including •OH, O₂^•−, MDA, and H₂O₂, by inhibiting the decrease in the activities of SOD and CAT, enhancing POD activity, reducing PPO activity, and maintaining the AsA-GSH cycle. Moreover, taurine treatment increased the activities of 4CL and PAL and retarded the decrease in the activities of SKDH and C4H, thereby improving the accumulation of total phenols, flavonoids, and lignin. These findings showed that taurine mitigated oxidative damage in fresh-cut peaches by enhancing the antioxidant defense system. Exogenous taurine consistently enhanced NOS-like activity while decreasing NR activity in the early storage phase, and elevated the contents of L-Arginine, nitrite, and endogenous NO. Taurine treatment up-regulated the activities of SAT, L-CD, and OAS-TL, thus promoting endogenous H₂S content in fresh-cut peaches. Taurine alleviated weight loss and chromatic aberration in fresh-cut peaches during storage by enhancing the antioxidant system and modulating NO, H₂S and phenylpropanoid metabolism. Full article

Background: Currently, the duration of tourniquet time in total knee arthroplasty is chosen by the surgeons and varies between 0 and 120 min. Studies evaluating the effect of tourniquet time in this surgery are heterogeneous, and there is limited information on molecular/complement profiling. The purpose of this study was, therefore, to determine whether the duration of tourniquet-induced limb ischemia during total knee arthroplasty influences reperfusion injury, resulting in pain, swelling, and the release of pro-inflammatory markers. Methods: In 40 patients undergoing total knee arthroplasty, a tourniquet was applied for up to 30 min (group A, short tourniquet) or 90–120 min (group B, long tourniquet). Postoperative pain and swelling served as primary outcome parameters. The levels of pro- and anti-inflammatory markers before surgery and 4 h, 24 h, and 48 h after surgery were used as secondary outcome parameters for exploratory testing. Results: There were no differences in numeric rating pain scale (NRS) scores and calf circumference between groups A and B. Patients in group B required patient-controlled intravenous analgesia more frequently than group A patients (47% versus 5%, group B vs. group A, p < 0.0001). In group B, a significantly higher increase in C3a and MIG levels between 4 h and 48 h, and a significantly higher increase for MIG and M-CSF between 24 h and 48 h, were observed. Conclusions: Tourniquet times between 90 and 120 min were not associated with higher pain levels or more swelling, but an increased need for intravenous analgesia and a higher increase in pro-inflammatory markers. This might be a consequence of a more pronounced ischemia/reperfusion injury with tourniquet times longer than 90 min. Full article

Fifth-generation (5G) mobile networks must simultaneously satisfy stringent latency targets, high user density, and energy-aware operation across heterogeneous services. Cloud Radio Access Networks (C-RAN) provide architectural flexibility through centralized baseband processing, but they also introduce new control challenges related to fronthaul constraints, dynamic traffic variations, and joint radio–compute coordination with Mobile Edge Computing (MEC). This paper proposes a unified AI-driven optimization framework for adaptive 5G C-RAN management, where the controller dynamically tunes key system decisions—including functional split selection, TDD downlink ratio, user–RU association, fronthaul load management, and MEC offloading proportion. To enable fair benchmarking under identical simulation settings, a static baseline policy is compared against five adaptive control strategies: Deep Q-Network (DQN), Proximal Policy Optimization (PPO), Deep Deterministic Policy Gradient (DDPG), Multi-Objective Reinforcement Learning (MORL), and a Deterministic Service-Level Agreement (SLA)-aware controller Penalty-Constrained Hierarchical Action Controller (PCHAC). Performance evaluation across techno-economic and service KPIs shows that intelligent control significantly improves operational profit, tail-latency behavior, and energy efficiency while enhancing SLA compliance compared with non-adaptive operation. The results highlight the practicality of multi-objective and constraint-aware learning for next-generation C-RAN orchestration under scaling traffic demand. Full article

Low-temperature stress adversely impairs rice germination and seedling establishment. This study assessed a nano-bio-priming strategy using lecithin (L) and silicon dioxide nanoparticles (SiO₂ NPs) to enhance chilling tolerance. Two fragrant rice cultivars (Xiangyaxiangzhan and Meixiangzhan 2) were primed with six combinations of lecithin (0, 50, and 100 μmol·L⁻¹, denoted as L0, L1, and L2) and SiO₂ NPs (0 and 100 mg·L⁻¹, denoted as S0 and S1) and exposed to optimal temperature (25 °C) or low-temperature stress (15 °C). Low-temperature stress delayed germination onset by two days. Combined priming treatments L1S1 and L2S1 significantly alleviated this inhibitory effect. Crucially, cultivar-specific responses were evident in Meixiangzhan 2, where L1S1 increased the germination vigor index by 50.97%. Meanwhile, the effect was less pronounced or inhibitory at normal temperature in Xiangyaxiangzhan. Priming substantially enhanced seedling growth, and L2S1 maximally increased root and shoot length in Meixiangzhan 2 by 55.30% and 15.82%, respectively. Furthermore, biomass accumulation was strongly promoted. L1S1 increased total dry weight and total fresh weight in Meixiangzhan 2 by 19.64% and 23.48%, respectively. Physiologically, priming elevated chlorophyll and carotenoid contents upregulated the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and increased levels of soluble protein and ascorbate (AsA), while maintaining nitrate reductase (NR) activity and hydrogen peroxide (H₂O₂) homeostasis. These physiological improvements were positively correlated with enhanced growth. Our findings demonstrate that co-priming with lecithin and SiO₂ NPs is a potent strategy for enhancing low-temperature tolerance, with efficacy depending on both the treatment combination and rice genotype. Full article