The aim of this study was to examine the modifying effect of body mass index (BMI) on the association of genome-wide association studies (GWAS)-significant for the level of sex hormones polymorphic loci with pre-eclampsia (PE). The work carried out genotyping of specially selected (according to data from previously conducted GWAS) 18 single nucleotide polymorphisms (SNP)that determine the content of various sex hormones in the organism. The sample of 891 pregnant women included two subgroups (they were formed based on the BMI values of women before pregnancy (pre-pregnancy BMI [preBMI]): preBMI < 25 (n = 592; 279 with PE/313 without PE) and preBMI ≥ 25 (n = 299; 152 with PE/147 without PE). The Firth’s penalized regression was used for the search of associations between SNPs and PE. As a whole, in the investigated cohort of women (PE [n = 431]/control group [n = 460], n = 891), an association of interactions of rs117585797 anoctamin-2 × preBMI with PE was found: ORA = 0.86, 95%CIA = 0.76–0.96, ppermt = 0.020. The results of our associative analysis in the two cohorts under consideration indicated the presence of a significant association only among women with preBMI < 25: SNP rs117585797 anoctamin-2 (C > A) was linked with PE risk (ORA = 2.69, 95%CIA = 1.26–5.72, ppermt = 0.011, power = 91.77%). In the women group with preBMI ≥ 25, we did not identify significant associations. The PE-associated locus rs117585797 of the anoctamin-2 gene and 14 of its LD variants were functionally significant for 57 proteins involved in PE-significant biological pathways such as regulation of gene expression, hormone- and estrogen-dependent processes, embryonic development, and adipogenesis. In conclusion, this study is the first to demonstrate a BMI—specific correlation between GWAS-significant for estradiol levels polymorphism rs117585797 anoctamin-2 (C > A) and PE: this SNP was PE-associated in preBMI < 25 pregnant women and not linked with PE risk in preBMI ≥ 25 pregnant women.
Background: Social interaction requires the efficient extraction and integration of visual information. Although atypicalities in global processing and visual perception have been reported in autism, their relationship with self-reported social-skills-related autistic traits remains unclear. Methods: Using an extreme-groups design, 179 university students completed the Autism-Spectrum Quotient (AQ). Individuals with scores at least ±1 SD were selected to form high-AQ (n = 20) and low-AQ (n = 22) groups. Participants completed two complementary psychophysical tasks assessing object perception under increasing visual noise and global–local visual processing. Results: The high-AQ group showed reduced recognition under high visual noise and slower responses under the global-incongruent condition. In the exploratory regression, visual-noise accuracy explained significant variance when entered alone, whereas global-incongruent Navon performance explained incremental variance and was the only significant unique contributor in the final model (R2 = 0.280). Conclusions: These findings suggest that, within the selected extreme-AQ sample, AQ Social Skills scores are associated with complementary visual mechanisms responsible for extracting relevant information from noisy environments and integrating spatially distributed visual information into coherent global representations. These behavioural findings are consistent with a possible link between visual processing and self-reported social traits and with theoretical models proposing a role for magnocellular-dependent dorsal visual computations in social perception, although these neural mechanisms were not directly assessed.
Population aging has intensified the search for natural compounds capable of promoting healthy aging and preventing age-related diseases. Among medicinal plants, species of the genus Crataegus (hawthorn) have attracted increasing attention because of their rich phytochemical composition and broad spectrum of biological activities. This review summarizes and critically evaluates current evidence on the geroprotective potential of Crataegus species, integrating data from phytochemical, pharmacological, and mechanistic studies. Particular attention is given to the major bioactive constituents of Crataegus, including flavonoids, oligomeric proanthocyanidins, phenolic acids, and triterpenoids, which exhibit antioxidant, anti-inflammatory, cardioprotective, neuroprotective, metabolic, and anticancer properties. We discuss the growing evidence that these phytochemicals target multiple hallmarks of aging by modulating oxidative stress, chronic low-grade inflammation (inflammaging), mitochondrial dysfunction, cellular senescence, and the senescence-associated secretory phenotype (SASP). Their biological effects are mediated through key signaling pathways involved in cellular homeostasis and longevity, including Nrf2/ARE, NF-κB, PI3K/Akt/mTOR, AMPK, and SIRT1. The review also critically examines findings from in vitro, in vivo, and available clinical studies, highlighting both the therapeutic potential and current limitations of Crataegus-based interventions for age-related disorders. Although preclinical evidence strongly supports the multi-target geroprotective properties of Crataegus species, clinical validation remains limited. Overall, Crataegus represents a promising source of natural geroprotective agents with the potential to promote healthy aging through the modulation of multiple aging-related molecular pathways. Future well-designed clinical studies are essential to establish their efficacy, safety, optimal dosage, and long-term therapeutic value in humans.
Hypertension is a major attributed cause of chronic kidney disease (CKD) and kidney failure, yet the cellular mechanisms linking chronic hemodynamic and neurohormonal stress to progressive nephron loss remain incompletely defined. Interpretation is further complicated by the clinical heterogeneity and limited pathological validation of hypertensive nephrosclerosis. Autophagy and mitophagy are important intracellular quality-control pathways and have been increasingly implicated in hypertensive kidney injury. In this review, we critically appraise the available evidence using a multidimensional ACGEM framework that evaluates autophagy/mitophagy measurement (A), cell-type resolution (C), genetic manipulation (G), experimental causality (E), and disease-model relevance (M) as independent dimensions. The available literature does not support a uniform increase or decrease in autophagy during hypertensive kidney disease. Rather, autophagic responses appear to depend on renal cell type, hypertensive stimulus, disease stage, and the component of the pathway being measured. In podocytes, chronic angiotensin II exposure provides evidence of impaired autophagic flux with a protective role for intact autophagy, whereas mineralocorticoid stress can induce a compensatory increase in autophagic flux. Tubular studies likewise suggest protective roles for effective autophagic and mitochondrial quality control, although direct cell-specific causal evidence in hypertensive models remains limited. Across the field, most studies rely on static autophagy-associated markers and bulk kidney measurements, while dynamic flux assessment, cell-specific genetic approaches, and direct evaluation of lysosomal competence remain uncommon. Observations from APOL1-associated kidney disease, chronic interstitial nephritis in agricultural communities, proteinuric overload, aging, and obesity provide mechanistic or pathological precedent for lysosomal vulnerability but do not constitute direct evidence for classical hypertensive nephrosclerosis. We therefore propose, as a falsifiable working hypothesis rather than an established mechanism, that lysosomal clearance may become rate limiting in a subset of hypertensive CKD. Testing this model will require longitudinal, cell-type-resolved flux measurements, direct assessment of lysosomal function, and pathological validation in biopsy-confirmed human hypertensive nephrosclerosis.
Aquaculture is a field that has developed rapidly over the past decade with the emergence of intensive farming systems that have significantly increased global fish production. However, this intensification has also led to the emergence of diseases caused by various pathogens, often resulting in extensive antibiotic use and, consequently, antimicrobial resistance (AMR). Consequently, research has focused on finding other sustainable alternatives to avoid the overuse of antibiotics and to protect both human and animal health. Probiotics and prebiotics have been extensively studied for their wide range of effects on growth, immunity, and the control of various pathogens. Through their complex mechanisms, they can also improve water quality, mitigate the effects of various physicochemical stressors, and enhance reproduction. This review aims to present the evolution of these concepts, with an emphasis on their effects, which often vary depending on the type of additive used, the dose, and the fish species.
Limestone karst habitats in tropical Asia support specialized and geographically restricted plant diversity, yet many areas remain incompletely explored. During botanical surveys of limestone habitats in northeastern Thailand, a distinctive, yellow-flowered population of Boesenbergia was discovered in Phu Pha Man District, Khon Kaen Province. Morphological observations were conducted on living plants in the natural population and spirit-preserved material, supplemented by comparisons with protologues, published descriptions, and herbarium material. Patterns of phenetic similarity among ten selected Boesenbergia taxa were evaluated using 32 morphological characters, Gower distance, UPGMA clustering, and principal coordinates analysis (PCoA). The population is described here as Boesenbergia calcicola Boonma, Saensouk & P.Saensouk, sp. nov. It is morphologically most comparable to B. petiolata but differs by its conspicuously exserted inflorescence, shorter bracts and flowers, distally puberulent floral tube, smaller puberulent lateral staminodes, and distinctive labellum color pattern. Phenetic analyses were used to summarize patterns of overall morphological similarity among the examined taxa. The species is currently known only from its limestone type locality at approximately 385 m a.s.l. and is provisionally assessed as Data Deficient (DD). This discovery further documents localized Boesenbergia diversity associated with limestone karst habitats in northeastern Thailand.
The Siberian sturgeon (Acipenser baerii, Brandt, 1869) is a potamodromous freshwater species with major ecological and commercial importance. Natural populations across the main Siberian River basins have declined so severely that the species is now classified as Critically Endangered on the IUCN Red List. This narrative analysis synthesizes current scientific knowledge regarding the ecology, reproductive biology, conservation status, and nutritional value of products derived from A. baerii, with the aim of providing an integrated perspective on this species, which has recently been introduced into Romanian aquaculture and occupies the interface between biodiversity and human consumption needs. The species’ remarkable ecological and morphological plasticity, which underlies its wide natural distribution in the Ob, Irtysh, Yenisei, and Lena River basins, has also made it the dominant species in global sturgeon aquaculture, commercially farmed in Europe, Asia, and South America. Reproductive management in farming systems relies on hormonal induction, non-invasive maturity assessment, and controlled hatchery practices, while emerging no-kill technologies enable repeated caviar harvesting without sacrificing the female, improving both ethical standards and economic efficiency. From a nutritional standpoint, A. baerii yields two high-value products: caviar, a rich source of the long-chain polyunsaturated fatty acids EPA and DHA, whose dietary intake has been associated with cardiovascular and neurodevelopmental benefits in the broader nutrition literature, and meat, characterized by high-biological-value protein, a favorable amino acid profile, and significant omega-3 content. By-products such as skin, swim bladders, glands, and cartilage contribute to the higher-value utilization of the species within the circular bioeconomy. Still, notable gaps remain in genetics and sex determination methods, in early life behavioral ecology, and in cryopreservation protocols. Future work should also look at more sustainable feed formulations and new value-added products.
Background: Lipedema is a chronic progressive condition affecting approximately 10% of women, characterized by disproportionate subcutaneous adipose tissue accumulation and pain in the lower extremities. Standardized assessment methods for pain evaluation in lipedema remain limited. The Progressive Pain Check (PPC) method represents a potentially valuable tool for standardized pain assessment in lipedema patients. Objective: To evaluate the inter-rater reliability of the PPC method for clinical assessment of evoked pain in lipedema patients. Methods: Two independent assessors performed PPC evaluations. Inter-rater reliability was assessed using the Intraclass Correlation Coefficient [ICC(2,1), two-way random-effects, absolute agreement, single-measurement] with 95% confidence intervals (CI). Results: This study included 429 women diagnosed with lipedema (mean age 41.2 ± 11.5 years, mean disease duration 27.2 ± 12.6 years). Patient characteristics revealed mean BMI of 29.5 ± 6.9 kg/m2, predominantly Type III lipedema presentation, and disease onset during adolescence (mean age 14 ± 9.3 years). The PPC method demonstrated excellent inter-rater reliability between two independent assessors across all examined anatomical districts. Conclusions: The PPC method shows promise as a simple, repeatable, and standardized clinical tool for evoked pain assessment in lipedema patients. The demonstrated inter-rater reliability supports its potential utility in clinical practice. Further research is warranted to evaluate its intra-rater reliability, concurrent validity, and responsiveness in monitoring treatment effects.
Long-term crewed space missions will have significant constraints on the weight and volume of supplies. The food needed and the management of the waste produced present a challenge, demanding technologies that effectively recycle nutrients. Using microbiological processes may be a way to meet this challenge. Here, we suggest that byproducts of anaerobic wastewater digestion (organic acids, H2, and CO2) could be paired with waste CO from atmospheric regeneration to produce microbial biomass, specifically Acetobacterium woodii and Rubrivivax gelatinosus, as a food source. First, we showed that the thermodynamics of key reactions are favorable. Next, we conducted nutritional analyses to evaluate suitability of A. woodii and R. gelatinosus as potential food supplements. A. woodii biomass consisted of 21% protein and 11% lipid on a dry mass basis. R. gelatinosus biomass consisted of 54% protein and 21% lipid on a dry mass basis. Finally, we conducted growth experiments for R. gelatinosus under varied (ammonium) acetate concentrations. Following the observation that an intermediate amount of acetate produced the most biomass, a second growth experiment showed that a high level of acetate, rather than ammonium, wasthe observed inhibiting factor. This perspective hopefully inspires new research establishing systems where waste products are recycled via microbial growth during long-term space flight.
Nursery habitats sustain fish populations by supporting early life stages and buffering environmental variability, yet their functioning under climate oscillations remains poorly understood in the Eastern Tropical Pacific. We analyzed ichthyoplankton assemblages in the Gulf of Tortugas, Colombia (2010–2020), to assess taxonomic composition, spatiotemporal variability, and environmental drivers. ENSO cycles and local oceanographic conditions were evaluated as determinants of nursery function and resilience using richness estimators, diversity indices, Caswell’s neutral model, and multivariate approaches (PERMANOVA, PERMDISP, CAP, BIOENV). Assemblages were dominated by Cetengraulis mysticetus, with recurrent contributions from Sciaenidae, Haemulidae, Gerreidae, and Carangidae—families of artisanal fisheries importance. ENSO phases explained interannual variability: El Niño years reduced diversity and weakened retention, whereas La Niña years supported more balanced assemblages. Spatial heterogeneity revealed central retention zones and peripheral diversity hotspots. Environmental gradients, particularly chlorophyll-a, zooplankton biomass, transparency, and pH, consistently structured larval distribution, reflecting the coupling of productivity, water quality, and circulation. These findings demonstrate that the Gulf of Tortugas functions as a dual nursery system and ecological node of resilience, underscoring the importance of protecting such habitats for ecosystem-based fisheries management and biodiversity conservation in a changing ocean.
Cancer immunotherapy faces significant challenges in treating “cold” tumors, which respond poorly to current strategies. Breast cancer is a major cause of cancer-related mortality in women and is a representative immunosuppressive cold tumor. The luminal A subtype of breast cancer exhibits an immune-cold phenotype, with MCF-7 cells used as a representative cell model. Here, we identified (3β,5α,8α)-5,8-epidioxyergost-6-en-3β-ol (EEO), isolated from Gymnopilus orientispectabilis, as an inducer of immunogenic cell death (ICD) hallmarks in MCF-7 cells, including cell surface exposure of calreticulin (CRT) and the extracellular release of damage-associated molecular patterns (DAMPs), such as ATP and High Mobility Group Box 1 (HMGB1). These ICD-associated events subsequently promoted CRT-dependent dendritic cell (DC) activation in a co-culture system with bone marrow-derived DCs and MCF-7 cells. Furthermore, surface-exposed CRT enhanced the phagocytosis of EEO-treated MCF-7 cells by DCs, and this phagocytic activity promoted DC maturation, as indicated by increased cell surface levels of the maturation markers major histocompatibility complex class II (MHC II) and cluster of differentiation 86 (CD86). Moreover, CRT knockdown in MCF-7 cells reduced surface CRT exposure following EEO treatment, thereby suppressing DC-mediated phagocytosis and subsequent DC maturation. Taken together, these findings suggest that EEO is a promising candidate for enhancing the antitumor efficacy of existing breast cancer immunotherapies through ICD-mediated DC maturation and converting immunologically cold tumors into hot tumors.
Despite the high global prevalence of depressive and anxiety disorders, access to early clinical assessment remains limited for many. Although this field has grown rapidly, existing reviews have focused primarily on technical performance, with limited systematic attention to whether current models meet the prerequisites for clinical implementation. This scoping review mapped methodological approaches across this domain and evaluated clinical readiness using five predefined indicators: sample size adequacy, external validation, prospective data collection, real-world evaluation, and model explainability. Searches of PubMed, Web of Science, and IEEE Xplore (March 2026) identified 2463 records; 34 studies (37 dataset evaluations) were included. The majority of studies (91%) were published from 2022 onwards. Depression was the primary target in 91% of studies, while only one study addressed anxiety. Hand-crafted acoustic features were the most frequent (57%), while classical machine learning was the most common model type (32%). External validation was conducted in only 32% of evaluations and real-world testing in 8%. Clinical readiness was classified as Low in 24%, Moderate in 65%, and High in 11% of evaluations. No evaluation met all five indicators simultaneously. These findings apply primarily to voice-based depression screening; 36 of 37 evaluations targeted depression, and the evidence base for anxiety disorders is limited to a single evaluation, precluding comparable characterisation for that condition. The principal challenges to clinical implementation are insufficient external validation, reliance on laboratory conditions, narrow linguistic coverage, and inconsistent metric reporting. The framework applied in this scoping review provides a replicable structure for assessing the clinical validity of AI-driven psychiatric screening tools.
Background: Lateral elbow tendinopathy (LET) is a common upper-limb musculoskeletal disorder causing pain during gripping activities, reduced work capacity, and functional limitation. LET is currently considered a predominantly degenerative condition characterized by collagen disorganization, extracellular matrix changes, neovascularization, and impaired tendon healing. Objective: To evaluate short-term clinical and functional outcomes of a multimodal protocol including focused extracorporeal shock wave therapy (f-ESWT), ultrasound-guided intralesional injection of low-molecular-weight peptides (LWPs) derived from hydrolyzed bovine collagen and therapeutic exercise in patients with chronic LET unresponsive to standardized conservative therapy. Methods: This retrospective observational study included 11 screened patients; 10 completed follow-up. Eligibility required age ≥ 18 years, symptoms ≥ 3 months, positive provocation tests, ultrasound-confirmed common extensor tendon pathology, and incomplete response to prior treatment. All patients received f-ESWT before ultrasound-guided LWPs injection and performed progressive loading exercises. Outcomes included Patient-Rated Tennis Elbow Evaluation (PRTEE), grip strength, and clinical provocation tests at baseline (T0; Day 0) and at T1 (Day 51, 30 days after injection). Results: PRTEE pain improved by 31.2 points (95% CI 22.2–40.2; Cohen’s d_z = 2.48) and PRTEE function by 32.6 points (95% CI 26.7–38.5; d_z = 3.95). Mean maximal strength and maximal strength improved by 4.61 kg (95% CI 2.89–6.32) and 4.02 kg (95% CI 2.36–5.68), respectively. Clinical test severity decreased by an estimated 2.5 points (95% CI 2.0–3.0). No adverse events were reported. Conclusions: Patients showed clinically meaningful short-term improvements in pain, function, and strength following the sequential multimodal management strategy. However, the retrospective design, small sample, lack of control group, and short follow-up preclude causal attribution and require confirmation in prospective controlled studies.
(1) Background: Adipocyte differentiation involves coordinated changes in mitochondrial activity, redox balance, and cellular metabolism. Here, we examined how quercetin affects lipid accumulation and associated mitochondrial-redox and metabolic features during 3T3-L1 adipogenic differentiation by combining functional assays with time-resolved 1H NMR metabolomics. (2) Materials and methods: 3T3-L1 cells were differentiated for six days in the absence or presence of 20 μM quercetin. Lipid accumulation, mitochondrial membrane potential, intracellular reactive oxygen species (ROS), and intracellular metabolite profiles were assessed at defined stages of differentiation. (3) Results: Quercetin reduced lipid accumulation, mitochondrial membrane potential, and ROS accumulation, particularly at the mid-to-late stages of adipogenic differentiation. 1H NMR analysis showed lower lipid-associated resonances and changes in metabolites related to energy metabolism, choline metabolism, and amino acid metabolism in quercetin-treated cells. Orthogonal partial least squares-discriminant analysis (OPLS-DA) showed separation of the metabolic profiles of untreated and quercetin-treated cells at each measured stage. The variables contributing to this separation included lipid-associated resonances, lactate, 3-hydroxybutyrate, choline-related metabolites, and selected amino acids. (4) Conclusions: The results indicate that quercetin reduces lipid accumulation during adipogenic differentiation in association with changes in mitochondrial-redox status and intracellular metabolic profiles. Overall, the findings support stage-dependent alterations of metabolic profiles in quercetin-treated 3T3-L1 cells during adipogenic differentiation.
Extreme ultramarathon running provides a unique human model for examining physiological responses under sustained metabolic stress. This study compared acute endocrine and lipid responses across 100, 308, and 622 km ultramarathon events, with particular attention to whether these responses were uniformly amplified with increasing race distance or differed according to event characteristics. Forty-four experienced male ultramarathon runners participated in the study (100 km group: n = 17; 308 km group: n = 18; 622 km group: n = 9). Venous blood samples were collected within 2 h before race start and generally within 5 min after race completion, and post-race biochemical concentrations were corrected for participant-specific plasma volume changes. Insulin and triglycerides decreased significantly across all three events, whereas T3 and HDL-C increased across all events. FSH and C-peptide decreased significantly in the 100 and 308 km groups, and FT4 increased significantly in these two groups. LH showed a significant time × event group interaction, with a significant reduction in the 100 km group and no significant within-group change in the 308 or 622 km groups. Because LH secretion is pulsatile and only one venous sample was obtained at each pre- and post-race time point, these findings should be interpreted as acute differences in circulating LH concentrations rather than evidence of altered gonadotropin regulation or hypothalamic–pituitary–gonadal axis suppression. Total cholesterol decreased significantly only after the 622 km event, whereas LDL-C decreased after the 308 and 622 km events. The observed endocrine and lipid response patterns differed across ultramarathon events characterized by distinct cumulative durations, pacing characteristics, nutritional exposure, hydration conditions, and recovery opportunities. Extreme ultramarathon running may therefore serve as a useful physiological model for investigating context-dependent endocrine and lipid responses to prolonged endurance stress.
Earth’s early history provides the only natural record for evaluating how planetary evolution can generate environments capable of initiating life. Here we review early Earth evolution through the lens of urability: the time-dependent capacity of planetary environments to support prebiotic chemistry progressing toward compartmentalized, self-propagating, information-bearing systems. We argue that urability is not a single globally habitable state, but a transient overlap among several coupled dimensions: liquid water availability, permissive temperature, ocean pH and salinity, access to bioessential elements, atmospheric shielding and volatile retention, and exposed or shallow environments that enable concentration, mineral catalysis, and wet–dry cycling. During the Hadean–early Archean transition, these dimensions were shaped by magma-ocean degassing, late accretion history, atmospheric compositional evolution from CO2-rich to more N2-dominated states, ferruginous ocean chemistry, tectonic recycling, continental growth, and intermittent land emergence. These processes created tradeoffs: high pCO2 may have enhanced abiotic nitrogen fixation but imposed hot and acidic conditions, whereas CO2 drawdown improved climate and ocean pH while weakening some fixed-nitrogen sources; ferruginous chemistry could locally enhance phosphate availability while also promoting nutrient scavenging; and tectonic recycling could stabilize the carbon cycle while generating chemically diverse but spatially intermittent land environments. We therefore frame life’s origin as a planetary timing problem, in which prebiotic opportunities opened and closed as multiple environmental constraints came into and out of overlap. This perspective motivates coupled models that resolve when and where water, temperature, pH, nutrients, energy, atmospheric photochemistry, and exposed land surfaces jointly produced urable environments on Earth and other rocky planets.
Altered red blood cell (RBC) deformability can impact microvascular flow resistance through changes in cell partitioning at bifurcations, and local hematocrit distribution, a key determinant of the effective viscosity of blood. In this work we report on resistance-relevant viscosity distributions extracted from in vitro microfluidic observations of a Y-junction type blood flow. Spatially resolved hematocrit distributions in the parent channel and daughter branches, determined by experimental measurements in earlier work, for healthy and stiffened RBC suspensions over a range of daughter to parent flow-split ratios, Q*, are combined with a recently proposed viscosity model enabling the estimation of the local relative viscosity profiles ηr. The maximum of the RBC elongation index EI, was utilized to define of the deformability parameter λ, which with the local RBC volume fraction, Φ(y), were used as inputs in the relative viscosity, ηr. The latter is a modified Krieger–Dougherty viscosity expression, accounting explicitly for deformability and RBC concentration. The resulting viscosity profiles are averaged in the channel regions of interest to provide an apparent viscosity in the branches, used here as an indicator of microvascular flow resistance. The results illustrate that deformability and hematocrit-dependent RBC enrichment or depletion in the branches of a vascular junction may amplify or attenuate the resistance asymmetry in the daughters of the Y-junction.
Objective: Patients with systemic lupus erythematosus (SLE) exhibit elevated malignancy risk, with increased bladder cancer incidence. This study integrated Mendelian randomization (MR) with single-cell sequencing (scRNA-seq) to nominate exploratory prioritized candidate genes in SLE–bladder cancer comorbidity and their T cell regulatory roles. Methods: Single-cell datasets for SLE (GSE266852) and bladder cancer (GSE222315) were retrieved from GEO. Quality control, clustering, and annotation were performed using Seurat. T cell differentially expressed genes were intersected for bidirectional two-sample MR using IEU Open GWAS statistics. Heterogeneity, pleiotropy, and sensitivity analyses assessed robustness. GeneMANIA, miRNA databases, and CTD were used for network and functional analyses. Wilcoxon tests and Monocle 2 were used to characterize expression and T cell differentiation trajectories. Results: Cross-disease intersection nominated 1010 candidate genes. In an exploratory MR screen (uncorrected p < 0.05), four candidate genes were nominated (GBP3, LMAN1, SLC40A1, MIS18BP1); none survived FDR correction in both directions. At the uncorrected threshold, LMAN1 showed a shared risk direction (OR > 1) and MIS18BP1 a protective direction (OR < 1). Both showed significant T cell differential expression (p < 0.001) and elevated late differentiation expression. LMAN1 was involved in COPII vesicle transport; MIS18BP1 in CENP-A chromatin assembly. Twenty high-confidence miRNAs targeted each gene. CTD indicated liver injury associations and cisplatin/cyclosporine interactions. Conclusions: LMAN1 and MIS18BP1 are proposed as hypothesis-generating exploratory candidate genes in SLE–bladder cancer comorbidity, potentially involved in immune dysregulation through T cell terminal differentiation modulation. This study provides preliminary evidence suggestive of autoimmune–malignancy comorbidity mechanisms.
Atrial fibrillation (AF) is traditionally classified using categorical clinical patterns and binary recurrence endpoints. However, these measures do not fully reflect arrhythmia frequency, duration, temporal distribution, or progression. AF burden, defined as the proportion of monitored time spent in AF, provides a more granular measure of disease activity and therapeutic response. Recent advances in cardiac implantable electronic devices, insertable cardiac monitors, wearable technologies, and digital platforms have significantly improved burden assessment, although considerable heterogeneity remains in monitoring methods, definitions, and clinically relevant thresholds. This review examines contemporary approaches to AF burden measurement and its associations with thromboembolic risk, heart failure, hospitalization, symptoms, quality of life, disease progression, and mortality. We particularly discuss the reduction of AF burden as a potential therapeutic target following antiarrhythmic drug therapy and catheter ablation, and the limitations of conventional recurrence definitions based on episodes lasting more than 30 s. This review also focuses on the implications for rhythm-control selection, post-ablation monitoring, anticoagulation, and clinical-trial design, while proposing priorities for standardized burden-based assessment.
This study focused on dietary supplementation with flaxseed in fattening pigs to observe health benefits and important biological findings, including cell membrane integrity, proliferation, and angiogenesis. Animals received flaxseed for 6 or 3 weeks prior to slaughter. Pigs were divided into a control group (standard diet) and experimental groups F6 (6 weeks) and F3 (3 weeks), which received flaxseed in the feed. Spectroscopy followed by an electrophoretic method was used to study the levels of basic biochemical parameters, including LDH. Subsequently, gas chromatography revealed fatty acid concentrations in the pigs’ livers, and finally, immunohistochemical analysis was used to detect CD31 and PCNA antigens in the liver and jejunum. The highest weight gain was measured in the F6 group. After slaughter, blood samples revealed a decreased glucose level in the F6 group, maintained levels of basic biochemical parameters, and decreased concentrations of LDH in blood, heart, liver, and skeletal muscle extracts, thus improving cell membrane integrity. A long-term supplementation period led to better utilization of essential fatty acids, an improved n-6:n-3 ratio, and other atherogenic indices related to cardiovascular health. Flaxseed also affected the expression of CD31 and PCNA proteins in the liver and jejunum, mainly in the F6 group.
