Cis-regulatory elements (CREs) drive tissue- and cell-specific gene expression and are essential for safe, sustainable genetic control strategies in pest and vector insects, including the engineering of gene drives in the primary human-malaria vector Anopheles gambiae. Yet CREs remain poorly defined in mosquitoes due to limited computational tools and practical methods for identification and validation. We present a systematic in silico approach for CRE discovery, correlating targeted DNA-motif searches with gene expression, followed by frequency and distribution analysis within putative promoter regions. Applied to the A. gambiae germline, this approach identified hundreds of putative CREs significantly correlated with germline expression in one or both sexes, often linked to distinct sperm developmental stages and chromosomal locations, suggesting roles in broader regulatory mechanisms such as dosage compensation and meiotic silencing. When mapped onto pre-characterised germline promoters, CRE distribution aligned with regions associated with experimental expression patterns. Finally, we validated a top-ranked testis-enriched CRE using an in vivo dual-reporter assay, showing that mutation of conserved nucleotides drastically altered male germline expression. To the best of our knowledge this work provides the first nucleotide-resolution regulatory genome annotation of the A. gambiae germline, offering a transferable framework to aid promoter design for genetic control strategies against malaria mosquitoes and other insect pests.
Visual impairment affects over 2.2 billion people worldwide and the major causes include age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. For research in these areas, although animal models offer a more physiologically complex system than in vitro approaches, their use raises ethical considerations, and species-specific differences such as variations in protein sequences and signaling pathways. This can limit the direct translatability of the outcomes. Traditional 2-D cell cultures, in contrast, lack the multicellular organization and dynamic microenvironment necessary to replicate human retinal complexity. Retinal organoids (ROs), three-dimensional tissue constructs derived from pluripotent stem cells, have emerged as a promising model due to their human origin and complex cellular interactions that cannot be achieved in conventional 2-D/3-D co-culture models. In this review, we provide a brief overview of the evolution from 2-D to 3-D retinal models, highlight the structural and functional features of ROs including the presence of layered retinal architecture, photoreceptor outer segment formation, and light-responsive electrophysiological activity and summarize their applications in disease modeling, drug discovery, and gene and cell therapy. ROs represent a significant advancement over traditional models by enabling the recapitulation of human-specific retinal development, facilitating the study of patient-derived disease phenotypes, and providing a platform for personalized therapeutic screening. Their development has deepened understanding of pathological mechanisms in conditions such as retinitis pigmentosa and AMD, while enabling preclinical testing of targeted interventions like CRISPR-based gene editing and photoreceptor cell replacement. Nonetheless, challenges remain in fully replicating retinal vascularization, long-term functional maturation, and synaptic connectivity, underscoring the need for continued refinement and integration with complementary model systems.
Human biomonitoring (HBM) is crucial for evaluating exposure to diet-related contaminants, whose effects may pose substantial health risks. Saliva is recognized as a promising non-invasive biological matrix due to its ease of collection and potential to reflect external and systemic exposure. However, suitability for monitoring dietary hazardous compounds remains uncertain. To assess the potential of saliva as a biomonitoring matrix for diet-related contaminants, identify compounds with robust diet-related associations, and highlight knowledge gaps. A systematic literature review was conducted to screen over 500 diet-related contaminants analyzed in saliva. Detailed information was extracted only for contaminants quantitatively measured in saliva, including concentration ranges, sample sizes, and analytical methods. Evidence of correlations with systemic concentrations, exposure pathways, and individual or lifestyle factors was compiled into a FAIR database to provide an integrated evaluation of saliva's biomonitoring potential. Only a limited subset of contaminant groups, including nitrite/nitrate, heavy metals, bisphenols, polycyclic aromatic hydrocarbons (PAHs), biogenic amines, pesticides, advanced glycation end products (AGEs), perchlorate, microplastics (MPs), parabens and phthalates, have been quantitatively measured in saliva. Compounds such as nitrate, arsenic, AGEs, pesticides and perchlorate demonstrate moderate to strong correlations between salivary and systemic levels, supporting saliva's potential to estimate exposure. Conversely, substances like PAHs, MPs, phthalates and parabens generally show weak or no correlation, reflecting recent or localised exposures rather than cumulative burden. Salivary composition is influenced by intrinsic and extrinsic factors, including diet, oral microbiota, physiology, and sampling conditions, resulting in high interindividual variability. Despite challenges, low salivary concentrations and lack of standardized collection protocols, saliva offers advantages for biomonitoring vulnerable populations, such as children and pregnant women. Harmonized collection procedures, validated sensitive methods, predictive models accounting for variability and exposure context, could establish saliva as a reliable complementary or alternative matrix for assessing human exposure to dietary and environmental contaminants. This systematic review synthesizes findings from 104 studies, covering over 500 diet-related contaminants measured in saliva, and compiles them into a FAIR database, providing the most comprehensive resource to date for saliva-based biomonitoring. Compounds such as nitrate, arsenic, advanced glycation end-products (AGEs), pesticides, and perchlorate show meaningful correlations with systemic levels, supporting saliva's potential as a non-invasive matrix for assessing human exposure. To fully realize saliva's potential, standardized collection protocols, validated analytical methods, and predictive models that account for interindividual variability and exposure context are urgently needed, enabling more accurate and ethical monitoring of vulnerable populations.
In this review we comprehensively discuss organic cation transporter novel 1 (OCTN1), encoded by the SLC22A4 gene as a member in the solute carrier 22 (SLC22) family, which facilitates the cellular transport of diverse cationic and zwitterionic substrates. OCTN1 is highly expressed in many vital organs in humans, where it facilitates absorption and distribution of both endogenous compounds and therapeutic drugs. Among its substrates, ergothioneine (EGT) serves as the primary antioxidant and anti-inflammatory molecule, underscoring the essential role of OCTN1 in cellular defense and inflammation control. Genetic polymorphisms in SLC22A4 significantly alter OCTN1 expression, substrate affinity, and drug pharmacokinetics, with strong associations to susceptibility and treatment outcomes in human diseases. Insights from knockout models revealed that OCTN1 deficiency leads to reduced EGT availability, heightened oxidative stress, and aggravated inflammation, particularly in the tissues such as intestine, liver and lung. Moreover, OCTN1 activity is dynamically regulated by epigenetic modifications, cytokines, and hormones, linking it to immune modulation and disease progression. Put together, OCTN1 plays a defined role via high-affinity EGT transport, while its broader transport capacity and pharmacological relevance remain under investigation, with possible - though not yet established - implications for inflammation-associated biomarker development.
Eukaryotic mRNAs typically encode a single functional polypeptide, a principle challenged by the discovery of widespread non-canonical peptide-coding ORFs within 5'UTRs. However, their functional significance at the protein level remains underexplored. Using a four-layered pipeline, we identify 14 human transcripts predominantly transcribed in polycistronic forms, each encoding two conserved proteins. Focusing on the SLC35A4 transcript, we show that its 5'UTR encodes a mitochondrial inner membrane-localized microprotein that we name STREMI (SLC35A4 stress response regulating MICOS interactor). Sharing topology and motifs with the MICOS core subunit MIC10, STREMI regulates mitochondrial cristae morphogenesis in mice and human cells. Additionally, the STREMI-encoding uORF mediates stress-responsive translation of SLC35A4-a Golgi nucleotide sugar transporter-upregulating its translation during the integrated stress response. Evolutionary analyses indicate that these bicistronic transcripts likely arose through transcriptional readthrough following retroposition. We propose a mechanism of "gene symbiosis" that enables functional partitioning and coordinated translation of protein pairs from bicistronic transcripts.
Cytokine-mediated cross-talk between immune cells and fibroblasts is a driver of excessive ECM accumulation during fibrosis. In this study, we used a 3D in vitro model of a connective tissue to discern the roles of three pro-inflammatory cytokines; TNF-α, IL-18 and IL-1β, alone, and in combination with TGF-β1 to simulate the fibrotic environment. Ring-shaped tissues were formed by seeding human fibroblasts into circular molds of agarose, wherein the cells self-assembled, formed a 3D tissue and synthesized de novo a collagen-rich ECM. Cytokine treated tissues were analyzed at days 7 and 14 by histology and measured for thickness, collagen, DNA and strength and stiffness by tensile testing. Despite their pro-inflammatory nature, none of the cytokines increased collagen alone or in combination with TGF-β1. TNF-α and IL-1β reduced collagen, tissue strength and stiffness, and altered tissue morphology. When combined with TGF-β1, TNF-α and IL-1β counteracted TGF-β1-mediated increases in collagen, strength, and stiffness. In contrast, IL-18 had minimal effects alone or when combined with TGF-β1. These data suggest that IL-18 has no effect on fibroblast activation, whereas TNF-α and IL-1β may modulate TGF-β1's effects. This 3D model of a human collagen-rich tissue can help define cytokine-mediated cross-talk between immune cells and fibroblasts.
Propofol is a widely employed intravenous general anesthetic that can induce neurotoxic effects on neurons. Previous research has indicated dysregulation of miR-140-3p in the hippocampal tissues of propofol-treated mice. This research was designed to investigate the function and underlying mechanism of miR-140-3p in propofol-induced neurotoxicity. To simulate propofol-induced neurotoxicity, human SH-SY5Y cells and mice were treated with propofol. Commercial kits were used to measure LDH, MDA, SOD, GSH-Px, and BDNF levels. Cells were transfected with miR-140-3p mimics, inhibitor, or BACE1 overexpression plasmids. Gene expression was assessed by RT-qPCR, cell viability by CCK-8, and apoptosis by flow cytometry. Dual-luciferase and RIP assays confirmed that miR-140-3p targets BACE1. The results confirmed that as the concentration of propofol increased, miR-140-3p levels were progressively downregulated, while BACE1 was correspondingly upregulated. Upregulation of miR-140-3p rescued propofol-treated SH-SY5Y cells from cytotoxicity, as evidenced by enhanced viability, suppressed apoptosis, and ameliorated oxidative stress. Consistently, miR-140-3p overexpression also attenuated propofol-induced neurotoxicity in vivo. Furthermore, BACE1 was confirmed to be a direct target of miR-140-3p through experimental validation, and this post-transcriptional repression was shown to mediate the observed neuroprotection. miR-140-3p attenuates propofol-induced neurotoxicity via BACE1 in vitro and in vivo, providing new insights and a potential biomarker for managing propofol-associated neurotoxicity.
To develop a semi-automated method to segment "black hole" lesions on post-gadolinium 2D T1-weighted images (GdT1) in multiple sclerosis (MS) that follows radiological intensity rules and perform multi-center validation. Multi-center spin-echo GdT1 images and accompanying proton-density (PD)/T2-weighted images and manual T2 lesion masks of the REFLEXION study (NCT00813709) of suspected/early MS were used. Briefly, the proposed method segments cortical gray matter (GM) to derive a T1-weighted intensity threshold, which is applied inside co-registered T2 lesion masks to segment black hole lesion voxels. It was optimized on a training set (N = 40, 57.5% female, mean age 31.4 ± 8.7 (standard deviation) years), and 274 patients formed the test set (61.3% female, age 31.8 ± 8.4 years). Performance was quantified by the Dice similarity coefficient (DSC) and the intraclass correlation coefficient (ICC) for absolute agreement with manual segmentations. Lesion-wise sensitivity and specificity were calculated. Optimization resulted in: (1) GM selection as minimally 0.8 total WM plus GM partial volume, masked by MNI cortex; (2) normalized mutual information-driven linear co-registration of T2 to GdT1 images, interpolating T2 lesion masks using trilinear interpolation and 0.6 threshold; (3) mean intensity inside GM mask used as upper intensity threshold. The optimized method had acceptable spatial accuracy (DSC: 0.39 ± 0.26) and good volumetric accuracy (ICC: 0.84, 95% CI [0.72, 0.90]. Lesion-wise sensitivity was 0.91 ± 0.19, and lesion-wise specificity was 0.62 ± 0.22. The proposed method to semi-automatically segment black holes from post-gadolinium T1-weighted images shows acceptable performance. As a potential aid to radiologists, the method is not recommended to be used entirely without human intervention. Question T1-hypointense "black hole" lesions reflect disease severity in multiple sclerosis but are not routinely quantified due to a lack of reliable analysis methods. Findings A rule-based semi-automated method for GdT1 "black hole" lesion segmentation was developed and optimized, and then validated in a large unseen multi-center test set. Clinical relevance This method adds quantitative information about GdT1 "black hole" lesions to the radiological assessment of multiple sclerosis disease severity, when false positives are manually removed. This can enhance the characterization of individual patients and advance the understanding of the disease.
Zoonotic diseases are common threats to global health. A large number of infectious diseases are transmitted from animals to humans. The current study aimed to assess the community's knowledge, attitudes, and practices (KAP) regarding common zoonotic diseases in the Arbaminch district. A cross-sectional survey was carried out between November 2024 and June 2025. A total of 384 participants were interviewed in the study. Participants residing in these areas were randomly chosen. Data were collected using a structured questionnaire. The collected data were analyzed using Stata 17, and the results were reported using descriptive statistics and the chi-square test. The findings of this study revealed that a majority (55%) of participants had good knowledge about zoonotic diseases. Respondents know several modes of transmission for zoonotic diseases, with animal bites (32.5%) being the most recognized, followed by direct contact (15.5%), ingestion of raw products (10%), and inhalation (10%). Regarding attitudes, 63.2% of respondents exhibited a positive attitude towards the importance of zoonotic disease prevention and control, and 67.4% of respondents followed relatively good hygiene and preventive behaviors. However, risky practices were still common. Knowledge score showed a significant association with age. Attitudes of participants were significantly associated with education, age, occupation, and income. Similarly, practices were significantly associated with gender, education level, occupation, and income, with all associations being statistically significant (p < 0.05). The overall community knowledge, attitudes, and practices regarding zoonotic diseases were relatively good.
The deltoid ligament (DL) is the primary stabilizer of the medial ankle, but its injury mechanisms remain poorly understood. This study aimed to investigate the injury risk and mechanisms of individual DL bundles under both acute and chronic conditions to inform prevention and treatment strategies. A validated finite element model of the human foot was used to examine peak stresses in DL bundles under four acute loading scenarios. Chronic loading was simulated by applying gait loads after transecting the lateral ligaments, and the resulting DL stresses were compared with those of the intact model. Additionally, thirty-nine rats were assigned to three groups: a lateral ligament rupture group (LR, n = 13), a tibialis posterior tendon rupture group (TPR, n = 13), and a sham group (n = 13). After 6 weeks of treadmill running, the mechanical properties and histological characteristics of the DL, along with ankle joint morphology and articular stresses, were evaluated to further verify the hypothesized mechanisms of chronic injury. Under acute loadings, the tibiocalcaneal ligament (TCL), anterior tibiotalar ligament (ATTL), and deep posterior tibiotalar ligament (dPTTL) showed the highest stress under pronation-external rotation loading. Lateral ligament rupture increased DL stress during gait. After 6 weeks of treadmill running, the LR and TPR groups showed roughened articular surfaces with osteophyte formation, increased articular stress, decreased talar bone volume fraction, lower failure load and stiffness ratios of the DL (p < 0.01), reduced fluorescence intensity of COL1, and elevated levels of COL3, MMP-2 and IL-1β compared with the sham group (p < 0.01). The TCL, ATTL, and dPTTL bundles are particularly susceptible to acute injury, with pronation-external rotation posing the greatest risk. Chronic degeneration of the DL occurs following rupture of the lateral ligament or tibialis posterior tendon, with a more pronounced effect after lateral ligament rupture.
The gut microbiome supports digestion, immunity, and metabolism; its imbalance (dysbiosis) drives inflammation and metabolic dysfunction, contributing to chronic diseases such as diabetes, cardiovascular disease, inflammatory bowel disease, and autoimmune disorders. Medicinal plants provide a wide range of phytochemicals (such as polyphenols, flavonoids, alkaloids, saponins), which reach the colon and undergo two-sided interactions with microbes in the gut, acting as potential microbiome modulators and substrates of biotransformation into bioactive metabolites. This structured narrative review synthesises evidence from peer-reviewed studies indexed in PubMed, Scopus, and Web of Science over the last 10 years on the role of medicinal plants in microbiome-mediated chronic disease modulation. This literature is organised into three mechanistic axes: (i) perturbations, defined here as measurable shifts in microbial diversity or taxonomic composition relative to a baseline or healthy reference state, together with beneficial taxa enrichment; (ii) alterations in microbial metabolite output, especially short-chain fatty acids (SCFAs) and other immunometabolic mediators; and (iii) downstream host metabolic and immune signalling. Rather than broad descriptive summaries, the literature is organised using an axis-based mechanistic framework, highlighting key translational constraints such as botanical heterogeneity, dose/formulation variability, and inconsistent microbiome endpoint standardisation, that must be addressed to strengthen human evidence and clinical relevance. Illustrative microbiome-mediated processes involve botanicals such as turmeric (curcumin), ginseng (ginsenosides), and green tea (catechins), though evidence strength varies by study design. Future progress requires standardised phytochemical characterisation, microbiome-stratified trials, and integration of multi-omics with artificial intelligence analytics to enhance mechanistic insight, identify responders, and enable personalised plant-based microbiome therapies.
Cold preservation is a critical logistical step in liver transplantation but induces ischemia-reperfusion injury (IRI), a key driver of early graft dysfunction. While bulk tissue assays capture global damage, they obscure the cell-type-specific transcriptional programs engaged during hypothermic storage. We utilized a multicellular human liver-on-chip model comprising Patient-Derived Organoids (PDOs), hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs), and macrophages. Chips were exposed to 24-h static cold storage using either the clinical standard University of Wisconsin (UW) solution or a hyperbranched polyglycerol (HPG)-based formulation, followed by normothermic reperfusion. Single-cell RNA sequencing (scRNA-seq) was performed to map transcriptional trajectories across the preservation-reperfusion axis. We identified candidate solution-dependent transcriptional differences across cell types. PDOs from UW-preserved chips showed comparatively higher mean expression of inflammatory and oxidative stress-associated transcripts (IFI27, SAA1, HMOX1) and mitochondrially-encoded genes (MT-ND5) relative to HPG-preserved samples, which retained comparatively higher expression of homeostatic epithelial markers (EPCAM, KRT18). HSCs and LSECs in the UW group showed comparatively elevated expression of fibrosis-associated (COL1A1, TAGLN) and endothelial adhesion (ICAM1) transcripts. Ligand-receptor interaction modelling identified candidate inflammatory communication axes, including chemokine signaling interactions (CXCL1, CCL20) between macrophages and epithelial compartments, with higher predicted activity under UW preservation. This study provides an exploratory, high-resolution map of cell-type-specific transcriptional patterns associated with hypothermic preservation in a liver-on-chip model. Our findings suggest that preservation solution chemistry is associated with distinct transcriptional signatures spanning stress response, mitochondrial, and intercellular signaling pathways. Transcriptional patterns in HPG-preserved cells were consistent with comparatively attenuated injury responses; however, these observations are hypothesis-generating and require independent biological replication and functional validation, including metabolic flux assays and ROS production measurements before conclusions regarding mitochondrial protection or clinical preservation efficacy can be drawn.
Chronobiology has advanced scientifically since 2000. Translating this knowledge and approach to medicine can alter diagnosis, treatment, and prevention, and improve health. Adding time-of-day (or time-of-year) information is both a concrete and conceptual change to clinical practice and public health relevant to humans and other animals, with low implementation costs. Successful translation of chronobiology to medicine requires new methods, training, and organizational and regulatory action.
Lung cancer is one of the most common malignancies and the leading cause of cancer-related mortality worldwide, posing a major public health challenge. Flavonoids, a large and diverse group of plant metabolites, exhibit various anticancer properties, making them promising candidates for therapeutic applications. This study evaluated the anticancer efficacy of methoxy flavonoids and elucidated their underlying mechanisms of action in A549 lung cancer cells. A549 cells were treated with various flavonoids (AKC1-AKC5), and their effects were analyzed using an MTT assay, DAPI staining, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, colony formation, and wound scratch tests. Molecular docking was also performed to confirm the binding of AKC1 and AKC3 to EGFR, BCL-2, and CDK-2 proteins. AKC1 and AKC3 prevented the growth of A549 lung cancer cells with IC50 of 64.57 and 19.80 μM among 5 methoxy flavonoids. AKC1 and AKC3 triggered notable alterations in the shape and reduced the colony-forming potential of A549 cells. The DAPI staining experiment demonstrated that AKC1 and AKC3 impede the growth of cancer cells through activation of apoptotic cell death. Moreover, the anticancer properties of AKC1 and AKC3 were attributed to significant inhibition of MMP and a notable ROS enhancement in a dose-related pattern. The wound scratch assay demonstrated that AKC1 and AKC3 suppressed A549 lung cancer cell migration, suggesting their anti-metastatic properties. Molecular docking studies confirmed that AKC-1 and AKC-3 bind strongly to EGFR, BCL-2, and CDK2, suggesting a multi-target mechanism that underlies their anti-proliferative and pro-apoptotic effects in A549 cells. AKC1 and AKC3 exhibited significant anticancer activity against A549 cells and may serve as promising therapeutic drugs for lung cancer treatment.
With the advent of the immunotherapy era, the combination of radiotherapy and immunotherapy has become a critical strategy to enhance patient outcomes. In addition to its direct cytotoxicity, radiotherapy modulates the immune response within the tumor and its surrounding microenvironment by stimulating the body's anti-tumor immune response. This interplay provides the rationale for combining radiotherapy with immunotherapy. This review will summarize the immunomodulatory mechanisms of radiation therapy, evaluate the clinical efficacy and safety of combining radiotherapy with immunotherapy, and outline its current applications, challenges, and future potential. In the future, the combination of radiotherapy and immunotherapy holds immense potential in esophageal cancer treatment. Through additional prospective clinical trials exploring optimal combinations, timing, and biomarkers, we can further refine treatment strategies and enhance patient survival.
To evaluate the feasibility and preliminary clinical outcomes of percutaneous endoscopic visual trephine decompression (PEVTD) in combination with pedicle screw fixation for the treatment of lumbar burst fractures with secondary spinal stenosis. A retrospective analysis was conducted on 21 patients with lumbar burst fractures and secondary spinal stenosis treated from December 2022 to December 2024. All patients underwent PEVTD combined with percutaneous pedicle screw internal fixation. The duration of endoscopic decompression surgery, blood loss, the incidence of intraoperative dural tearing, the Visual Analogue Scale (VAS) for pain score, the American Spinal Injury Association (ASIA) grade, and the MRI dural sac cross-sectional area were recorded to assess the effectiveness of decompression. The mean operative time for endoscopic decompression was 49.3 ± 10.2 min (41-60 min) with an estimated blood loss of approximately 160 ml. No intraoperative dural tearing occurred. Compared with the preoperative values, the postoperative VAS score and ASIA grade at 1 week and 1 year significantly improved(P < 0.05). The dural sac cross-sectional area increased significantly postoperatively (P < 0.01). PEVTD appears to be a feasible minimally invasive technique for treating lumbar burst fractures with secondary spinal canal stenosis in selected patients (those without posterior column injury and with ≤ 50% canal compromise). The preliminary results suggest that PEVTD is a feasible minimally invasive technique with short-term outcomes that appear acceptable in this selected cohort, although these findings are exploratory and require confirmation in prospective comparative studies.
BACKGROUND Kennedy disease, also known as spinal and bulbar muscular atrophy (SBMA), is a rare and incurable X-linked neuromuscular disorder mainly affecting men aged 30 to 60 years. Polymyositis can present similarly, but can be excluded by measuring muscle enzymes, performing muscle imaging, and electromyography. This report describes the case of a 52-year-old man with a 10-year history of progressive limb weakness due to Kennedy disease, established by genetic testing. CASE REPORT A 52-year-old man presented with a 10-year history of gradually progressive proximal limb weakness and persistently elevated creatine kinase levels ranging from 808-2300 U/L (normal 39-308 U/L). One year prior to this admission, the limb weakness had worsened, but initial electromyography, neuroimaging, and muscle biopsy showed no specific abnormalities. Despite a trial of immunosuppressive therapy due to suspected polymyositis, there was no clinical improvement. Neurological examination later revealed gynecomastia, proximal muscle atrophy, and bilateral tongue atrophy with tremor. Electromyography showed chronic neurogenic changes and reduced sensory nerve action potentials. Repeat expansion analysis identified a hemizygous pathogenic CAG repeat expansion in exon 1 of the androgen receptor gene using a short-read next-generation sequencing-based repeat detection algorithm (ExpansionHunter), with an estimated repeat number of 51 (range 50-53). At 6-month follow-up, the patient demonstrated mild progression of motor symptoms but remained functionally stable. CONCLUSIONS This report presents a rare case of Kennedy disease, initially diagnosed as polymyositis, and highlights the importance of follow-up with genetic testing when neurological and electromyography investigations are not typical for polymyositis. Early identification of Kennedy disease helps avoid unnecessary immunosuppressive treatments.
Residual cardiovascular risk persists despite intensive statin therapy in patients with established atherosclerotic cardiovascular disease (CVD). Omega-3 fatty acids, particularly high-dose eicosapentaenoic acid (EPA), have been proposed as adjunctive therapy, yet trial results conflict, likely due to formulation differences. We conducted a formulation-focused meta-analysis to determine whether high-dose EPA-dominant supplementation reduces cardiovascular events and to quantify the impact of mixed EPA/docosahexaenoic acid (DHA) regimens on efficacy. Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched MEDLINE, Embase, CENTRAL, and trial registries through May 2025 for randomized controlled trials, including placebo-controlled and open-label designs, of high-dose EPA-dominant omega-3 (≥ 1.8 g/day; ≥ 50% EPA) in adults with established CVD or other high-risk settings. Six trials (n = 42,738; 31-85% male) were eligible. Random-effects models generated pooled risk ratios (RRs), with I2 assessing heterogeneity; sensitivity analyses excluded mixed EPA/DHA formulations. Imaging surrogate outcomes were summarized narratively when study modalities were not directly comparable. EPA-based therapy significantly reduced hospitalizations for unstable angina (RR 0.75, 95% CI 0.66-0.87; I2 = 0%). Overall effects on recurrent myocardial infarction and revascularization were not statistically significant, but both became significant after exclusion of STRENGTH, the only mixed EPA/DHA cardiovascular outcomes trial. No significant effect was observed for ischemic stroke, cardiovascular death, or high-sensitivity C-reactive protein (hs-CRP). CHERRY and EVAPORATE both suggested attenuation of plaque progression, but these imaging studies were not pooled because intravascular ultrasound and coronary computed tomography angiography-derived measures were not directly comparable. High-dose EPA-dominant therapy was associated with fewer unstable angina hospitalizations, and formulation appeared to modify clinical benefit. Among blinded, placebo-controlled, cardiovascular outcomes trials, 4 g/day icosapent ethyl is the only formulation independently associated with reduced cardiovascular events. Larger formulation-specific trials are needed to clarify the roles of purified EPA, mixed EPA/DHA regimens, and patient selection. PROSPERO identifier number: CRD420251063069.
An accurate and precise analytical method was established for the determination of fenuron in carrot juice samples. Salt-assisted switchable solvent-liquid phase microextraction (SA-SS-LPME) was performed to achieve a lower detection limit. Three different calibration methods were compared to quadruple isotope dilution (ID4) in terms of accuracy and precision. Under the optimum SA-SS-LPME-GC-MS conditions, the linear range, coefficient of determination, limit of detection (LOD), and limit of quantitation (LOQ) were calculated as 0.12-2.85 mg/kg, 0.9988, 0.05 mg/kg and 0.15 mg/kg via the external standard calibration method, respectively. In addition, the internal calibration strategy was also implemented and the linear range, coefficient of determination, LOD and LOQ were found to be 0.12-5.13 mg/kg, 0.99996, 0.05 mg/kg and 0.17 mg/kg, respectively. Percent recovery results were recorded as 104.5%-118.1% (± 1.9-7.2) via the external standard calibration, 75.1%-115.0% (± 1.7-6.2) via the matrix-matching calibration, 89.7%-100.7% (± 1.8-6.3) via the internal standard calibration and 99.6%-102.0% (± 1.2-2.3) via the ID4 strategy. The recovery results obtained using the ID4 strategy demonstrate the advantage of integrating SA-SS-LPME-GC-MS with this approach.
Federated learning (FL) has become a highly promising paradigm for privacy-preserving distributed model training by enabling edge devices to train without sharing raw data. But in practice, edge environments are both non-stationary and asymmetric, with varying data distributions due to shifts in user behaviour, sensing conditions, and overall environmental dynamics. This causes concept drift (sudden, gradual, and recurrent), leading to poor model performance, slower convergence, and predictive bias. Current approaches to FL are not combined to tackle problems of drift adaptation, differential privacy (DP) and resource efficiency (FedAvg, DP-FedAvg). To address these constraints, we present FedDriftGuard. This Federated learning layer unifies client-level drift detection, drift-adaptive aggregation, and adaptable differential privacy into a single, FLE architecture-compatible system. The proposed DP-DriftNet model implements attention-based time encoding to capture changing data patterns and drift-directed feature weighting to allow greater flexibility in the presence of distributional changes. A drift-optimal privacy scheduler allocates noise probabilistically, subject to a limited privacy budget, thereby enforcing an appropriate privacy-utility trade-off without cancelling formal DP guarantees. Also, update sparsification, compression and periodic transmission techniques are used to reduce communication overhead. Decades of experimentation on real-world and synthetic drift datasets have shown that FedDriftGuard outperforms baseline FL techniques, achieving accuracy and F1-score gains of 9-14% and 11-17%, respectively, with adaptation latency 28% shorter and communication cost 20-35% lower. Such findings are statistically significant and confirm the soundness of the suggested method. FedDriftGuard offers effective, scalable privacy-preserving learning in adaptable, edge-drifting environments.