Search Results (206)

Background: Acrylamide (ACR), a toxic compound formed during high-temperature cooking of carbohydrate-rich foods, is known to induce multi-organ toxicity, including oxidative and inflammatory lung injury. N-Acetylcysteine (NAC), a precursor of glutathione (GSH), possesses potent antioxidant and anti-inflammatory properties that may counteract ACR-induced pulmonary damage. This study investigated the protective effects of NAC against ACR-mediated lung toxicity, with an emphasis on the GSK-3β/Nrf2/NF-κB signaling axis. Methods: Forty male Wistar rats were allocated into four groups: control, NAC (250 mg/kg/day), ACR (50 mg/kg/day), and NAC + ACR. After 11 days of treatment, lung tissues were examined histopathologically using H&E, PAS, and Masson’s trichrome stains. Oxidative stress biomarkers (MDA, SOD, GPx, CAT, GSH) were quantified biochemically. Immunohistochemistry and qRT PCR assessed expression of Nrf2, NF-κB, IL-1β, and Caspase 3, while ELISA measured TNF α, IL-6, Bax, Bcl 2, and GSK 3β. Results: ACR exposure resulted in severe lung injury characterized by alveolar wall edema, epithelial hyperplasia, leukocytic infiltration, goblet cell hyperplasia, and peribronchiolar collagen deposition. These pathological changes were accompanied by a marked increase in MDA, NF-κB, IL-1β, TNF α, IL-6, Bax, Caspase 3, and GSK 3β, together with significant reductions in antioxidant enzymes and Nrf2/HO 1/NQO1 expression. NAC co-administration significantly ameliorated ACR-induced lung damage, restoring normal histological architecture, reducing fibrosis, and normalizing goblet cell activity. NAC also reversed oxidative stress, enhanced Nrf2 and downstream antioxidant responses, suppressed NF-κB-mediated inflammation, and mitigated apoptosis. Notably, NAC downregulated ACR-induced GSK 3β activation, thereby contributing to balanced redox and inflammatory signaling. Conclusions: NAC confers significant protection against ACR-induced pulmonary toxicity through its antioxidant, anti-inflammatory, and anti-apoptotic activities. These effects are mediated, at least in part, by modulation of the GSK 3β/Nrf2/NF-κB pathway. NAC demonstrates promising therapeutic potential for preventing chemically induced lung injury. Full article

Biologic and targeted synthetic therapies have substantially improved the management of autoimmune diseases (ADs), achieving unprecedented disease control. However, by modulating key immune pathways, these agents increase susceptibility to a wide spectrum of infections. This narrative review synthesizes current evidence on infectious risks associated with biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) in AD, characterizing infection profiles across different drug classes, identifying patient- and treatment-related risk factors, and providing evidence-based recommendations for screening, prevention, and management. A comprehensive literature search was conducted through March 2026, across PubMed, Embase, and the Cochrane Library, using predefined search terms combining biologic and targeted synthetic drug classes with infection-related outcomes. Evidence from major international registries (BSRBR-RA, DANBIO, RABBIT) and society guidelines (ACR, EULAR, IDSA) was prioritized. Among bDMARDs, TNF-α inhibitors (TNF-α i) and rituximab were associated with the highest rates of serious infections, whereas IL-17 and IL-23 inhibitors demonstrated comparatively lower infectious risk profiles. Steroids, older age, and prior serious infections emerged as the most consistent patient-related risk modifiers. Unlike prior reviews focused on single diseases or drug classes, this work provides an integrated, cross-disciplinary risk stratification framework. bDMARDs and tsDMARDs remain among the most innovative treatments available for effective management of ADs, with favorable benefit–risk profiles when accompanied by systematic prevention strategies. Universal pre-treatment screening for tuberculosis and viral hepatitis, risk-stratified parasitic screening, evidence-based vaccination, and selective antimicrobial prophylaxis can mitigate infectious complications. Full article

Numerical simulations quantify the transient impacts of implementing green infrastructure (GI) grass swales on unconfined aquifer storage and groundwater-surface water interactions around the Red Butte Creek (RBC) of Utah, USA. The Red Butte Creek Watershed (RBCW) transitions from undeveloped mountainous National Forest land to downstream urbanized areas within Salt Lake Valley (SLV). This reconnaissance-level study demonstrates that increasing stormwater infiltration in urbanized areas during the rainy months (April-June) can, until at least the subsequent March, (a) enhance aquifer recharge and support sustainable groundwater yields; and (b) improve surface water availability. Simulations predict hydrologic impacts of aquifer recharge resulting from hypothetical grass-swale implementation within a 704-acre area located around RBC. The employed model, HyperRBC, is an adaptation of a United States Geological Survey (USGS) transient numerical flow, MODFLOW, model implementation for SLV. Adaptations involved (a) uniformly refined horizontal discretization of seven aquifer layers within a sub-area encompassing parts of RBCW and an adjacent watershed; (b) updated input data; and (c) MODFLOW’s Streamflow-Routing (SFR) package to simulate RBC flow and aquifer-stream seepage. Model predictions indicated that by the end of next March: (a) about 3% of the GI-induced recharge would remain within the unconfined aquifer in the HyperRBC area; (b) 66.6% of the recharge would flow northward into the downgradient continuation of the unconfined aquifer; and (c) 30.3% would discharge to nearby stream and river. In summary, predicted hydrologic changes due to the short-term GI-induced recharge highlight increased groundwater availability within and outside the study area for at least the subsequent 12 months, including high-water-demand summer. These findings show the importance of GI in interim environmental management and in enhancing the effective use of water resources. Full article

Aflatoxin B1 (AFB1) induces hepatocellular damage through its metabolite aflatoxin B1-8,9-epoxide (AFBO), which is produced in endoplasmic reticulum (ER) via cytochrome P450 (CYP450) enzymes. To investigate the effect of ferulic acid (FA) on AFB1-induced broiler liver damage, one-day-old Arbor Acres broilers were exposed to AFB1 (4 mg/kg) and treated with different doses of FA (60 mg/kg, 120 mg/kg, and 240 mg/kg) continuously for 28 days. The production performance, biochemical indicators, morphological changes, CYP450 enzymes’ expression in ER, interactions between small molecules and CYP450 enzymes, and CYP450 enzymes’ protein secondary structure were investigated. The results showed the following: (I) FA promoted broiler growth and reduced AFBO production. (II) AFB1-induced changes in serological indicators (AST, ALT, ALP, γ-GT, TBA, TG) and biochemical parameters (GST, SOD, MDA, ROS), which were reversed by FA. (III) AFB1-induced liver morphological changes and apoptosis were obviously alleviated by FA. (IV) AFB1-induced up-regulation of CYP1A5, CYP2A6, CYP2W1, and CYP3A4 in ER were reduced by FA. (V) The binding affinity of FA to CYP1A5 is lower than that of AFB1 to CYP1A5, and the binding affinity of FA to CYP2W1 is similar to that of AFB1 to CYP2W1. (VI) The contents of α helix, β sheet, β turn, and random coil in chicken CYP1A5 were 59.6%, 7.8%, 13.6%, and 19.0% respectively, and those in chicken CYP2W1 were 32.2%, 17.1%, 16.8%, and 33.9% respectively. In conclusion, FA can promote broiler growth and alleviate AFB1-induced hepatotoxicity via inhibiting and conjugating CYP450 enzymes, thus reducing AFBO formation and oxidative damage. Full article

X-ray crystallography is still the most widely used and versatile method for structural studies of biological macromolecules. This study concerns the application of nanogels to facilitate protein crystallization, a prerequisite for X-ray crystallography. Nanogels (NGs) are nano-sized, highly crosslinked polymeric particles that have been extensively studied for chemical catalysis and drug delivery but not for protein crystal nucleation. The efficacy of six types of nanogels (three N-isopropylacrylamide-based and three acrylamide-based) was tested, with promising results. They were subsequently functionalised with active hydroxyl groups for further testing. Both functionalised and non-functionalised nanogels were tested on model (trypsin, thaumatin, proteinase K, ferritin and catalase) and target proteins (glulisine, α-crustacyanin and acriflavine resistance protein subunit AcrB) using both manual and automated techniques. All nanogels were found to be effective in promoting protein crystallization in both screening and optimization trials, giving crystal ‘hits’ that would have otherwise been missed. Overall, the functionalised nanogels were more effective. Nanogel effects are proposed to be due to a combination of surface porosity and surface chemistry. Full article

Background: Sjögren’s disease (SjD) is a chronic autoimmune rheumatic disorder primarily affecting exocrine glands, leading to dryness and systemic involvement. B-cell hyperactivity and autoantibody production drive its pathogenesis and contribute to increased lymphoma risk. Although several long-term studies exist, we present a review of a closely monitored cohort assessed over 40 years. Methods: Retrospective observational study at University College London Hospital included patients fulfilling the 2016 ACR/EULAR criteria for SjD between 1986–2025. Patients with associated SjD were excluded. Associations between serological markers and clinical features were analysed using chi-square or Fisher’s exact tests (p < 0.05). Differences between ethnic groups were also assessed. Results: 283 patients were included, 93.3% female, with mean age at diagnosis of 50.1 ± 15.2 years and mean follow-up of 12.5 ± 8.6 years. Common manifestations were fatigue (61.5%), parotid swelling (30.5%), arthritis (25.8%), and Raynaud’s phenomenon (27.6%). Anti-Ro and anti-La antibodies were present in 75.7% and 45.2%, respectively; rheumatoid factor in 57.3%. Lymphoma developed in 9.9% (mostly non-Hodgkin MALT) and was associated with hypergammaglobulinemia (p = 0.03; RR = 2.56) and parotid swelling (p < 0.001; RR = 5.53). Serological markers correlated with systemic features including lymphadenopathy, vasculitis, and pulmonary involvement. Caucasian patients showed higher mortality (p < 0.001; RR = 3.89) and peripheral nervous system involvement (p = 0.02; RR = 2.18), and less ANA positivity (p = 0.004; RR = 0.88), anti-Ro (p = <0.001; RR = 0.77) and RF (p = 0.04; RR = 0.81) and hypergammaglobulinemia (p = <0.001; RR = 0.63) when compared with non-Caucasian patients. Conclusions: This long-term cohort confirms the strong association between B-cell activation markers and adverse outcomes in Sjögren’s disease. Hypergammaglobulinemia and parotid swelling emerged as key predictors of lymphoma, supporting their role in risk stratification. These findings reinforce the importance of long-term monitoring and may help guide personalized clinical management and surveillance strategies. Full article

Lysobacter antibioticus Hz25 is a novel strain that was isolated from the rhizosphere of the relict endemic plant Hedysarum zundukii Peschkova (Fabaceae), which grows on carbonate soils in the Baikal region of Russia. This work presents the complete genome sequence of Hz25 (5.98 Mb, 66.94% GC), which was obtained using a hybrid assembly method combining Oxford Nanopore and Illumina sequencing. Phylogenetic analysis based on 47 Lysobacter genomes and an average nucleotide identity (ANI) value of 96% confirmed its affiliation with L. antibioticus. A comparative pan-genome analysis with three closely related strains (13-6, 76, and ATCC 29479) identified 554 strain-specific genes. This significant genomic plasticity likely reflects adaptation to the sharply continental climate, high insolation, and low free iron content of the native soil. The genome encodes a comprehensive micropredator arsenal, including: seven chitinase genes (GH18 and GH19 families); bacteriolytic enzymes (Blp, L1, L4, Ami); a complete type III secretion system (T3SS) with predicted effectors; type IV pili (including the PilZ-PilB regulatory complex); and siderophore biosynthesis genes (lysochelin). The genome contains genes ars of an arsenic resistance system, but lacks the ACR3 efflux pump, suggesting that these genes may have alternative functions. Genes involved in calcium homeostasis (Excalibur domain, Na⁺/Ca²⁺ antiporter) were also identified. These features make Hz25 a promising candidate for biocontrol applications in cold climates and metal-contaminated environments. Full article

Milbemycin D is a promising 16-membered macrolide insecticide with reported superior efficacy, but its commercial development has been hindered by extremely low natural yields. This study aimed to construct a high-yielding microbial platform for milbemycin D production using combinatorial biosynthesis and advanced genome editing. An optimized CRISPR/Cas9-AcrIIA4 system was employed to seamlessly replace the aveA3 polyketide synthase (PKS) gene in the ivermectin B1b-producing strain Streptomyces avermitilis HU501 with the heterologous milA3 PKS from S. bingchenggensis. The engineered strain was validated genetically and metabolically, followed by high-throughput screening and fermentation optimization in various media. The biosynthesized compound was structurally confirmed by spectroscopy. Bioactivity was evaluated against Bursaphelenchus xylophilus, Hyphantria cunea, and Plutella xylostella. The engineered strain S. avermitilis HU501-M successfully shifted its major product to milbemycin D, reaching a final titer of 679.03 mg/L. Bioassays revealed that milbemycin D exhibited significantly enhanced potency, with LC₅₀ values 8–24% lower than those of milbemycin A3/A4. This work demonstrates an efficient CRISPR/Cas9-mediated PKS replacement strategy to achieve the high-yield production of milbemycin D, offering a promising microbial source and a generalizable framework for engineering complex polyketide pathways. This proof-of-concept establishes a foundation for future process development toward potential commercial application. Full article

Before the American Heart Association introduced the cardiovascular–kidney–metabolic (CKM) syndrome concept in 2023, clinical care was largely organ-specific. This retrospective study analyzed diagnostic patterns and gaps in 406 patients with hypertension referred to and evaluated at the University Hospital Basel Hypertension Centre in 2017, 2019, or 2022 to identify blind spots in the assessment of cardio–kidney–liver–metabolic health. Electronic health records were used to assess CKM-relevant diagnostics, including lipid profiles, N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography, kidney function (estimated glomerular filtration rate: eGFR, urinary albumin-to-creatinine ratio: uACR), and hepatic assessment (Fib-4 score, abdominal ultrasound). Previously undetected conditions were identified according to contemporary criteria for dyslipidemia, chronic kidney disease (CKD), suspected heart failure (HF), diabetes, and suspected metabolic dysfunction-associated steatotic liver disease (MASLD). Although 94% of participants had laboratory data, key CKM parameters were inconsistently assessed. Of the participants, 39% had neither NT-proBNP measurement nor echocardiography, and 27% lacked hepatic ultrasound or sufficient data for Fib-4 calculation. Previously unrecognized comorbidities were common (suspected HF 21%, CKD 6%, suspected MASLD 3%). Lipoprotein(a) testing increased from 0% in 2017 to 23.7% in 2022, indicating growing awareness. Despite specialized care, diagnostic fragmentation persisted, underlining the need for systematic, interdisciplinary screening and informing the design of prospective registries such as the Swiss CKLM Registry to integrate patient-centered cardio–kidney–liver–metabolic care. Full article

Cronobacter spp. is a pathogenic genus comprising seven species, of which C. sakazakii is particularly notable for its association with neonatal outbreaks linked to powdered infant formula. The severity of infections is associated with virulence factors (VFs) and β-lactam antibiotic resistance genes (ARGs). Next-generation sequencing (NGS) has enabled precise strain typing through core genome multilocus sequence typing (cgMLST), enhancing discrimination and accuracy. This study aimed to use cgMLST (2831 genes) to genomically characterize 34 Cronobacter strains which had been isolated from powdered milk and production surfaces between 2011 and 2022. The identified strains included C. sakazakii ST1, ST4, ST13, ST31 and ST83, as well as C. malonaticus ST60. Overall, there were eight clusters of closely related strains. All strains exhibited resistance to cephalothin, 18 were resistant to ceftazidime and 11 to ampicillin. Various resistance genes (bla_CSA, bla_CMA, fos, qacJ, marA, AcrAB-TolC, and mcr-9.1) and virulence genes (cpa, nanAKT, fic, relB, fliC) were detected, with some genes being exclusive to C. sakazakii. All strains carried plasmids and mobile genetic elements. The multidrug resistance and presence of virulence genes in these isolates highlight the significant risk that C. sakazakii-contaminated powdered dairy products pose to public health, underscoring the need to adopt proper hygienic manufacturing practices and effectively implement HACCP in their production. Full article

Background: The ambulatory arterial stiffness index (AASI) is a non-invasive surrogate marker of arterial stiffness; however, the relative contributions of hemodynamic, cardiometabolic, and renal factors to the AASI remain incompletely understood. This study aimed to identify the independent clinical factors associated with the AASI. Methods: This retrospective cross-sectional study included 290 individuals aged 18–65 years who underwent ABPM between 2020 and 2024. Participants were classified as hypertensive or normotensive based on ABPM criteria. Hemodynamic parameters, cardiometabolic indices, and renal biomarkers, including the urine albumin-to-creatinine ratio (uACR), were assessed. Results: Associations between the AASI and clinical variables were evaluated using the following correlation analyses and hierarchical multivariable linear regression models: Model 1-1b (hemodynamic), Model 2 (hemodynamic plus cardiometabolic) and Model 3 (hemodynamic plus cardiometabolic plus renal). The AASI was significantly higher in hypertensive individuals compared with normotensive controls. In correlation analyses, the AASI was positively associated with age, systolic blood pressure parameters, atherogenic lipid indices, and uACR and negatively associated with diastolic blood pressure parameters and the estimated glomerular filtration rate (eGFR). In multivariable regression analyses, age, maximum systolic blood pressure, and maximum diastolic blood pressure remained independently associated with the AASI across models. uACR was also independently associated with the AASI in the fully adjusted model. Conclusions: The AASI is primarily associated with hemodynamic load and age-related vascular changes. Among non-hemodynamic factors, albuminuria demonstrated the strongest association with the AASI after multivariable adjustment. These findings suggest the potential clinical value of the AASI as a practical marker for early cardiorenal risk assessment using routine ABPM data. Full article

There is a growing need to understand ciprofloxacin (CIP) resistance in less prevalent Salmonella serovars like Salmonella Dublin, which causes life-threatening conditions in both humans and animals. This study investigated potential factors contributing to CIP-resistance in a Salmonella Dublin isolate. The isolate was detected from an initial screening of 17 biobanked Salmonella isolates using the Kirby-Bauer disk diffusion (KBDF) method. The minimum inhibitory concentration (MIC) values of the identified CIP-resistant Salmonella Dublin isolate and a CIP-susceptible isolate of the same serovar were also obtained using the broth-dilution (BD) method. The two candidates were then challenged in 1/4 of their respective BD MICs for gene expression analysis, focusing on the acrAB efflux genes and the regulator genes marA, ramA, and soxS. Genomes of the isolates were also sequenced using the Oxford Nanopore sequencing platform, and then analyzed for mutations, antimicrobial resistance genes, and plasmids using ABRicate. The SWISS-MODEL server was used for protein modeling and comparison. For our results, the MIC values (KBDF; BD) for the CIP-resistant and CIP-susceptible Salmonella Dublin isolates were (1.5 μg/mL; 1.95 μg/mL) and (<0.125 μg/mL; 0.03 μg/mL), respectively. Both isolates had genes (mdtK, emrR, emrA, and emrB) notable for fluoroquinolone resistance, with the CIP-susceptible isolate also carrying the IncFII(S) plasmid. Expression of the acrA, acrB, ramA, and soxS genes was markedly higher in the CIP-resistant isolate, which also harbored an Asparagine (N) to Serine (S) mutation at position 868 in the GyrA protein. This mutation, however, caused no significant structural change. Despite reporting on a single CIP-resistant Salmonella Dublin isolate, our result highlights the potentially significant role of an efficient efflux system in contributing to CIP resistance in this isolate, even when no impactful mutations were identified. Full article

Heat stress poses a considerable challenge to the modern poultry industry by negatively impacting immune system maturation and eliciting inflammatory responses. Peroxisome proliferators-activated receptors α (PPARα), predominantly expressed in metabolically active tissues such as skeletal muscle, are essential for regulating the inflammatory process. Moreover, our recent research has found that heat stress down-regulates the transcription of PPARα in broiler chickens. To study if PPARα regulation is involved in heat-stress-induced skeletal muscle inflammatory response in broiler chickens, 180 male Arbor Acres (AA) broilers aged 22 days were randomly assigned to three experimental groups: a thermoneutral condition group at 21 °C, a heat stress group at 31 °C and a heat stress group at 31 °C supplemented with the PPARα activator fenofibrate. After 7 days of adaptive feeding, the broilers were subjected to a 14-day formal experimental phase. Results demonstrated that heat stress decreased the spleen and thymus index and increased serum and breast muscle inflammatory factor concentrations (p < 0.05). Moreover, heat-stress-induced abnormal breast muscle fiber morphology in broiler chickens. Furthermore, heat stress significantly up-regulated nuclear factor kappa-B (NF-κB) expression in boiler chickens (p < 0.05). However, activating PPARα through fenofibrate improved the growth performance (p < 0.05), enhanced immune organ indexes (p < 0.05), reduced inflammatory factor concentrations (p < 0.05), alleviated breast muscle fiber morphology damage and suppressed NF-κB expression (p < 0.05) in the breast muscle of broiler chickens. Based on our previous research, these results collectively underscore that heat stress induced inflammation and up-regulated NF-κB in the breast muscle of broiler chickens by inhibiting PPARα. Full article

Background/Objectives: The objective of this study was to evaluate the performance of Breast-SlimView^®, a deep convolutional neural network for the automatic classification of BI-RADS and breast density in MLO (mediolateral oblique) and CC (craniocaudal) views. Methods: A total of 9560 mammographic images from 2390 Mexican women (age: 54.14 ± 8.72 years) were labeled according to ACR (American College of Radiology) density (A-D) and BI-RADS 1, 2, and 3 (low risk), and BI-RADS 4 and 5 (high risk). All mammograms in the test dataset were blinded and read by two radiologists, and the consensus was taken as the reference standard. The accuracy, sensitivity, and specificity of the automated AI-based classification system was evaluated against the consensus reached by expert radiologists. Results: The classification of MLO and CC projections had a mean sensitivity of 0.81 (95% CI: 0.797–0.829), a specificity of 0.70 (95% CI: 0.686–0.722), and an accuracy of 0.71 (95% CI: 0.698–0.734) in differentiating between low and high risk. Good agreement was observed with ACR breast density classifications A, B, C, and D. Agreement between AI and human readers was “substantial” (Pearson’s chi-square, p = 0.001). Conclusions: AI enables accurate, standardized, observer independent classification. Full article

To dissect the molecular mechanisms underlying chicken cecal development, this study used Liangshan Yanying chickens (a local slow-growing breed) and Arbor Acres (AA) chickens (a fast-growing breed) as experimental models. Cecal tissues were collected from healthy chickens at 1, 14, and 28 days of age (n = 10 per breed per day of age) to measure cecal length and perform transcriptome sequencing. Through the screening of differentially expressed genes (DEGs), functional enrichment analysis, construction of protein–protein interaction (PPI) networks, and qRT-PCR validation, temporal changes in cecal development between the two breeds were systematically compared. Results showed that cecal length of both breeds increased significantly with age (p < 0.05), with significant differences between breeds. A total of 18 high-quality samples were obtained from transcriptome analysis (Q30 ≥ 93%), with a mapping efficiency of 86.2–90.5%. The number of DEGs was highest between 1 and 28 days of age (1844 DEGs in Liangshan Yanying chickens and 1747 DEGs in AA chickens), and the number of inter-breed DEGs reached 2133 at 28 days of age. A total of 70 DEGs with consistent expression trends were identified (22 upregulated and 48 downregulated), which were enriched in Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways such as “B cell activation”, “peptide transport”, and “bile acid metabolism”. qRT-PCR validation indicated that the expression trends of genes (e.g., CD79B, IRF4) were highly consistent with sequencing results (R² = 0.91). PPI network analysis suggested that SLC15A1, ACE, and ENPEP were key hub genes, forming a “transport–metabolism” synergistic module. This study reveals the temporal dynamics of chicken cecal development and the molecular basis of inter-breed differences, providing a theoretical foundation for broiler genetic improvement. Full article