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Dose‑dependent association of smoking exposure with HDL subfraction cholesterol content
Abstract Smoking has a significant effect on plasma lipid concentrations, especially high‑density lipoprotein (HDL)-associated cholesterol and its distribution across HDL subfractions, which are critical for cardiovascular health. The present study aimed to investigate the association between smoking and HDL‑cholesterol (HDL‑C) concentration, as well as the cholesterol distribution between different HDL subfractions, and other lipid parameters, including total cholesterol (TC), low‑density lipoprotein cholesterol (LDL‑C), triglycerides (TG), apolipoprotein AI (ApoAI), apolipoprotein B100 (ApoB100), and the TG/HDL‑C and ApoB100/ApoAI ratios, in a Hungarian cohort of 314 (137 nonsmokers and 177 smokers). HDL‑associated cholesterol was fractionated into ten electrophoretic subfractions (HDL‑1 to HDL‑10) and three subclasses (HDL‑L, HDL‑I, HDL‑S) using the Lipoprint ® HDL system. Smoking exposure was characterized using five indicators: current smoking status, cigarettes per day (CPD), duration of smoking (DoS), pack‑years, and the Heaviness of Smoking Index (HSI). Multiple regression models were applied, and significance was defined as p < 0.05 after Benjamini–Hochberg correction. All smoking‑related indicators were associated with a decrease in the cholesterol content of HDL subfractions. The strongest associations were observed for HDL‑4, HDL‑5, HDL‑6, and HDL‑7 ( p < 0.001–0.033), as well as for the HDL‑I subclass ( p < 0.001). Regarding the broader lipid profile, all indicators were significantly associated with lower HDL‑C ( p < 0.001) and ApoAI ( p = 0.001–0.003), and higher TG ( p = 0.012–0.036), TG/HDL‑C ratio ( p < 0.001–0.004), and ApoB100/ApoAI ratio ( p < 0.001–0.015). In conclusion, smoking significantly reduces the cholesterol content of HDL subfractions, particularly within HDL‑4 to HDL‑7 and the HDL‑I subclass. Although total cholesterol levels were not significantly altered, smoking induced an atherogenic shift in lipid composition by lowering HDL‑C and increasing TG levels, which may contribute to or accelerate the development of atherosclerosis.
Statewide multi-year wastewater sequencing reveals dual origins of HIV-1 signal
Abstract Human immunodeficiency virus 1 (HIV-1) is a retrovirus which has infected 90 million people and resulted in over 40 million deaths. Despite advances in diagnostics, treatment, and prophylaxis, HIV-1 continues to spread due to undiagnosed and untreated infections. Traditional monitoring methods are ineffective when access to testing is limited or people do not seek care, particularly given the long period between infection and symptom onset, allowing undetected transmission to continue. Here, we use a hybrid-capture sequencing approach to track HIV-1 signal in municipal wastewater in 15 different cities over nearly 3 years. We obtain near-complete genomic coverage of HIV-1, enabling detailed genomic analysis. Surprisingly, there are a substantial number of research-associated retroviral vector sequences recovered. Using computational competitive mapping, we identify specific genomic regions that differentiate authentic HIV-1 from vector-derived inputs. In an exploratory analysis of sites with available clinical data, wastewater-derived circulating HIV-1 reads show a positive correlation with community-level HIV diagnosed prevalence that was robust to exclusion of individual high-prevalence sites. This study identifies lentiviral vector contamination as a confounding factor in wastewater HIV-1 detection, recovers authentic circulating HIV-1 signal through an original classification framework, and provides initial evidence that the resulting signal tracks community HIV burden.
Metrnl ameliorates ulcerative colitis by inhibiting NLRP3 inflammasome activation via ASC
Transferrin receptor 1 binds human parvovirus B19 VP1u to facilitate entry
Abstract Human parvovirus B19 (B19V) displays a strict tropism for erythroid progenitor cells, which is governed by the VP1 unique domain (VP1u). This domain mediates cell-specific uptake through interaction with an unknown cellular receptor, termed VP1uR. Proximity labeling in permissive erythroid cells identifies transferrin receptor 1 (TfR1/CD71) as a predominant membrane protein associated with VP1u. VP1u constructs colocalize with TfR1 at the cell surface of erythroid cells. Incubation with anti-TfR1 antibody OKT9 abolishes binding and uptake of recombinant VP1u. While OKT9 efficiently inhibits B19V uptake and infection, it does not block virus binding to host cells. Direct binding assays confirm interaction of VP1u with human TfR1. Using cryo-EM we solved the 2.4 Å structure of the TfR1-VP1u complex, mapping the binding site. These findings establish TfR1 as the previously unknown receptor, VP1uR, required for B19V uptake.
AI is taking on antibiotic resistance — here’s how
Health-related quality of life in patients with psoriasis eligible for biologic therapy in southern Iran via the EQ-5D-5 L and DLQI
Abstract Psoriasis is a chronic inflammatory skin disease that can substantially impair health-related quality of life (HRQoL). While biologic therapies are widely used in patients with psoriasis, their real-world impact on HRQoL within biologic-eligible patient populations remains insufficiently explored, particularly in resource-constrained settings. This cross-sectional study assessed HRQoL in adult patients with psoriasis in Iran who were considered clinically eligible for biologic therapy according to Iranian treatment guideline criteria. HRQoL was assessed via the EQ-5D-5 L, EQ-VAS, and Dermatology Life Quality Index (DLQI). Multiple linear and logistic regression analyses were conducted to identify sociodemographic and clinical factors associated with HRQoL. The mean scores were 0.51 (EQ-5D-5 L), 59.7 (EQ-VAS), and 11.9 (DLQI). A lower HRQoL was significantly associated with greater disease severity, infliximab use, less than six years of education, lack of supplementary insurance, disease duration ≤ 5 years, and being married. Multivariate analysis confirmed the independent effects of these variables. The most commonly reported issues were pain/discomfort (78.5%) and anxiety/depression (75.9%). Patients with psoriasis eligible for biologic therapy in southern Iran experienced poor HRQoL. These real-world findings highlight the need for patient-centered approaches and policy reforms that enhance insurance coverage, improve health literacy, and ensure equitable access to psoriasis care in resource-constrained settings.
Designing effective single-molecule electromagnets with radially π-conjugated carbon structures
How AI is reshaping discovery in maths and physics
BioActive packaging materials based on pectin/curdlan gum and Pau d’Arco extract with pro-health properties as a solution for food industry
Abstract In the present study, bioactive packaging materials based on polysaccharides were developed and qualified by the WHO/FAO Expert Committee as safe food additives. Pau d’Arco extract was incorporated due to its rich bioactive composition and strong antioxidant properties. The addition of the extract conferred significant antioxidant activity to the polymer films. The colour of the films varied significantly (p < 0.05) depending on the extract concentration, which itself exhibited a dark colour. The highest barrier performance in terms of water vapour transmission rate (WVTR) and oxygen transmission rate (OTR) was observed for the sample with the highest extract content (2.5F). Changes in WVTR were associated with the presence of polyphenols and flavonoids in the extract. Furthermore, the films displayed concentration-dependent antibacterial effects against E. coli , with higher extract levels leading to longer inhibition times, indicating enhanced antimicrobial activity. Spearman’s correlation confirmed that antioxidant activity parameters and the total polyphenol and flavonoid content were fully correlated with OTR and WVTR (R = 1), as well as with other measured properties, demonstrating the multifunctional potential of these bioactive films.
Nanozyme-engineered liners for proactive prevention of wear particle-induced osteolysis
Targeted next-generation sequencing implementation in Eswatini identifies rifampicin and bedaquiline resistance undetected by routine diagnostic testing
Abstract In Eswatini, multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains harbouring the rifampicin-resistance (RR) rpoB I491F mutation are missed by routine diagnostics, including GeneXpert MTB/RIF Ultra (Xpert Ultra), line probe assays (LPA), and mycobacterium growth indicator tube (MGIT) phenotypic drug susceptibility testing (pDST). To address this diagnostic gap, Eswatini introduced targeted next-generation sequencing (tNGS) in 2019. We analysed 234 patient samples enrolled from June 2021 to December 2024 with isoniazid and/or rifampicin resistance detected by routine diagnostics, or suspected treatment failure, and obtained detailed clinical and outcome data from 59 patients. tNGS detected RR in 159 strains, of which 101 (64%) carried the rpoB I491F mutation. Bedaquiline (BDQ) resistance, conferred by Rv0678 mutations, was identified in 87 strains, rendering 55% (87/159) of RR and 85% (86/101) of rpoB I491F strains genotypically BDQ-resistant. Routine tests substantially under-classified resistance, particularly in strains reported as isoniazid-resistant and rifampicin-susceptible. tNGS-informed treatment changes occurred in 53% (31/59) of patients, with 88% (52/59) treatment success. tNGS is therefore an essential tool to detect rpoB I491F “diagnostic escape” strains with additional BDQ resistance, and underscores the urgent need to reconsider current BPaLM regimens and global drug-resistance classifications.
Cortex-specific inversion of visual responses during sleep
Bacterial targeting of the neutrophil inhibitory receptor LILRB3 to evade antibody immunity
Abstract Antibody-mediated responses are critical for antibacterial immunity, driving Fc receptor-mediated phagocytosis, respiratory burst, and bacterial killing. Inhibitory immune receptors regulate cellular activation and immune homoeostasis, but whether they are targeted to evade antibody-mediated responses is unclear. Here, we show that the highly expressed inhibitory LILRB3 receptor on neutrophils is targeted by Streptococcus agalactiae to suppress antibody-driven defence. We show that the surface-localised β protein of S. agalactiae bound to LILRB3 and induced its cross-linking. β and LILRB3 interactions suppressed Fc receptor-mediated antibacterial responses such as respiratory burst and bacterial killing, inhibiting antibody-dependent bacterial killing by neutrophils. Moreover, β expression and LILRB3 targeting are associated with S. agalactiae lineages that cause invasive diseases in older adults, indicating that targeting inhibitory receptors most likely provides an immune evasion mechanism when antibody responses are waning, such as in immunocompromised or elderly individuals. Altogether, these results highlight a simple and important mechanism that bacterial pathogens utilise to overcome effective antibody-driven phagocyte responses.