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Thermal sensitivity and supply scaling effects on 7 nm FinFET based triple tail dynamic CMOS comparator for automotive/aerospace/electronics industrial applications
Fluorescent probes as markers of cell envelope structure and function in halophilic archaea
Abstract Prokaryotes, particularly those in extreme environments, are capable of diverse metabolic states resulting in altered cell envelope structure and function. However, these changes are difficult to assess as standard fluorescent probes are often incompatible with extreme conditions and/or extremophile cell physiology. Halophilic archaea present the challenge of near-saturated intra-/extra-cellular salts, high membrane potential, and extended survival in altered metabolic states including entrapment within salt crystal fluid inclusions. We evaluated the compatibility of six fluorescent markers of cell envelope stability and activity with two model species, Halobacterium salinarum and Haloferax volcanii . Redox activity markers alamarBlue and pure resazurin solutions, membrane potential probes MitoTracker Orange-CMTMRos and Rhodamine 123, and SYTO 9 and propidium iodide (LIVE/DEAD kit) to assess cell membrane integrity were evaluated for use in bulk (microplate reader) and cell-specific (microscopy) applications. Limitations of each probe were identified, clarifying the utilization of each based on cell physiology, growth phase, medium composition, and probe exposure time including extended timescales needed to simulate the environmental conditions of haloarchaea. Of particular note, propidium iodide behavior was unreliable leading to double-labeling of cells and false interpretation of cells as dead. These data provide important insights into the study of prokaryotes in non-standard conditions.
Sustainable gold nanoparticles using Jania rubens, targeted therapeutic potential in prostate cancer and mechanistic insights via GO/KEGG pathway analysis
Abstract Gold nanoparticles (AuNPs) are highly versatile nanomaterials due to their exceptional physicochemical and biological properties with promising biomedical applications. This study presents a rapid, eco-friendly biosynthesis of AuNPs using the red alga Jania rubens (Jan-AuNPs). GC analysis of the algal extract revealed a total fatty acid content of 1.41 mg/g DW, dominated by saturated fatty acids primarily methyl palmitate (53.22%) and methyl stearate (27.89%) alongside methyl oleate (9.42%). Phytochemical profiling demonstrated a rich biochemical composition, including a high total phenolic content of 299.82 ± 1.83 mg GAE/g DW, total flavonoid content of 35.61 ± 0.52 mg QE/g DW, and total carbohydrate content (TCC) of 166 ± 1.05 mg GE/g DW, collectively conferring potent reducing, capping and stabilizing capacities of the algal extract in mediating Jan-AuNPs biosynthesis. Formation of Jan-AuNPs was visually confirmed by a color change from pale yellow to ruby red or pinkish-red, which was further confirmed by UV–vis spectroscopy with a surface plasmon resonance (SPR) peak at 549 nm. TEM analysis revealed predominantly spherical particles with an average diameter of 16.26 nm, with a few rod-shaped particles also detected. The crystalline nature of Jan-AuNPs was validated by XRD and SAED analyses. Zeta potential measurements revealed a surface charge of -28 mV, indicating good colloidal stability. FTIR analysis confirmed the active involvement of diverse algal biomolecules in the formation and stabilization of Jan-AuNPs. Biosynthesis conditions were optimized using face-centered central composite design (FCCCD), achieving the highest yield of 289 µg/mL at pH 7, 60 °C, 3 h incubation, and 300 µg/mL gold ion concentration. In silico predictive analysis identified cancer-associated gene targets modulated by AuNPs, thereby predicting prostate cancer (PC) as the malignancy with the highest therapeutic susceptibility for AuNPs-based interventions. Experimental validation confirmed potent and selective antitumor activity against PC3 prostate cancer cells in vitro (IC 50 = 6.39 µg/mL; SI = 15.24) with minimal cytotoxicity toward normal HFB4 cells (IC 50 = 97.41 µg/mL). In vivo evaluation using the Ehrlich ascites carcinoma (EAC) model in Swiss albino mice demonstrated that combined treatment with Jan-AuNPs and doxorubicin achieved a tumor growth inhibition of 97.33%. These findings establish Jania rubens -mediated biosynthesis as a sustainable and scalable platform for producing bioactive AuNPs and highlight the pivotal role of bioinformatics in guiding experimental cancer nanomedicine research. The results highlight Jan-AuNPs as a promising, safe, and multi-targeted nanotherapeutic candidate with significant potential for the management of prostate cancer.
Psychiatric morbidity among medical clinic attendees at a tertiary care hospital in Sri Lanka during the economic crisis
Mobility and environmental availability of metal(loid)s at a historically recultivated Cu/Pb smelter site in Polichno, Holy Cross Mountains, Poland
Abstract This study investigates the long-term effects of partial recultivation on metal(loid) contamination and environmental risks at the historical (14-17th century) Cu–Pb smelting site at Polichno (Holy Cross Mountains, Poland). More than 50 years ago, the site underwent partial recultivation involving slag removal; however, residual slag fragments remain dispersed throughout the soil profile. The slag contains high mean concentrations of metal(loid)s, including 111,000 mg·kg − 1 Pb, 56,300 mg·kg − 1 Ba, 8370 mg·kg − 1 Zn, 465 mg·kg − 1 Cu, 110 mg·kg − 1 As, mainly hosted in sulfides, arsenides, sulfates, and a glassy matrix. Maximum soil concentrations reached 7010 mg∙kg − 1 Pb, 4180 mg∙kg − 1 Ba, 1500 mg∙kg − 1 Zn, 658 mg∙kg − 1 Cu, 45.4 mg∙kg − 1 As, with the highest levels in ash- and wood-containing horizons. Average pore water concentrations were 115 µg∙l − 1 Pb, 166 µg∙l − 1 Ba, 161 µg∙l − 1 Zn, 58.9 µg∙l − 1 Cu, and 1.9 µg∙l − 1 As. Batch leaching tests using deionized water classified the slag as non-hazardous waste rather than inert waste, as Pb release exceeded the regulatory threshold for inert waste. pH-static tests showed peak mobilization at pH 2 (Ba 39,000 mg·kg − 1 , Pb 4860 mg·kg − 1 , Zn 3870 mg·kg − 1 , As 21.7 mg·kg − 1 ), with minima at neutral pH. The formation of secondary phases during leaching indicates immobilization processes that limit metal(loid) mobility.
Scalable risk stratification of undiagnosed heart failure using routine health data and its association with imaging phenotypes and outcomes
Abstract Late diagnosis of Heart failure (HF) is associated with worse outcomes. We aimed to develop a scalable tool to identify those at high risk of undiagnosed HF using routine electronic health records (EHR). We developed and internally validated a logistic regression (FIND-HF) model for incident HF diagnosis within one year in United Kingdom primary care EHRs (CPRD-Aurum, n=3 520 186), with good prediction performance (area under the receiver operating characteristic curve (AUC) 0.79), equal to more complex modelling techniques. We externally validated FIND-HF in United Kingdom (CPRD-GOLD, n=570 850, AUC 0.72), Japan (JMDC, n=6 820 694, AUC 0.73), United States of America (Epic Cosmos, n=7 710 398, AUC 0.78), and Taiwan (NTUH, n=170 518, AUC 0.85). In a cohort who had undergone HF diagnostics an optimised FIND-HF threshold had a positive predictive value of 21.4% and a negative predictive value of 96.9%. Amongst patients with HF who had undergone cardiac magnetic resonance imaging, high FIND-HF risk compared with low FIND-HF risk as reference, was associated with increased risk of a primary composite outcome of heart failure hospitalisation or cardiovascular death and more advanced adverse remodelling including lower left ventricular ejection fraction. FIND-HF is a scalable EHR-based model which has the potential to help rule out undiagnosed HF in low risk cases, whilst high risk cases are associated with more advanced cardiac dysfunction and worse prognosis.
An ultra high-gain switched-capacitor-inductor DC–DC converter with reduced voltage stress
Essential role for the urothelial plaque in Gram-negative urinary tract infections
Cosmic-ray modified flows with effective wave damping
Associations between the intratumoral microbiome and the host transcriptome in bladder cancer and their implications for prognostic prediction
Detection of congeners and contaminants in commercial and homemade alcoholic beverages under varying temperatures using metal-phenolic film-coated quartz crystal microbalances
Association of nurse-led targeted sedation-analgesia management with ventilation duration and sedation quality in mechanically ventilated patients
Purpose Variability in sedation–analgesia assessment and titration is common in mechanically ventilated ICU patients and may contribute to unnecessary deep sedation and delayed ventilator liberation. This study examined the association between a nurse-led targeted sedation-analgesia management workflow and clinical outcomes in an Intensive Care Unit (ICU). Methods This single-center retrospective observational cohort study was conducted and reported in accordance with the STROBE statement. Adult patients receiving invasive mechanical ventilation for ≥24 hours in the ICU from January 1, 2024 to December 31, 2025 were included. Patients were classified into a usual-care group (physician-directed care) or a nurse-led targeted management group using prespecified documentation-based operational criteria, including daily RASS targets, assessment frequency, nurse-driven titration, and closed-loop reassessment. Primary outcomes were duration of invasive mechanical ventilation and sedation target attainment (proportion of RASS assessments within target). Secondary outcomes included deep sedation exposure (RASS ≤ −3), agitation exposure (RASS ≥ +1), ICU length of stay, delirium, unplanned extubation, reintubation within 48 hours, tracheostomy, and 28-day mortality. Results A total of 102 patients were analyzed (usual-care group, n = 48; nurse-led group, n = 54). The nurse-led group had shorter mechanical ventilation duration (4.3 [3.2–6.3] vs 5.9 [4.3–8.7] days; P < 0.01) and higher sedation target attainment (74.0% ± 11.5% vs 61.5% ± 12.8%; P < 0.01). Deep sedation exposure and agitation exposure were lower in the nurse-led group (16.1% ± 9.1% vs 27.6% ± 10.9%; P < 0.01, and 9.1% ± 6.0% vs 12.4% ± 7.3%; P = 0.03, respectively), and ICU length of stay was shorter (8.0 ± 4.2 vs 9.7 ± 4.9 days; P = 0.02). Delirium was numerically lower but not statistically significant (22.22% vs 35.42%; P = 0.19), and no significant differences were observed in unplanned extubation, reintubation within 48 hours, tracheostomy, or 28-day mortality. After adjustment, nurse-led targeted management was associated with shorter ventilation duration (adjusted ratio, 0.79; 95% CI, 0.67–0.93; P = 0.004), whereas the association with delirium was not significant (adjusted OR, 0.58; 95% CI, 0.26–1.30; P = 0.190). Conclusion In this retrospective cohort study, nurse-led targeted sedation-analgesia management was associated with higher sedation target attainment, lower exposure to deep sedation and agitation, shorter invasive mechanical ventilation duration, and shorter ICU stay. No increase in measured safety events was detected. Given the retrospective design, small sample size, and limited adjustment, these findings should be interpreted as associations rather than evidence of causal effectiveness.
Spatiotemporal variability of physicochemical parameters, heavy metals and associated ecological and human health risks assessment in Rapti River Basin, India
A role for nucleosome remodellers during resection of deprotected telomeres in yeast
DNA double-strand break (DSB) repair pathway choice is strongly influenced by DNA end resection, a process in which the 5′ DNA strand is degraded to generate 3′ single-stranded DNA required for homologous recombination. Although the enzymatic mechanisms of resection have been well defined, its regulation by the dynamic chromatin environment surrounding the DNA break remains less clear. Here, we used the budding yeast cdc13-1 system to analyse DNA end resection after telomere deprotection. Inactivation of Cdc13, a component of the CST (Cdc13–Stn1–Ten1) telomere-capping complex, exposes telomeric DNA ends and triggers a DNA damage response. Using this system, we examined the contribution of long-range resection nucleases and chromatin regulators. Analysis of long-range resection nucleases revealed that the Dna2 nuclease contributes to telomeric processing, particularly in the absence of the exonuclease Exo1. Genetic removal of chromatin regulatory factors showed that H2A.Z, a histone H2A variant incorporated by the SWR1 complex, did not significantly affect resection, whereas depletion of the major nucleosome eviction complexes RSC and SWI/SNF impaired resection after telomere deprotection. Together, these results indicate that nucleosome eviction allows for efficient resection at deprotected telomeres and the analogies to long-range resection at DSBs illustrate the utility of the cdc13-1 system for studying long-range resection in broader context.
Neurocognitive effects of guided moving meditation on divergent thinking and neural coherence in agri-entrepreneurs: An EEG study
Bioinformatics analysis reveals the association of bile acid metabolism-related genes with sepsis
Background Sepsis, is a life-threatening syndrome triggered by infection. Bile acid metabolism may be involved in the pathogenesis of sepsis, the underlying association has not yet been elucidated. Thus, we aimed to screen for bile acid metabolism-related biomarkers of sepsis and discover the potential association. Methods Sepsis-related datasets were downloaded from the Gene Expression Omnibus (GEO) database. We identified differentially expressed genes (DEGs) and bile acid metabolism-related differentially expressed genes (BAMRDEGs), then identified hub genes using protein–protein interaction (PPI) network analysis and CytoHubba algorithm. After GO/KEGG enrichment analysis, a sepsis risk prediction model based on key genes was subsequently constructed using support vector machine recursive feature elimination (SVM-RFE) machine learning and least absolute shrinkage and selection operator (LASSO) regression. CIBERSORTx analysis was performed to assess immune cell infiltration and its association with key genes. Finally, the transcriptional levels of key genes in sepsis samples were detected by Quantitative Real-time PCR (qRT-PCR). Results 9785 DEGs were identified, including 5138 upregulated and 4647 downregulated genes. Additionally, 25 hub genes were identified. Gene enrichment analysis indicated that the hub genes participate in multiple biological pathways. Key genes ( ABCC2 , PECR , EPHX2 , PEX2 , and AGXT ) exert central roles in the development of sepsis, indicating the involvement of bile acid metabolism. Significant correlations existed between the expression of key BAMRDEGs and the levels of different immune cell types. qRT-PCR suggested significant up-regulation on ABCC2 and AGXT in sepsis samples versus controls. Conclusion This study revealed novel insights into the correlation between sepsis and bile acid metabolism, and identified 5 key genes involved in the development of sepsis, providing molecular targets and novel strategies for the diagnosis and treatment of sepsis.
The baseline vitreous proteome in rhegmatogenous retinal detachment: a case–control study of proliferative vitreoretinopathy
Benefits of hypocrisy: Do managers gain more from greenwashing
This study finds that corporate greenwashing raises executive compensation. Mechanism analysis indicates that greenwashing enhances executive compensation by improving short-term performance and enhancing executive reputation. In addition, this effect is more pronounced in non-state-owned enterprises, companies with equity incentive plans, and firms that grant restricted stock.
HIV self-testing in Argentina: acceptability and use of an oral-based test among men who have sex with men (MSM)
Exploring the predictability of distributed lag nonlinear models using SARS-CoV-2 wastewater-based surveillance in multiple communities in Alberta, Canada
Background Wastewater–based surveillance can be an important part of pandemic management, especially when testing capacity of individuals is limited. Statistical modeling can be used to examine the relationship between wastewater pathogen levels and clinical cases. The objective of this study was to examine the utility of distributed lag nonlinear modeling to derive the relationship between wastewater SARS-CoV-2 RNA levels and COVID-19 clinical cases across communities in Alberta, Canada when clinical testing was comprehensive. Methods This retrospective cohort study used data from 24-hour composite wastewater collected and tested two to three times per week from 11 wastewater treatment plants (WWTPs) in Alberta, Canada during May 10, 2020, to March 15, 2022. The number of daily new cases of COVID-19 downloaded from Alberta Health’s centralized dataset of clinical surveillance of COVID-19 were mapped to each sewershed. Distributed lag nonlinear models were fit to describe the exposure-response relationship between the 7-day rolling average of SARS-CoV-2 RNA and daily new cases for each WWTP separately. Results The 11 WWTPs served a population of 3,422,062 (77% of Alberta’s population) and 386,528 cases were documented during the study period. From 2021 onward, peaks in both wastewater viral RNA levels and cases tracked reasonably well. For almost all WWTPs, the best fitting model was a Poisson additive model with a P-spline for time. Models for the larger communities had better fits than smaller communities as represented by adjusted pseudo-R 2 ranging from 80.7% to 94.4%. Models followed the same general trends as the actual COVID-19 cases over time. Conclusions With relationships between wastewater viral RNA levels for SARS-CoV-2 and COVID-19 cases expected to vary over time and to be non-linear, distributed lag nonlinear models are promising. While the form of the models was similar across WWTPs, the resulting estimates were different among sites suggesting site-specific analyses are essential.