Search Results (151)

The antimicrobial resistance crisis necessitates novel therapeutics. Selenium nanoparticles (SeNPs) offer promise, but their precise bactericidal mechanism remains poorly defined. This study aimed to define the antibacterial action of SeNPs synthesized via a green method with ascorbic acid and sodium citrate. The resulting SeNPs were monodisperse (17.8 ± 0.66 nm), crystalline, and highly stable (zeta potential: −69.9 ± 4.3 mV), exhibiting potent bactericidal activity against multidrug-resistant E. coli. To generate a mechanistic hypothesis, we integrated phenotypic analyses with a preliminary, single-replicate proteomic profiling. Recognizing this as an exploratory step, we focused our analysis on proteins with the most substantial changes. This revealed a coherent pattern of a targeted dual assault on core cellular processes. The data indicate that SeNPs simultaneously induce oxidative stress while severely depleting key components of the primary antioxidant glutathione system; key detoxification enzymes—glutathione S-transferase and glutaredoxin 2—were depleted 18- to 19-fold, while the stress protein HchA was reduced by over 63-fold. Concurrently, the patterns point toward a crippling of central energy metabolism; iron–sulfur enzymes in the TCA cycle, including aconitate hydratase (8.1-fold decrease) and succinate dehydrogenase (13.9-fold decrease), were severely suppressed, and oxidative phosphorylation was impaired (e.g., 4.7-fold decrease in NADH dehydrogenase subunit B). We propose that this coordinated disruption creates a lethal feedback loop leading to metabolic paralysis. Consequently, this work provides a detailed and testable mechanistic hypothesis for SeNPs action, positioning them as a candidate for a potent, multi-targeted antimicrobial strategy against drug-resistant pathogens. Full article

The therapeutic clotting factor VIII (FVIII) is known for its particular immunogenicity, with nearly 30% of hemophilic patients developing neutralizing antibodies against the infused protein. The root cause of this immunogenicity is still not well understood, but intrinsic factors, such as FVIII byproducts, have been linked to the immunological response elicited. Bioengineering of the FVIII molecule has been improving its recombinant (rhFVIII) production in many aspects, mainly enhancing its expression and stability. Assessment of immunogenicity for novel recombinant isoforms is crucial for further development and scaling-up processes, particularly due to the unpredictable antigenic properties and their impact on neutralizing antibody formation. In the present study, we describe a bioengineered human recombinant FVIII (rhFVIII-H6A), which induces lower immunogenicity in a murine model of hemophilia A. The rhFVIII-H6A product is characterized by a B-domain-deleted heavy chain (HCh), with the C-terminal of the B-domain fused to the light chain (BΔ-LCh). Compared to plasma-derived FVIII (pdFVIII) and rhFVIII reference products, treating hemophilic mice with rhFVIII-H6A induced lower levels of anti-FVIII antibody formation, including those with inhibitory neutralizing activity, while no difference was observed in the functional activity of rhFVIII-H6A in reverting the in vivo hemophilia phenotype. In addition, our results indicate that deleting the major part of the B-domain from the HCh might lower the immunogenicity of novel rhFVIII products. Full article

Tight sandstone gas constitutes a strategically significant resource in the exploration of unconventional hydrocarbon systems. Current understanding of the geochemical composition and genesis of tight sandstone gas in the Daning–Jixian Block, southeastern Ordos Basin, is insufficient, which hampers a comprehensive assessment of its resource potential. This study is the first to systematically investigate the geochemical characteristics and genetic origin of high-maturity tight sandstone gas in the southeastern Ordos Basin’s Daning–Jixian Block. Gas specimens were systematically acquired from multiple stratigraphic units within the reservoir interval and subjected to compositional and carbon–hydrogen isotope analysis. Compared with other gas fields in the Ordos Basin, the Daning–Jixian Block has higher average methane concentration, and notably lower ethane and propane concentrations; its average δ¹³C₁ and δ²H-CH₄ is heavier, while δ¹³C₂ and δ¹³C₃ are lighter. Based on the δ¹³C₁-δ²H-CH₄ diagram, all gas samples from the block and other basin gas fields fall into the geothermal, hydrothermal and crystalline gas domain, indicating gas genesis associated with over-mature organic matter interacting with external hydrogen. Milkov genetic diagram analysis reveals that the natural gas consists of primarily early-stage kerogen-cracking gas, with a minor contribution from crude oil-derived gas originating from Carboniferous–Permian source rocks. Notably, samples from Daning–Jixian exhibit a unique δ¹³C₁ > δ¹³C₂ reversal, attributed to mixing effects between gas from highly mature kerogen and gas from secondary cracking of crude oil. Consequently, ethane carbon isotopes alone are insufficient for definitive genetic classification. These findings provide a new geochemical interpretation framework for analogous high-maturity tight gas reservoirs. Full article

A manganese dioxide-modified carboxylated graphene oxide (MnO₂@CGO) nanocomposite was fabricated and utilized as a solid nanosorbent for extracting six organochlorine pesticides from environmental water samples. The target compounds, Hexachlorobenzene (HCB), β-Hexachlorocyclohexane (β-HCH), Heptachlor, Aldrin, Dieldrin, and o,p-Dichlorodiphenyltrichloroethane (o,p-DDT), were determined by micro-solid phase extraction (µ-SPE) coupled with gas chromatography–mass spectrometry (GC-MS) in selective ion monitoring mode. Key experimental factors influencing the extraction performance, such as sample pH, sorbent dosage, type and volume of eluting solvent, and time for desorption, were systematically optimized. Under the optimized conditions, the method showed good linearity (R² = 0.998–1.000) within the concentration range of 0.1–5 ng L⁻¹. The developed procedure was successfully applied to Nile River, agricultural wastewater, and groundwater samples, achieving recoveries between 87.1% and 101.2% with RSDs below 4.0%. The detection limits were 0.005–0.010 mg L⁻¹ at a signal-to-noise ratio of 3.0. Overall, the MnO₂@CGO-based µ-SPE method offers a sensitive, reliable, and straightforward approach for monitoring trace levels of organochlorine pesticides in environmental waters. Full article

Occupational exposure to soil-borne pesticides remains a critical safety and process-management challenge in industrial and agro-industrial settings. This work proposes a process-integrated analytical workflow that couples comparative instrumental identification of soil xenobiotics with an occupational risk assessment framework. We comparatively evaluate GC-MS (gas chromatography–mass spectrometry), HPLC (high performance liquid chromatography), FTIR (Fourier-Transform Infrared Spectroscopy), LC-MS/MS (Liquid Chromatography coupled with tandem Mass Spectrometry), and ICP-MS (Inductively Coupled Plasma Mass Spectrometry) against matrix complexity, sensitivity, cost, and throughput, and implement the Quick, easy, cheap, effective, rugged, safe (QuEChERS) method-based sample preparation followed by GC-MS and LC-MS/MS to demonstrate applicability on representative soil and food-chain samples. Complementary risk tools (toxicity–probability matrices, exposure pathway diagrams) and an integrated monitoring scheme that combines environmental data with biomonitoring are used to link concentrations to exposure potential and control priorities. In a soil case sample, low-level organochlorines were detected with total DDT at 0.010 mg/kg and total HCH at 0.003 mg/kg, illustrating how analytical outputs feed decision matrices for prioritizing interventions. Case analyses from agricultural and industrial contexts indicate that targeted substitution, optimized application, ventilation and dust control, PPE (personal protective equipment) adherence, and worker training can measurably reduce symptoms and biomarkers of exposure. Overall, a complementary, process-analytical approach—integrating sensitive multi-technique detection with exposure assessment and continuous monitoring—supports proactive risk management and aligns with process systems and monitoring themes. Recommendations include standardizing workflows, coupling routine environmental monitoring with biomonitoring where feasible, and embedding preventive policies and training into industrial management systems. Full article

This study investigates the presence of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in 165 yogurt samples collected from farms across 11 Lebanese regions. As the first nationwide assessment of these contaminants in yogurt, it addresses a critical gap in Lebanon’s food safety monitoring. Levels of PCBs, ΣDDTs, ΣHCH, HCB, endosulfan, methoxychlor, and dieldrin were quantified, revealing widespread contamination. A total of 40.6% of samples recorded total PCB concentrations exceeding European maximum residue limits (MRLs), with a national mean of 39.26 ng/g fat. Keserwan, and North and South Lebanon showed the highest PCB contamination, likely linked to thermal power generation activities. For OCPs, mean concentrations of all tested compounds exceeded their respective MRLs across all regions. Levels of ΣDDTs surpassed the MRL in 100% of samples with the highest mean concentration at 376.79 ng/g fat, followed by endosulfan (70.32 ng/g fat) and β-HCH (65.32 ng/g fat). Elevated OCP levels were especially noted in Bekaa, Baalbek-Hermel, and South and North Lebanon, likely reflecting intensive agricultural practices and the ongoing use of contaminants. Estimated daily intakes (EDIs) indicated potential dietary exposure risks, particularly from PCBs, ΣDDTs, and ΣHCH. These findings underscore the urgent need for regulatory oversight and national food safety monitoring to ensure public health protection. Full article

Sorting and isolating specific cells from heterogeneous populations are crucial for many biomedical applications, including drug discovery and medical diagnostics. Conventional methods such as Fluorescent Activated Cell Sorting (FACS) and Magnetic Activated Cell Sorting (MACS) face limitations in throughput, cost, and the ability to separate subtly different cells. Cell partitioning in Aqueous Two-Phase Systems (ATPSs) offers a biocompatible and cost-effective alternative, particularly when combined with continuous-flow microfluidics. However, it remains challenging to rationally design microfluidic ATPS devices and operation to separate cells with similar origin but different phenotypes. In this paper, using a model ATPS, polyethylene glycol (PEG)—Dextran (Dex) system, and model cells, human chondrocytes (hChs), and carboxylated polystyrene (PS) microparticles, we systematically characterized the material properties affecting cell partitioning in ATPSs, such as surface energies of the solutions and cells and solution viscosities. We developed an energy balance approach between interfacial energy and viscous dissipation to estimate the interface translocation dynamic of cells partitioning into the preferred phase. Combining the experimental measurement and the energy balance model, our calculation reveals that the time required for complete cell partitioning at the ATPS interface can be exploited in microfluidic ATPS devices to separate hChs with different phenotypes (healthy and diseased). We expect our dynamic energy approach to provide a basis and a design strategy for optimizing microfluidic ATPS devices to achieve the efficient separation of phenotypically similar cell populations and further expand the potential of microfluidic cell separation. Full article

Human coronaviruses are a group of viruses that continue to threaten human health. In this study, we investigated the antiviral activity of 4-hydroxychalcone (4HCH), a chalcone derivative, against human coronavirus HCoV-OC43. We found that 4HCH significantly inhibited the cytopathic effect, reduced viral protein and RNA levels in infected cells, and increased the survival rate of HCoV-OC43-infected suckling mice. Mechanistically, 4HCH targets the early stages of viral infection by binding to the epidermal growth factor receptor (EGFR) and inhibiting the EGFR/AKT/ERK1/2 signaling pathway, thereby suppressing viral replication. Additionally, 4HCH significantly reduced the production of pro-inflammatory cytokines and chemokines in both HCoV-OC43-infected RD cells and a suckling mouse model. Our findings demonstrate that 4HCH exhibits potent antiviral activity both in vitro and in vivo, suggesting its potential as a therapeutic agent against human coronaviruses. This study highlights EGFR as a promising host target for antiviral drug development and positions 4HCH as a candidate for further investigation in the treatment of coronavirus infections. Full article

Despite the fact that organochlorine pesticides (OCPs) were banned many years ago, their residues are still present in the natural environment and pose a potential health risk to humans and animals. This study was undertaken to evaluate the effect of meat and bone meal (1.0, 2.0 and 3.0 t ha⁻¹ MBM) derived from animal by-products and used as fertilizer on the content of γ-HCH (γ-hexachlorocyclohexane), DDT (1,1,1-Trichloro-bis-2,2 [4-chlorophenyl]-ethane) and its metabolites (DDD, dichlorodiphenyldichloroethane and DDE, dichlorodiphenyldichloroethylene) in MBM, soil, and maize grain. A long-term small-area field experiment with MBM applied to maize grown in monoculture was conducted at the Agricultural Experiment Station in Tomaszkowo, Poland (53°71′ N, 20°43′ E) from 2014 to 2017. The concentration of γ-HCH in soil decreased gradually, whereas the levels of DDT and its metabolites continued to increase in successive years of the experiment. A minor increase in DDT accumulation in maize grain was also observed, particularly in treatments supplied with mineral fertilizers. Meat and bone meal affected grain contamination levels, and the highest MBM rates decreased the content of DDT metabolites in grain. The results of the study suggest that MBM could be a secondary source of OCPs in the agricultural environment and that their availability to plants varies depending on soil parameters and weather conditions. Full article

The heat transfer enhancement of diamond-shaped ribs mounted in the periodic merging chambers of microchannel (MC) heat sinks is investigated using a numerical method for Reynolds number in the region of 300–700. Compared to triangular, rectangular, and cylindrical ribs, diamond-shaped ribs achieve 3.59%, 13.24%, and 6.34% higher enhancement effects, respectively, under the same mass flow rate. Further analysis of geometric parameters (length, width, and height) and rib positioning reveals that a rib height of h/H_ch = 0.8 provides optimal heat dissipation performance. For Re < 500, the optimal configuration is a rib length of l/L_merg = 0.55 and a width of b/W_ch = 0.8, while for 500 < Re < 700, it shifts to l/L_merg = 0.36 and b/W_ch = 1.6. For s/L_merg, the smaller it is, the shorter the main flow separation time, thereby improving heat transfer efficiency. Full article

Previous studies have examined the association between family dysfunction and pubertal timing in adolescent girls. However, the evidence is lacking on the role of family dysfunction during sensitive developmental periods in both boys and girls from racial and ethnic minority groups. This study aimed to determine the effect of family dysfunction on the timing of pubertal maturation among US Hispanic/Latino children and adolescents. Participants were 1466 youths (50% female; ages 8–16 years) from the Hispanic Community Children’s Health Study/Study of Latino Youth (SOL Youth). Pubertal maturation was measured using self-administered Pubertal Development Scale (PDS) items for boys and girls. Family dysfunction included measures of single-parent family structure, unhealthy family functioning, low parental closeness, and neglectful parenting style. We used multivariable ordinal logistic and linear regression analyses to examine the associations between family dysfunction and pubertal maturation (individual and cumulative measures), with adjustment for childhood BMI and socioeconomic factors, design effects (strata and clustering), and sample weights. Multivariable models of individual PDS items showed that family dysfunction was negatively associated with growth in height (OR = 0.66, 95% CI: 0.44, 0.99) in girls; no associations were found in boys. In the assessment of cumulative PDS scores, family dysfunction was associated with a lower average pubertal maturation score (b = −0.63, 95% CI: −1.21, −0.05) in boys, while no associations were found in girls. Pubertal timing lies at the intersection of associations between childhood adversity and adult health and warrants further investigation to understand the factors affecting timing and differences across sex and sociocultural background. Full article

Effective thermal management in polymer-based materials remains a critical challenge due to their inherently low thermal conductivity, driving the need for advanced nanocomposites. This study develops non-equilibrium molecular dynamics (NEMD) simulations to investigate the thermal transport properties of polyethylene (PE) reinforced with graphene functionalized by hydrogen (H), methyl (CH₃), and ethyl (C₂H₅) groups with volume fractions of 5–30%. The interfacial thermal conductance (ITC) between PE and graphene increases significantly with functionalization, reaching 2.50 × 10⁸ W/m²K with 30% ethyl coverage, a 250% enhancement compared to 8.8 × 10⁷ W/m²K for pristine graphene. The effective thermal conductivity of the PE/functionalized graphene composite peaks at 0.42 W/mK with 30% hydrogen coverage, a 17.4% improvement over the 0.36 W/mK of PE/pristine graphene, though still 6.5% below pure PE (0.45 W/mK). Analysis of the vibrational density of states reveals that ethyl groups maximize phonon coupling at the interface, explaining their superior ITC enhancement. These findings offer quantitative insights into optimizing polymer nanocomposites for thermal management applications, such as microelectronics and energy storage systems, where efficient heat dissipation is important. Full article

To explore how organochlorine pesticides (OCPs) are perpetual in soils and the risk they may bring, Ningbo, a city with an extensive usage history of OCPs, was selected as a case to investigate. Sixty-nine agriculture soils were taken from 0–20 cm layers, then OCPs were analyzed, and a risk assessment was performed. Results indicate five OCPs were detected in agricultural soils, with total concentrations ranging from below detection limits to 43.08 µg·kg⁻¹ and an average value of 15.58 µg·kg⁻¹. Among them, δ-Hexachlorocyclohexane (δ-HCH) and p, p’-Dichlorodiphenyltrichloroethane (p, p’-DDT) were the primary contributors to the residual contamination levels. The health risk assessment indicates that even at maximum exposure levels, the non-carcinogenic risk (1.71 × 10⁻⁴) and carcinogenic risk (5.97 × 10⁻⁸) of OCPs in the study area are significantly below the risk thresholds of 1 and 10⁻⁶, respectively. Monte Carlo simulation further confirms that the 95th percentile values for non-carcinogenic and carcinogenic risks (3.39 × 10⁻⁴ and 1.23 × 10⁻⁷) remain well below these limits, suggesting that the health risks posed by OCPs to adults are negligible. Subsequent ecological risk assessment revealed that the vast majority (73.91%) of soil samples exhibited medium-low ecological risk, with dichlorodiphenyltrichloroethane (DDTs) being the primary contributor to ecological risk. Our findings strengthen the view that although OCPs have been banned for a long time, the ecological risks of residuals in the soil remain a concern, and more effective control methods should be used to mitigate them. Full article

Among the various strategies used to enhance the solvation power of supercritical carbon dioxide (scCO₂), the use of CO₂-philic compounds has been extensively studied over the recent two decades. Given the biocompatibility of this medium, extraction technologies based on scCO₂ are particularly attractive, and a molecular-level understanding of intermolecular interactions is crucial for optimizing processing conditions. Functionalized sugars and cyclic oligosaccharides, such as cyclodextrins, can be rendered soluble in scCO₂, opening new avenues for vectorization strategies and supramolecular chemistry in this medium. To support the exploration of CO₂-philic compounds relevant to these research goals, we conducted a molecular dynamics investigation into the solvation properties of cyclodextrins functionalized with CO₂-philic groups. We thoroughly analyzed the key solute–solvent interactions and their influence on the cavity shape. Additionally, we provided insights into the solvation behavior of peracetylated $\alpha$ and $\beta$-glucose across different regions of the carbon dioxide phase diagram. We were able to confirm the importance of the well-known (acetyl)C–O⋯C(CO₂) interaction, as the most important signature of CO₂-philicity of carbonyl compounds. Depending on the substituent, this interaction can be assisted by a cooperative (methyl)₂HCH⋯O(CO₂) intermolecular bond. In cyclodextrins, conformational flexibility, with a possible change in the conformation of some pyranose units, was observed in the macromolecular structure. On the other hand, these structural modifications were not present for $\alpha$- and $\beta$-glucose. Full article

Common carp (Cyprinus carpio) is extensively cultured and widely consumed in Heilongjiang Province, China. Due to the proximity of freshwater ponds to agricultural cultivated areas, these aquatic systems are inevitably influenced by the historical application of organochlorine pesticides (OCPs), due to their prolonged half-life and resistance to degradation. Gas chromatography-tandem mass spectrometry (GC-MS/MS) was utilized to quantify the levels of hexachlorocyclohexane (HCHs) and dichlorodiphenyltrichloroethane (DDTs) in the muscle tissue of cultured common carp. This study examined the enrichment characteristics of HCHs and DDTs in fish muscle, as well as their correlation with sediment and associated risk assessments. The results showed that the residual levels of HCHs and DDTs in fish muscle ranged from 0.387 μg·kg⁻¹ to 3.418 μg·kg⁻¹ and from 0.114 μg·kg⁻¹ to 0.420 μg·kg⁻¹, respectively. They were all below the maximum residue limits specified in GB 2763-2021 (HCHs: 100 μg·kg⁻¹, DDTs: 500 μg·kg⁻¹). The concentrations of HCHs and DDTs in sediment were found to be lower than those in muscle tissue. Notably, the concentrations of HCHs were higher than those of DDTs in both muscle and sediment. Among the HCHs, γ-HCH was the predominant residual substance, contributing a significant proportion of 42.16% to 86.47%. No significant residues of DDT derivatives were detected. A significant correlation was observed between the concentrations of HCHs and DDTs in the muscle tissue and those present in the sediment (p < 0.01). The health risk assessment indicated that both the carcinogenic and non-carcinogenic risks associated with OCPs from common carp muscle and sediment were within acceptable limits. Therefore, it was recommended to regulate fish consumption during the breeding period. Full article