Search Results (7,899)

To address oil-film electrical breakdown in sliding bearings during operation, an electro-thermal coupled transient model that takes into account the electric field, oil film characteristics, heat conduction, and continuous damage was developed in this paper. The coupled effects of applied voltage U, initial oil-film temperature T₀, and oil-film thickness h on the current density, heat generation rate, and temperature are investigated in the spatial film field and at the characteristic points. The transformation of the oil film from an insulating state to a highly conductive state is revealed. The influencing parameters and rules for the oil-film breakdown time t_b and the characteristic point damage time t_c are also obtained. The results show that increasing the applied voltage or decreasing the equivalent local oil-film thickness shortens the overall breakdown time t_b, while increasing the current density and heat generation rate. In contrast, the initial oil-film temperature primarily affects the overall breakdown time t_b. During oil-film breakdown, two distinct transition points, t_c and t_b, appear in the responses at the characteristic points. At these transition points, the current density and heat generation rate exhibit pronounced transient changes, whereas the oil-film temperature either remains stable or continues to increase. Full article

Background: Alcoholic liver disease (ALD) refers to a progressive liver injury syndrome induced by chronic excessive alcohol intake. Current treatment options are mainly limited to symptom management, and there are safety risks associated with long-term use. Hence, there is an urgent demand to discover new therapeutic targets and investigate natural active substances. Isorhamnetin (IS) is an O-methylated flavonoid, and its specific structure confers unique biological activities and relatively good oral bioavailability, making it a potential natural candidate for the prevention of metabolic liver diseases. However, few studies have explored the application and action mechanism of IS in the intervention of alcoholic liver injury and intestinal flora imbalance. Methods: This work established a mouse model of chronic alcoholic liver injury to evaluate the beneficial effects of IS on hepatic injury, oxidative stress, and intestinal flora disturbance. Results: The results showed that IS intervention therapy can alleviate the symptoms of increased liver index, ALT, AST, TC, and TG levels due to alcohol intake. Furthermore, IS can alleviate liver oxidative stress caused by alcohol consumption, thereby protecting the liver of mice. Intestinal analysis in mice revealed that IS elevated the expression of tight junction proteins ZO-1 and Claudin-1, thereby attenuating alcohol-induced intestinal hyperpermeability and LPS translocation. This further suppressed the activation of the hepatic LPS/TLR4 signaling pathway and decreased the production of TNF-α and IL-1β. Meanwhile, IS significantly improved the intestinal flora disorder induced by alcohol in a dose-dependent manner. Compared with the EtOH group, IS treatment, particularly at the high dose (EISH), significantly increased the Ace, Chao1, Shannon, and Simpson indices. Conclusions: Consistently, NMDS analysis based on the OTU level showed that the IS-treated groups clustered away from the EtOH group and shifted toward the Control group, indicating a partial restoration of the overall microbial community structure toward that of healthy controls. In terms of species composition, IS treatment enriched beneficial microbial communities and inhibited the proliferation of pathogenic bacteria, efficiently restoring intestinal flora homeostasis. Collectively, these findings suggested that the hepatoprotective effects of IS were closely associated with the amelioration of gut microbiota dysbiosis and intestinal barrier function, pointing to a potential involvement of the gut–liver axis, although its causal contribution remains to be confirmed by further mechanistic studies (e.g., microbiota depletion or fecal microbiota transplantation). The findings not only provide new scientific evidence for the hepatoprotective effects of isorhamnetin but also offer a preliminary theoretical basis for the development of natural products potentially targeting the gut–liver axis. Full article

Background: This study aimed to characterize the one-year longitudinal evolution of macrovascular and microvascular parameters following endovascular revascularization in patients with ischemic or neuroischemic diabetic foot ulcers (DFUs). Associations between early post-revascularization vascular parameters and wound-healing outcomes were evaluated as secondary exploratory analyses. Methods: A prospective multicenter longitudinal study included 27 ischemic or neuroischemic DFUs undergoing endovascular revascularization. Patients were followed for 12 months with serial assessments of ankle systolic pressure (AP), toe systolic pressure (TP), ankle-brachial pressure index (ABPI), toe-brachial pressure index (TBPI), transcutaneous oxygen pressure (TcPO₂), and skin perfusion pressure (SPP). Secondary exploratory analyses evaluated associations between early vascular parameters and wound-healing outcomes. Results: Twenty-six ulcers (96.3%) achieved complete healing, with no major amputations or deaths during follow-up. AP, TP, ABPI, and TBPI improved significantly over 12 months (all p < 0.001), whereas TcPO₂ showed a significant overall longitudinal effect (p = 0.010) despite greater variability, and SPP remained unchanged (p = 0.177). Exploratory secondary analyses suggested that higher AP at four weeks after revascularization was associated with shorter healing time (ρ = −0.451, p = 0.024), while higher TcPO₂ values were observed in ulcers with early wound healing (p = 0.040). Conclusions: Macrovascular and microvascular parameters exhibit distinct recovery patterns following endovascular revascularization. Longitudinal assessment of both vascular compartments may provide complementary information for monitoring vascular recovery. The exploratory associations observed between early vascular parameters and wound-healing outcomes warrant confirmation in larger adequately powered studies. Full article

Background: This study evaluated the ecotoxicity of five synergistic antimicrobial combinations of terpineol-antibiotic (SACTA), developed to reduce antibiotic (ABX) doses while maintaining antimicrobial efficacy. The ABXs tested were gentamicin (GTM), chloramphenicol (CHL), tetracycline (TC), and florfenicol (FF). Methods: Median effective concentrations (EC₅₀) were determined using Aliivibrio fischeri and Daphnia magna. In addition, the effects of SACTAs on the metabolic profile of an indigenous riverine microbial community were assessed using Biolog EcoPlates™. Results: α-Terpineol (TER) alone showed EC₅₀ values of 21.49 and 17.64 µg/mL for D. magna and A. fischeri, respectively. The toxicity of SACTAs varied depending on the antimicrobial combination, exhibiting synergistic, additive, or antagonistic effects. Among the tested combinations, TER-CHL was the most toxic with EC₅₀ values of 7.84 µg/mL for D. magna and 12.75 µg/mL for A. fischeri. In contrast, TER-FF and TER-GTM, with lower TER proportions, were the least toxic, with EC₅₀ values exceeding 30 µg/mL for D. magna and 60 µg/mL for A. fischeri. Although SACTAs generally showed higher toxicity than ABXs tested individually, their EC₅₀ values remained below the minimum inhibitory concentrations (MICs) determined in single-species antimicrobial assays. In contrast, riverine microbial communities displayed greater resilience, with only additive or antagonistic effects observed. Among the tested combinations, TER-FF produced the strongest effects on the microbial community, reducing metabolic fitness and decreasing the utilization of carbohydrates and polymers. Importantly, all SACTAs exhibited toxicity values equal to or lower than those of ABXs tested alone at their respective MICs, based on changes in community growth and metabolic profiles. Conclusions: Overall, these findings suggest that SACTAs may represent a promising strategy for reducing ABX use while minimizing additional ecotoxicological risks to freshwater ecosystems. Full article

Reliable in situ observations of sea surface wind (SSW) in tropical cyclones (TCs) remain extremely limited because of the difficulty of operating conventional observing platforms under severe weather conditions. Autonomous, uncrewed surface vehicles (USVs), such as Wave Gliders (WGs), offer a promising solution, but their observational reliability under TC conditions has not been systematically assessed. This study presents a comprehensive evaluation of WG-derived SSW measurements in TCs using (1) internal quality assessment, (2) inter-sensor consistency analysis, and (3) comparisons with satellite observations (AMSR2, SMAP, ASCAT, and SAR) and a numerical weather prediction (NWP) model (JMA LFM). Before evaluating inter-sensor consistency, the influence of platform motion on the 10 m height conversion was assessed. The effect of platform motion correction was negligible, with a maximum RMSE of 0.11 m/s for wind speed and only minor changes in wind direction. Comparisons between sensors mounted on different USVs using 10 m-height-normalized winds showed good agreement over the wind-speed ranges sampled during the TC cases, with the most stable agreement observed under moderate-to-high wind conditions. Comparisons with external datasets also showed good consistency, although the statistical robustness varied among products because of differences in the number of available collocations. For samples within 500 km of the TC center, wind speed RMSE ranged from approximately 0.9 to 4.4 m/s among individual satellite products, while the integrated satellite comparison yielded an RMSE value of 2.36 m/s and the LFM comparison yielded an RMSE of 2.35 m/s. An integrated comparison using all available satellite products also showed strong agreement for wind speed, while the LFM exhibited variability comparable to that of the WG observations under TC-approach conditions. However, the number of independent collocations above 25 m/s was limited, precluding a robust assessment under extreme TC wind conditions. These results demonstrate that mid-size USVs can provide consistent and valuable in situ SSW observations over the range of TC conditions evaluated in this study and highlight their potential for evaluating satellite wind products, supporting NWP model improvement, and advancing air–sea interaction studies in extreme weather environments. Full article

This study investigates the effect of reheating on previously deposited layers in material extrusion (MEX) 3D printing, commonly known as Fused Deposition Modeling (FDM), considering the combined effects of deposition sequence (unidirectional and bidirectional) and key process parameters, including printing temperature, printing speed, and layer height. Two temperature measurement methods were used to record changes during printing, and the results from local and global approaches were compared. The temperature of the interface between the first deposited layer and the build platform was measured with thermocouples. The findings show that the reheating effect at the first layer fades with increasing build layer, with no further increase in heating profile after the eighth layer, regardless of the process parameters investigated. The measured minimum temperatures at the investigated location remained above the glass transition temperature, T_g, which is critical for bonding and polymer chain rearrangement to continue taking place. Printing temperature was found to be the strongest observed factor influencing reheating, as it provides the heat for conduction into previous layers. Deposition sequence also played an important role, with bidirectional deposition leading to higher reheating and 25–50% more layers above the crystallization temperature, T_c. Overall, the results confirm that deposited roads undergo cyclic heating, and understanding the influence of process parameters on reheating is important for interpreting bond formation in MEX 3D printing. Full article

(1) Background: Reference-interval flags read a lipid–glucose panel one analyte at a time. We asked whether a routine five-analyte panel supports reproducible, transportable, auditable descriptive grouping of laboratory profiles. (2) Methods: Retrospective analysis of 21,832 laboratory-order records (adults; glucose, total cholesterol, triglycerides, HDL-C, LDL-C; collection dates not exported) from purchasers of a screening panel in Kazakhstan: log transform, robust scaling, PCA, K-means; eight cluster-number criteria; bootstrap recovery with and without pipeline refitting; frozen-classifier transfer to an identifier-disjoint cohort ($n=\mathrm{11,382}$) with de novo re-derivation; a fully specified reference-interval rule layer. No clinical endpoints were available. (3) Results: Four descriptive laboratory-pattern clusters (lower glucose and lipids; higher LDL-C/TC; higher triglycerides, lower HDL-C; marked hyperglycaemia) had bootstrap Jaccard 0.965–0.981 with and without pipeline refitting and were re-derived independently in the validation cohort (ARI 0.82); a five-cluster configuration was not (0.33). Prevalence-shift point estimates were within 5 percentage points (post hoc exploratory benchmark; the C1 interval slightly crossed it). Rule-based reconciliation changed the delivered category of 8.2% of records from their K-means label; flags alone reproduced 77% of reports but 30% of the triglyceride–HDL-C pattern. (4) Conclusions: The panel supports a stable descriptive partition; prognostic and clinical validity remain to be shown. Full article

Multi-laser powder bed fusion (PBF-ML) enables efficient fabrication of large components but introduces spatially heterogeneous thermal histories near inter-laser overlap zones. However, how global thermal-input variables and local thermal-path variations jointly affect defect evolution, microstructure, and mechanical response in geometrically constrained Ti-6.5Al-3.5Mo-1.5Zr-0.3Si (TC11)structures remains unclear. Here, TC11 arch structures were fabricated by varying laser power, scanning speed, overlap-zone position, and interlayer rotation and characterized by tensile testing, optical metallography, Scanning Electron Microscope (SEM), and fractography. Increasing laser power from 170 to 290 W increased Yield Strength (YS) and Ultimate Tensile Strength (UTS) from 955 and 1228 MPa to 1259 and 1463 MPa, respectively, while Elongation (EL) decreased from 14.7% to 3.1%. Increasing the scanning speed from 1050 to 1450 mm/s produced the opposite strength–ductility trend, whereas overlap-zone position had limited influence on strength and 67° interlayer rotation produced moderate improvements. Defect count and area fraction did not always vary synchronously, while semi-quantitative SEM analysis revealed microstructural coarsening with increasing laser power and refinement with increasing scanning speed. These results show that global thermal-input variables primarily govern the overall strength–ductility and microstructural-scale responses, whereas local thermal-path variables mainly regulate spatial defects and microstructural heterogeneity. Full article

Background/Objectives: Chagas disease is endemic to 21 Latin American countries and is a great public health problem. Current chemotherapy remains unsatisfactory; consequently, the need to search for new drugs persists. The aim of this work is to develop a machine learning computational model, which allows the identification of new chemical compounds with potential trypanosomicidal activity. Methods: A large dataset of 584 compounds, obtained from the Drugs for Neglected Diseases initiative, is used to develop the computational model. AlvaDesc v3.0.14 software is used to calculate the molecular descriptors, and Scikit-learn of Python to obtain the random forest. Results: The best random forest model shows accuracy of 82.1% for the training set and near to 79% for the test set, achieving specificity values over 84.9%, and the false alarm rate values were almost under 15% for both sets. As an experiment of virtual lead generation, the present model is finally satisfactorily applied to the virtual evaluation of a series of 1,2-disubstituted nitroindazolin-3-ones obtained a good agreement between the predicted activity and the experimental assays performed. Compounds 1c and 2c stood out as the most active in the series, with half-maximal inhibitory concentration (IC₅₀) values of 71.3 and 40.9 μM, respectively. Mechanistic analyses suggest that the presence of the nitro group may promote the generation of reactive oxygen species through enzymatic redox activation, potentially involving T. cruzi nitroreductases (TcNTRs), leading to oxidative-stress-mediated parasite death. For the most active compounds, the data are consistent with intracellular hydroxyl radical generation through enzymatic redox processes. Conclusions: Even though none of them resulted more active than nifurtimox, the current results constitute a step forward in the search for efficient ways to discover new lead antitrypanosomals. Full article

Background/Objectives: Doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) is used as a switch regimen in treatment-experienced people with HIV (PWH), particularly when simplification, lipid improvement, or avoidance of interaction-prone regimens is needed. We evaluated 48-week virologic effectiveness and laboratory changes after switching to DOR/3TC/TDF in routine care. Methods: This multicenter retrospective study included adults with HIV who switched to fixed-dose DOR/3TC/TDF at seven Italian HIV centers within the Sardinian HIV Network-Sicilian HIV Cohort (SHINe-SHIC) network. The switch visit served as baseline; follow-up data were extracted at 24 and 48 weeks. The primary endpoint was HIV RNA < 50 copies/mL at 48 weeks in an observed analysis. Secondary endpoints were changes in lipid and lipid-derived parameters, renal function, and hepatic laboratory markers. Results: Ninety-eight participants were included; 75 (76.5%) were male, and the median age was 52.4 years. At 48 weeks, 72/81 participants (88.9%) had HIV RNA < 50 copies/mL and 78/81 (96.3%) had HIV RNA < 200 copies/mL. Total cholesterol decreased from 199 to 165 mg/dL (median paired change, −22 mg/dL; p < 0.001), low-density lipoprotein cholesterol from 118 to 106.5 mg/dL (−13.5 mg/dL; p = 0.001), and triglycerides from 112.5 to 94 mg/dL (−10.5 mg/dL; p = 0.021). Non-high-density lipoprotein cholesterol and the total cholesterol/high-density lipoprotein cholesterol ratio improved, whereas high-density lipoprotein cholesterol decreased modestly. Serum creatinine and estimated glomerular filtration rate remained stable. Alanine aminotransferase increased modestly; aspartate aminotransferase and gamma-glutamyl transferase did not significantly change. Conclusions: Switching to DOR/3TC/TDF maintained virologic control, improved lipid and lipid-derived parameters, and was not associated with renal function decline among participants with follow-up data. In selected treatment-experienced PWH, DOR/3TC/TDF may be useful when lipid improvement, simplification, or management of drug-drug interaction concerns are treatment goals. Full article

In this work, a coupled Johnson-Cook (J-C) constitutive and damage modeling framework was established to investigate damage evolution during thread-rolling of TC16 titanium alloy. The J-C constitutive parameters were calibrated through tensile tests under different strain rates and temperatures, while the stress-triaxiality-dependent damage parameters were identified using specimens with different stress states. A finite element model of two-die radial thread rolling for MJ6 × 1 threads was developed using ABAQUS/Explicit. The mechanical response of the model was evaluated by comparing the numerically predicted and experimentally measured fracture displacements, with a maximum relative deviation of 7.63% in fracture displacement. The calibrated framework was subsequently applied to analyze stress distribution, plastic deformation localization, and damage evolution during the thread rolling process. The results indicate that damage accumulation is mainly concentrated at the thread root and the transition region between the thread flank and root. The damage of the thread can be attributed to the combined effects of high equivalent plastic strain, stress concentration, and an unfavorable stress state. The predicted damage localization agrees well with the experimentally observed fracture region under the investigated rolling condition. These findings demonstrate the applicability and limitations of the coupled Johnson-Cook constitutive damage framework for analyzing defect evolution in complex forming processes. Full article

The highly conserved QseB/QseC two-component system (TCS) in Glaesserella parasuis (G. parasuis) regulates gene expression, with QseC as a histidine kinase and QseB as a response regulator. This study employed data-independent acquisition (DIA) quantitative proteomics to investigate the effects of qseB deletion on bacterial morphology, proteome, and molecular regulation. Electron microscopy revealed that the ΔqseB mutant exhibited ultrastructural damage, including cell shrinkage, membrane impairment, cell wall separation, and protoplast dissolution, indicating that the loss of qseB resulted in severe compromise of cellular structural integrity. A total of 1493 proteins were identified by DIA quantitative proteomics. Fifty-five proteins were differentially expressed between the ΔqseB mutant and the wild-type strain SC1401. Among them, 24 were upregulated and 31 were downregulated. Upregulated proteins were mainly heat shock proteins (DnaK, HslV/U, ClpB), molecular chaperones (GroL, HtpG, HslO), and co-chaperone GroES, along with translation inhibitors RaiA and RsfS. These proteins participate in stress response, protein folding, and proteostasis maintenance. The downregulated proteins included QseC, LolB, CarB, ThiL, and Tgt, which are linked to TCSs, quorum sensing, and transport functions. KEGG analysis indicated that the differentially expressed proteins are involved in RNA degradation, amino acid metabolism, and ABC transporters. Protein–protein interaction (PPI) network analysis identified 10 core hub proteins, including GroEL, HslU, and QseC. These proteins may play key roles in maintaining cellular homeostasis. Integrated multi-omics analysis identified three genes (dnaK, hslU, hslO) that were differentially expressed in both transcriptomic and proteomic data. qRT-PCR results confirmed these findings. In summary, loss of qseB disrupts the QseB/QseC system. This affects stress response, metabolism, and cell structure. These changes may affect bacterial fitness and host adaptation, providing clues for understanding the pathogenic mechanisms of G. parasuis. Full article

Obesity is a prevalent metabolic disorder characterized by excessive lipid accumulation. This study aimed to investigate the anti-obesity effects and underlying mechanisms of two triterpenoid saponin-rich extracts, designated disaccharide saponin-rich extract (DTS) and trisaccharide/tetrasaccharide saponin-rich extract (TTS), prepared from adzuki bean (Vigna angularis). In vitro, both DTS and TTS extracts significantly inhibited lipid accumulation in 3T3-L1 adipocytes without cytotoxicity, with TTS reducing lipid droplets to 21.45% of the model group at 200 μg/mL. In vivo, C57BL/6J mice were fed a high-fat–high-cholesterol diet (HFD) for 12 weeks and orally administrated with DTS or TTS (30, 60, or 120 mg/kg/day) via gavage; the results showed marked reductions in body weight gain (up to 20.37%), fat mass, liver coefficient, and serum levels of total cholesterol (TC), triglyceride (TG), Low-Density Lipoprotein Cholesterol (LDL-C), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST), while elevating high-density lipoprotein cholesterol (HDL-C) levels. Mechanistically, transcriptomics and Western blot analyses revealed that both extracts were associated with upregulation of the PPARα-ACOX1 axis, consistent with enhanced fatty acid β-oxidation, and downregulation of the PPARγ-FABP4 pathway, consistent with reduced adipogenesis, suggesting a dual shift toward lipid catabolism and away from lipid synthesis. Furthermore, 16S rRNA sequencing demonstrated that both saponin extracts reversed HFD-induced gut dysbiosis by restoring α-diversity and orchestrating distinct genus-level modulations, specifically suppressing obesity-associated pathobionts (Faecalibaculum and Ileibacterium) while concurrently enriching beneficial commensals (Bifidobacterium). Notably, TTS at 120 mg/kg reduced body weight gain to a greater extent than the positive control orlistat (p < 0.05, Tukey’s HSD), with comparable improvements in serum lipid profiles and liver function parameters. Collectively, these findings demonstrate that adzuki bean saponin extracts exert anti-obesity effects in HFD-fed mice and are associated with multi-target changes involving the “liver–adipose–gut axis,” supporting their further evaluation as candidate as functional food ingredients for metabolic health. Full article

Microplastics are an increasingly pervasive contaminant of agricultural soils, where they frequently co-occur with heavy metals such as nickel (Ni), an element still catalogued mainly as a pollutant yet now recognised as an essential plant micronutrient and the cofactor of urease. A pot experiment assessed how three of the most common microplastics—polyethylene (PE), poly(ethylene terephthalate) (PET) and polystyrene (PS), added at 2% v/v—affect nickel behaviour in two calcareous agricultural soils differing chiefly in texture (Soil 1, a clay loam; Soil 2, a silty clay), cropped with industrial hemp (Cannabis sativa L., cv. Fedora 17) and tobacco (Nicotiana tabacum L., cv. Burley). Forty-eight pots (2 soils × 4 treatments × 2 crops × 3 replicates) were analysed for pseudo-total (aqua regia), bioavailable (DTPA-extractable) and plant-tissue Ni. Pseudo-total Ni was unchanged across all treatments (15.1–15.4 mg kg⁻¹), confirming that microplastics are modifiers and not sources of the metal. DTPA-extractable Ni rose significantly under PE and PS in the coarser-textured Soil 1 (1.87 and 1.80 versus 1.69 mg kg⁻¹) but not in the finer-textured Soil 2. Tissue Ni nevertheless declined under every polymer, in the order control > PE > PS > PET, and was consistently lower on Soil 2. The Bioavailability Factor and the soil-referenced transfer indices (BAF, TC) followed the same pattern, whereas the internal root-to-shoot Transfer Factor remained close to unity, indicating that microplastics restrict the acquisition of nickel rather than its internal distribution. Neither crop showed visible symptoms of phytotoxicity and both completed their full growth cycle; because biomass was not quantified, no conclusion regarding yield is drawn. Chemically measured availability therefore ceases to predict plant uptake under microplastic amendment, with implications both for the expected efficiency of Ni phytoextraction and for the supply of an essential micronutrient on calcareous soils. Full article

Tetracycline (TC)–copper (Cu) co-contamination can impair soil functioning and intensify selection for antibiotic resistance. In a 49-day microcosm experiment, we evaluated the effects of Chlorella pyrenoidosa supplementation on soils treated with TC (0, 30, or 100 mg·kg⁻¹) and Cu (0, 100, or 500 mg·kg⁻¹). TC removal, extractable Cu, soil physicochemical properties, enzyme activities, tetracycline resistance genes (TRGs), and microbial community composition were assessed. In unamended contaminated microcosms, TC dissipation ranged from 22.7% to 43.5%, whereas C. pyrenoidosa amendment increased TC dissipation to 49.9–73.5%. The addition also reduced extractable Cu by 35.6–50.6%, partially restored dehydrogenase and catalase activities, and altered bacterial community structure. Metagenomic analysis showed that tetX was the predominant TRG detected and that algal supplementation was associated with lower total TRG signals and reduced relative abundances of several pollution-associated taxa, including Rhodanobacter. Correlation analyses revealed associations among TRGs, microbial taxa, and treatment conditions but did not establish direct host–gene relationships or horizontal gene transfer. Overall, C. pyrenoidosa application enhanced TC removal and Cu immobilization and was associated with reduced enrichment of the tetracycline resistome. Full article