Search Results (35,303)

The high pressure response and structural stability of crystalline racemic (RS) ibuprofen up to 7 GPa are explored by Raman spectroscopy, employing diamond anvil cells for the pressure application and glycerol as the pressure transmitting medium. Two independent high pressure experiments were performed with practically identical results. Both intermolecular vibrations (associated with weak van der Waals interactions and hydrogen bonding between ibuprofen molecules) and intramolecular vibrations (associated with strong covalent bonding within the ibuprofen molecule) are monitored as a function of pressure, with the former being far more susceptible to volume contraction. The pressure dependence of the Raman peak frequencies undergoes two distinct changes at ~2 and ~6 GPa, indicating the occurrence of pressure-induced structural modifications of ibuprofen. Based on the high pressure Raman data for the intermolecular vibrations of the RS ibuprofen below 2 GPa, a zero pressure value for the bulk modulus of ~7.5 GPa is also extracted. Full article

In industrial quality control, the precise identification of severe structural weld defects is paramount. Traditional 2D image-based detection methods are susceptible to illumination and texture interference, while high-precision 3D laser scanning solutions are costly and impractical for large-scale deployment. To achieve reliable geometric defect detection at low cost, this paper proposes a detection framework based on monocular depth estimation and a dual-attention point cloud network. First, YOLOv8 is employed for rapid region of interest extraction, and an advanced monocular depth estimation model generates 3D pseudo-point clouds containing geometric information. Secondly, addressing the challenge of distinct spatial orientation features in missed weld defects that are prone to confusion, this paper introduces a dual-attention-enhanced point cloud classification network named DA-PointNet++. This model embeds dual-attention modules within the PointNet++ backbone network, enhancing key feature representation in both the channel and spatial dimensions. Experimental results demonstrate that this approach achieves an accuracy of 93.67% and a recall rate of 90.51% in a unified binary classification task for general weld defect detection, effectively identifying both normal welds and complex missed weld defects. Compared to PointConv, Dynamic Graph Convolutional Neural Network (DGCNN), and mainstream Point Cloud Transformer, this method significantly reduces false negative rates while maintaining low computational costs, offering a cost-effective solution for industrial automation. Full article

The entomopathogenic fungus Beauveria bassiana (Hypocreales: Cordycipitaceae) is widely used as a biological control agent, yet its efficacy against orthopteran pests remains poorly characterized. In this study, we evaluated the susceptibility of second-, third-, and fourth-instar nymphs of the Italian locust, Calliptamus italics (Orthoptera: Acrididae), to B. bassiana strain PPRI5339 under controlled laboratory conditions. Nymphs were exposed to six conidial concentrations (1 × 10³ to 1 × 10⁸ conidia/mL) via treated food, with mortality recorded over 10 days. The fungus caused significant, dose- and time-dependent mortality across all instars. Second-instar nymphs exhibited the highest susceptibility, with an LC₅₀ of 5.8 × 10⁵ conidia/mL and an LT₅₀ of 3.1 days at the highest concentration. Susceptibility decreased with advancing developmental stage; fourth-instar nymphs required higher concentrations and longer exposure to achieve comparable mortality (LC₅₀ = 2.3 × 10⁶ conidia/mL; LT₅₀ = 4.5 days). Cox proportional hazards analysis confirmed that the mortality hazard was significantly lower for third (HR = 0.66) and fourth (HR = 0.51) instars compared to second instars (HR = 1.00). These results demonstrate that B. bassiana is pathogenic to C. italicus, with pronounced stage-dependent susceptibility. Full article

Ti-6Al-4V ELI (Grade 23) fabricated by Laser Powder Bed Fusion (LPBF) exhibits well-known susceptibility to adhesive wear and tribo-oxidation under dry sliding, yet the tribological consequences of in-process laser remelting remain poorly characterized. This study investigates the influence of an in-layer laser scan strategy (single-scan and double-scan), normal forces in the 5–15 N range, and a sliding speed of 0.10–0.20 m·s⁻¹ on the dry sliding tribological response of additive manufactured Ti-6Al-4V ELI. A full factorial experimental design was carried out and the most significant factors and their contributions to the coefficient of friction, specific wear rate, and contact temperature were identified by a statistical method using a general linear model (GLM). The optimal parameters for both of the scan strategies were predicted using a response surface methodology (RSM). Furthermore, to assess the effect of the laser scan strategy and the in-layer remelting on the local mechanical properties, a microscale and nanoscale indentation was carried out. The results show that the normal load was the dominant factor with a contribution of 89.3% for the coefficient of friction, 54% for the specific wear rate, and 40.5% for the temperature. A significant load–scan strategy interaction that governed the wear behavior was detected. The double-scan strategy exhibited higher wear at 5 N but lower wear at 15 N than the single-scan, a counter-intuitive reversal attributed to the load-threshold tribolayer stabilization promoted by the remelting-induced near-surface microstructural modification. The novelty of this study was the setup of a robust GLM–RSM framework for predictive modeling and optimization of additively manufactured surfaces under tribological loading. Full article

Background: Late-onset neonatal sepsis (LONS) remains a major cause of morbidity in preterm neonates admitted to the neonatal intensive care unit (NICU), yet the contribution of vitamin D status to neonatal infectious susceptibility remains uncertain. Objective: To evaluate clinical and demographic variables and serum vitamin D levels assessed at birth in preterm neonates with and without LONS. Methods: A retrospective observational cohort study was conducted in a tertiary NICU in northeastern Mexico between May 2023 and October 2024. Preterm neonates (<37 weeks of gestation) with serum 25(OH)D measured within the first hour of life were included. Vitamin D status was classified as sufficient (≥30 ng/mL), insufficient (20–29 ng/mL), or deficient (<20 ng/mL). LONS was defined as sepsis occurring after 72 h of life. Comparisons between neonates with and without LONS were performed using Fisher’s exact test for categorical variables and Student’s t-test or Mann–Whitney U test for continuous variables, as appropriate. Results: Twenty-nine preterm neonates were included (mean gestational age: 32.0 ± 2.6 weeks; mean birth weight: 1748 ± 545 g). The mean serum 25(OH)D level at birth was 35.5 ± 13.0 ng/mL. LONS occurred in 31% (9/29) of neonates, of which 55% were microbiologically confirmed. No significant differences were observed in vitamin D levels between neonates with and without LONS (35.0 ± 12.0 vs. 35.7 ± 13.7 ng/mL; p = 0.899). Vitamin D deficiency was not associated with LONS (OR 1.13, 95% CI 0.09–14.28). The prevalence of vitamin D deficiency was low (10%) in this cohort. Conclusions: A clear association between serum 25(OH)D levels at birth and the development of LONS could not be demonstrated in this small exploratory cohort. Given the limited sample size and low prevalence of vitamin D deficiency, further multicenter prospective studies are required to better understand the potential relationship between vitamin D status and neonatal infectious outcomes. Full article

Foot-and-mouth disease (FMD) is a highly transmissible viral infection of livestock that threatens food security and causes substantial economic losses in endemic regions. Despite its economic impact, the role of environmental viral load and wildlife reservoirs in sustaining FMD transmission remains poorly quantified. The aim of this study is to assess the extent to which community viral load sustains FMD persistence and to identify key transmission drivers in a coupled livestock–wildlife–environment system. A Susceptible–Exposed–Infected (SEI) model with a free-living virus compartment was analyzed via the basic reproduction number ($R_0$) and solved numerically using a Nonstandard Finite Difference Method. Sensitivity analysis identified wild host population size, transmission rates, host recruitment, environmental viral decay, and viral load thresholds as major determinants of $R_0$. Results indicate that higher transmission rates accelerate susceptible depletion and increase exposed and infected classes, with wildlife dominating environmental viral contributions. Community viral load is central to sustaining outbreaks and informs targeted control strategies. Full article

Continuous streamflow monitoring is fundamental for water management in high-mountain Andean basins. Traditionally, this process relies on empirical regressions, although artificial intelligence (AI) has recently emerged as a robust alternative. However, extreme geomorphological dynamics compromise classical hydraulic methods, while AI models frequently lack physical validation. In this context, this study compares the performance of Artificial Neural Networks against traditional methods to reduce uncertainty in stage–discharge rating curves. The methodology, applied to a nested basin scheme in Loja, Ecuador, contrasted traditional exponential fits with a Multilayer Perceptron optimized using the Levenberg–Marquardt algorithm. The analysis included the evaluation of uncertainty bands and a sub-hourly spatial validation based on the principle of mass conservation. Results evidence that AI refines statistical accuracy (NSE > 0.95) and effectively adapts to bed non-linearity; nevertheless, cross-validation revealed a high susceptibility to algorithmic overfitting. It is concluded that while AI offers superior analytical flexibility for interpolating non-linear dynamics, traditional methods remain more robust for extreme flood extrapolation. Furthermore, while AI reduces computational complexity, it entails a higher “data cost” requiring denser field gauging campaigns. Operational viability requires rigorous dynamic uncertainty controls and spatial water balance validation. Full article

Background: Acinetobacter baumannii (A. baumannii) is a critical-priority pathogen of major concern in healthcare settings. Colistin remains a last-resort antibiotic for multidrug-resistant (MDR) A. baumannii infections; however, resistance is increasingly reported worldwide yet remains understudied in Bahrain. Reliable detection methods and understanding clonal dissemination are essential for infection control. Objectives: This study aimed to (1) determine the rate of colistin resistance in 102 clinical A. baumannii isolates from Bahrain, (2) evaluate the diagnostic performance of the colistin agar test (CAT) and E-test against broth microdilution (BMD method), and (3) assess clonal relationships using BOX-PCR fingerprinting. Methods: 102 clinical isolates from multiple hospitals in Bahrain underwent susceptibility testing via the BMD method, CAT, and E-test; screening for mcr-1 to mcr-5 genes; and BOX-PCR DNA fingerprinting. Results: Colistin resistance was detected in 14.7% of isolates by BMD method, higher than regional and global averages. All resistant isolates were mcr-negative, suggesting chromosomally mediated resistance. CAT showed 86.7% sensitivity, 98.8% specificity, and a 13.3% very major error rate. The E-test failed to detect resistant isolates (very major error 100%). BOX-PCR revealed predominant clonal relatedness with intra- and inter-hospital spread. Conclusions: Colistin resistance in A. baumannii from Bahrain exceeds regional and global levels, likely driven by chromosomal mechanisms under selective pressure. The BMD method remains the gold standard for colistin testing, while CAT may serve as a screening tool requiring confirmation. Strengthened stewardship and infection control measures are vital to contain dissemination. Full article

Verticillium wilt (VW), caused by the soil-borne phytopathogen Verticillium dahliae, is a devastating vascular disease that severely threatens global cotton production and causes substantial economic losses. Jasmonic acid (JA) signaling plays a crucial role in plant innate immunity; however, the molecular mechanisms governing JA biosynthesis during cotton defense responses to V. dahliae infection remain largely elusive. In this study, we identified that GhAOS1 (allene oxide synthase 1), a key rate-limiting enzyme-encoding gene in the JA biosynthetic pathway, was rapidly and significantly induced by V. dahliae infection and exclusively localized in chloroplasts. Functional analysis in GhAOS1-silenced cotton and overexpressing Arabidopsis plants demonstrated that GhAOS1 positively regulates resistance to V. dahliae. Transcriptome analysis of GhAOS1-silenced cotton plants showed that DEGs are significantly enriched in phenylpropanoid biosynthesis, flavonoid biosynthesis, and α-linolenic acid metabolism pathways. Consistent with these findings, silencing GhAOS1 significantly reduced endogenous JA levels and suppressed the expression of defense-related genes and JA biosynthetic genes in cotton. Furthermore, we identified that the transcription factor GhWRKY70 directly binds to the W-box cis-acting element in the GhAOS1 promoter through Y1H, LUC, and EMSA, which activated GhAOS1 transcription. Silencing GhWRKY70 in cotton significantly enhanced plant susceptibility to V. dahliae and suppressed the expression of JA signaling pathway-related genes. Collectively, our results elucidate that GhWRKY70 positively regulates cotton resistance to VW by activating GhAOS1-mediated JA biosynthesis, revealing a novel GhWRKY70-GhAOS1 regulatory module that integrates JA signaling to coordinate cotton immune responses against V. dahliae. This study provides new insights into the molecular mechanism of JA-mediated defense and offers potential targets for molecular breeding of VW-resistant cotton. Full article

Severe asthma (SA) is a chronic respiratory disease characterized by clinical heterogeneity and poor therapeutic response. Variants in the IL4 gene, including rs2243250 and rs2243248, have been associated with asthma susceptibility and severity in different populations; however, their role in the Mexican population remains unclear. This study evaluated the association of IL4 promoter variants rs2243250 and rs2243248 with SA and related clinical characteristics in a Mexican population using genetic and in silico approaches. In total, 106 patients with SA and 180 healthy individuals were included. Genotyping was performed using allelic discrimination assays with TaqMan^® probes, and associations between genotypes and clinical variables were assessed. No significant differences in allele or genotype frequencies were observed between groups. However, the rs2243250 TT genotype was associated with nocturnal symptoms (OR = 3.03, 95% CI = 1.31–7.00, p = 0.009) and increased use of rescue medication (OR = 3.16, 95% CI = 1.41–7.07, p = 0.005). The rs2243248 TG/GG genotypes were associated with epithelial allergy (p < 0.05). In silico analysis suggested a regulatory role for both variants. These findings suggest that IL4 variants may not influence overall disease risk but could modulate clinical features of asthma severity. Full article

Colorectal cancer (CRC) and non-Hodgkin lymphoma (NHL) are among the most prevalent cancer types globally by incidence and mortality. Both types are influenced differentially by chronic inflammation. Central to this inflammation are inflammatory genes that are meticulously regulated by nuclear factor kappa B (NF-κB) and tumor necrosis factor-α (TNF-α). NF-κB is negatively regulated by IκBα (encoded by NFKBIA), while TNF-α’s actions can be modulated by ghrelin (encoded by GHRL). We investigated four single nucleotide polymorphisms (SNPs) in NFKB1 (rs4648068), NFKBIA (rs2233406), TNF-α (rs1800629), and GHRL (rs1629816) as biomarkers for CRC and NHL risk in a cohort of Kuwaiti individuals. DNA samples from patients and controls were collected and genotyped for all SNPs, and their association with CRC or NHL risk was assessed. While rs4648068 showed a modest association with increased CRC risk, it had no significant impact on NHL risk. Conversely, rs2233406 increased NHL risk without affecting CRC risk. Interestingly, while rs1800629 showed a protective effect against NHL, it showed an increased risk for CRC. Finally, rs1629816 was associated with greater NHL but not CRC risk. Our findings suggests that variations of these inflammatory genes may be useful indicators for predicting cancer risk but might have unpredictable effects on cancer susceptibility, depending on the cancer type. Full article

Blockchain-based crowdsourcing logistics is a promising decentralized paradigm for solving the “last-mile delivery” problem, in which smart contracts automatically execute the business logic. Since crowdsourcing logistics inherently involves frequent fund transfers, its smart contracts are particularly susceptible to reentrancy vulnerabilities. Existing works address reentrancy by inserting a lock mechanism at design-time, which lacks dynamic responsiveness and incurs additional gas overhead. To overcome this limitation, we propose RE4SC, the first runtime enforcement framework for vulnerable smart contracts. RE4SC contains two components: off-Blockchain granularity segmentation and on-Blockchain granular block reordering. At the off-Blockchain level, bytecode is segmented into granular blocks through control flow analysis. This yields a finer granularity than conventional basic blocks in a control flow graph. These granular blocks are then organized into a tree structure that captures their hierarchical nesting relationships. A data flow analysis further ensures data dependency consistency after reordering. At the on-Blockchain level, a runtime enforcer retrieves the pre-computed reordering specifications from off-Blockchain analysis. It applies a depth-first reordering algorithm to reposition key state variable assignments before transfer operations, eliminating reentrancy vulnerabilities without introducing additional bytecode. We implement a prototype tool and make it open-source. Experiments on self-constructed crowdsourcing logistics contracts and three public datasets demonstrate that RE4SC repairs vulnerable contracts with zero gas overhead, outperforming existing approaches. Full article

Lameness associated with bacterial chondronecrosis with osteomyelitis (BCO) continues to be an important topic of great interest to global poultry production. Caused by bacterial infection of susceptible necrotic bone tissue, the disease severely affects animal health, welfare, and productivity, leading to significant economic losses annually. In recent years, the Kazakhstan poultry industry has enjoyed significant investment and strong growth, with goals of self-sufficiency within the decade. However, there remains a significant knowledge gap in poultry research in the nation, especially regarding the topic of BCO lameness. As such, this study aims to provide a preliminary evaluation of BCO lesion prevalence in different geographical regions of the country―namely Abai, Almaty, and Akmola. In each region, about 200 broilers from local poultry farms were procured, humanely euthanized, and necropsied to evaluate prevalence of femoral and tibial lesions commonly associated with BCO lameness. On average, most broilers had no damage to femoral head (78.17%) followed by femoral head separation (FHS, 11.94%), while the tibial head saw ubiquitous degrees of damage ranging from severe (71.42%) to observable (23.06%). These findings signify potential underlying issues connected to BCO lameness that will necessitate early management and intervention measures to prevent future spread of the disease. Full article

Vitiligo is a chronic, acquired autoimmune disorder characterized by white skin patches resulting from the loss of epidermal melanocytes. Vitiligo may arise through multiple mechanisms, including genetic susceptibility, oxidative stress, autoimmune dysfunction, and environmental factors. Treatment strategies have focused on inhibiting melanocyte loss and stimulating repigmentation. Mitogen-activated protein kinase (MAPK) pathways regulate various cellular processes, including differentiation, survival, and inflammatory responses. The dysregulated MAPK pathways play distinct roles in the development of vitiligo through a complex interplay of melanogenesis, oxidative stress, and autoimmune responses within different cells, thereby leading to melanocyte damage. Thus, therapeutic targeting of MAPK pathways has the potential to mitigate oxidative stress-induced damage and inhibit the exaggerated autoimmunity, thereby controlling disease progression and supporting repigmentation. This review provides an overview of MAPK signaling across the multicellular network in vitiligo pathogenesis and summarizes agents that may provide new perspectives for therapeutic intervention. Full article

Objective: Posaconazole, a second-generation triazole antifungal used for the prevention or treatment of invasive fungal infections, has been shown to markedly increase tacrolimus exposure in vivo when co-administered, potentially leading to clinically significant adverse events. A physiologically based pharmacokinetic (PBPK) model was developed to predict tacrolimus–posaconazole interactions in renal transplant recipients with different CYP3A5 genotypes, to inform tacrolimus dose adjustment in clinical practice. Methods: First, to obtain the critical inhibition parameters, in vitro enzyme kinetic studies were conducted. Based on these data, a whole-body physiologically based pharmacokinetic (PBPK) model for TAC was developed and validated in PK-Sim. A published, validated posaconazole PBPK model was applied concurrently. Model performance was evaluated against published pharmacokinetic data in healthy volunteers receiving tacrolimus with posaconazole. A virtual Chinese renal transplant recipient was generated by incorporating population-specific physiological parameters, including CYP3A5 genotype-dependent enzyme expression. Results: In vitro experimental results demonstrated that POSA acts as a potent reversible competitive inhibitor of CYP3A4/5-mediated TAC metabolism. The tacrolimus PBPK model adequately captured pharmacokinetics across CYP3A5 genotypes, and tacrolimus pharmacokinetics during co-administration with posaconazole were also predicted. Compared with CYP3A5 expressers, nonexpressers showed greater variability in tacrolimus whole-blood concentrations and greater susceptibility to posaconazole-mediated interactions. The CYP3A5*3*3 genotype was associated with higher C_max and AUC. Dose optimization simulations predicted that after 6–7 days of posaconazole co-administration, nonexpressers would require the reduction of tacrolimus dosing frequency from every 12 h to every 24 h to maintain trough concentrations within 8–15 ng/mL, whereas a 50% dose reduction was predicted to be optimal for expressers. Conclusions: A tacrolimus–posaconazole PBPK drug–drug interaction model was developed for the population of renal transplant recipients and used to simulate tacrolimus trough concentrations across CYP3A5 genotypes and dosing regimens, supporting genotype-informed co-administration in clinical practice. Full article