Search Results (10,775)

The mechanism of separating the small chiral drug molecules on large soft polymers is essential in pharmaceutical science. As a case study, the differentiation mechanism of ibuprofen, (R,S)-2-(4-isobutylphenyl)propanoic acid, with cellulose tris(4-methylbenzoate) (CMB) as the chiral stationary phase (CSP) was investigated by combining the molecular docking simulation and multi-level layered terminal-to-center elongation (ML-T2C-ELG) method. Our results demonstrated that, based on the optimized geometry using the ML-T2C-ELG method, the complexation energy of S-ibuprofen with CMB obtained at B3LYP-D3(BJ)/6-311G(d) level is more negative than that of R-ibuprofen, which is caused by the greater hydrogen bonding and π-π stacking interactions between CMB and S-ibuprofen. The results are in line with the experimental observations of high-performance liquid chromatography (HPLC) that the retention time of S-ibuprofen on CMB is longer than that of R-ibuprofen. Moreover, the ML-T2C-ELG method was found to be valuable for optimizing the geometries of such flexible and large systems, which allows for a more accurate description of interactions between soft polymers and small molecules when coupled with the docking simulation. It is anticipated that this study can provide beneficial insights for future optical resolution mechanisms of other chiral drugs. Full article

Background/Objectives: Endovascular treatment has become the primary treatment for intracranial aneurysms, yet direct bypass surgery remains an option in selected cases where standard approaches fail. This study aims to evaluate the role, indications, and outcomes of bypass surgery for intracranial aneurysm management in the current endovascular era. Methods: A single-center retrospective analysis was conducted on consecutive cases who underwent direct intracranial bypass surgery for intracranial aneurysms between 2015 and 2024. Data on demographics, aneurysm characteristics, indications, bypass type, patency, and clinical outcomes (using the modified Rankin Scale) were collected. Results: Of the 101 bypasses performed between 2015 and 2025, 25 were used for complex aneurysm cases. Intracranial bypass was necessary in as many as 5% of all microsurgical aneurysm repairs in 2023 and 10% in 2024. Bypass surgery was indicated in young patients with complex aneurysms not amenable to endovascular therapy (45%) and in 20% of the cases for recanalized aneurysms after previous endovascular repair. Intraoperative and postoperative bypass patency was confirmed for all patients except one case due to ongoing malignant brain swelling after an ongoing infarction. At follow-up, 87% of patients, with both ruptured and unruptured aneurysms, had a good outcome (mRS ≤ 2), and all patients had a patent bypass. Permanent morbidity was observed in 5% and procedure-related mortality in 0%. Conclusions: While bypass surgery constitutes a minority of intracranial aneurysm treatment by volume, its role in intracranial aneurysm repair is crucial and relevant in response to the evolving complexity of aneurysms. Further refinement of techniques is necessary. Full article

Continental ecosystems are crucial constituents of the worldwide carbon process, and their carbon source and sink processes are highly sensitive to human-induced climate change. However, the spatiotemporal changes and principal determinants of carbon source/sink in Shandong Province remain unclear. This study constructs six dominant control modes of carbon sources/sinks based on three carbon sink indicators (gross primary production (GPP), net primary production (NPP), and net ecosystem productivity (NEP)) and three carbon source indicators (autotrophic respiration (Ra), heterotrophic respiration (Rh), and total ecosystem respiration (Rs)), revealing the main control characteristics of the spatiotemporal dynamics of carbon source/sink in the continental ecosystems of Shandong Province. Additionally, the principal determinants of carbon sources and sinks are quantitatively analyzed using cloud models. The research findings are as follows: (1) From 2001 to 2020, the continental ecosystem of Shandong Province demonstrated a weak carbon sink overall, with both carbon sinks and sources showing fluctuating growth trends (growth rate: GPP, NEP, NPP, Rs, Ra, and Rh consist of 15.55, 6.14, 6.09, 9.59, 9.47, and 0.07 gCm⁻²a⁻¹). (2) The dominant control characteristics of carbon source/sink in Shandong Province exhibit significant spatial differentiation, which can be classified into absolute carbon sink cities (Jinan, Zibo, Rizhao, Jining, Liaocheng, Zaozhuang, Binzhou, Dezhou, Tai’an) and relative carbon source cities (Weifang, Yantai, Weihai, Linyi, Qingdao, Heze, and Dongying). GPP is the dominant control factor in carbon sink areas and is widely distributed across the province, while Rs and GPP are the dominant control factors in carbon source fields, focused on the eastern coastal and southwestern inland sites. (3) Landscape modification and rainfall are the main driving elements influencing the carbon sink and source variations in Shandong Province’s continental ecosystems. (4) The spatial differentiation of the driving factors of carbon producers and reservoirs is significant. In absolute carbon sink cities, land-use change and vegetation cover are the dominant factors for carbon sinks and sources, with significant changes in both range and spatial differentiation. In relative carbon source cities, land-use change is the leading factor for carbon source/sink, and the range of changes and spatial differentiation is most notable. The observations from this study supply scientific underpinnings and reference for enhancing carbon sequestration in continental ecosystems, urban ecological safety management, and achieving carbon neutrality goals. Full article

Background/Objectives: Gestational diabetes (GD) is a common pregnancy complication linked to inflammation. Obesity, a major risk factor, is associated with elevated pro-inflammatory markers (TNF-α, IL-6) and reduced anti-inflammatory IL-10 and adiponectin. This study investigated the role of inflammatory factors (IL-6, TNF-α, IL-10, adiponectin) and their genetic variants (rs1800629, rs1800796, rs1800896, rs266729) in a unique four-group study design of pregnant women. Methods: We collected venous blood from 162 women in the third trimester of pregnancy. We measured IL-6, IL-10, TNF-α, and adiponectin levels and performed real-time PCR genotyping for the selected SNPs. Results: IL-6 levels were significantly higher (p < 0.001) in pregnant women with GD and additional complications. The IL-6 SNP rs1800796 heterozygous CG genotype showed a slightly increased GD risk (OR = 1.41). However, we found no significant associations between GD and TNF-α rs1800629 or IL-10 rs1800896 SNPs. The AdipoQ rs266729 homozygous CC genotype was linked to increased GD risk (p = 0.03 for superdominant model). Importantly, no significant correlations were observed between inflammatory marker levels and gene variants within any study group. Conclusions: Our findings suggest a greater inflammatory burden in GD pregnancies with additional complications. While certain IL-6 and AdipoQ variants might contribute to GD risk, the overall weak association between inflammatory markers and gene variants likely reflects the complex polygenic nature of GD, environmental factors, or the study’s sample size. Full article

Background/Objectives: Stroke is a cerebrovascular disorder characterized by vessel occlusion or rupture, resulting in brain damage and subsequent physical impairment. Recent studies have implicated hevin–calcyon protein binding in the repair of brain injury. Secreted protein acidic and rich in cysteine–like 1 (SPARCL1) encodes hevin. This study investigated SPARCL1 gene polymorphisms in ischemic stroke to identify potential biomarkers for brain injury treatment. Methods: we examined the associations of SPARCL1 polymorphisms (rs1049544, rs1130643, rs7695558, rs1049539) with ischemic stroke. This case–control study involved 387 controls and 509 patients with ischemic stroke. Genotyping was performed via real-time polymerase chain reaction with the TaqMan™ SNP Genotyping Kit. Results: The rs1049544 polymorphism was significantly associated with ischemic stroke prevalence (GG vs. CC: adjusted odds ratio [AOR] = 0.642, p = 0.043; GG + GC vs. CC: AOR = 0.671, p = 0.045). Additionally, rs1049544 was significantly associated with large-artery disease prevalence (GG vs. CC: AOR = 0.489, p = 0.028; GG + GC vs. CC: AOR = 0.527, p = 0.033), and rs1130643 (TT vs. TC: AOR = 0.362, p = 0.039) was associated with cardioembolism prevalence in ischemic stroke subtype analysis. In haplotype analysis, G-G (rs1049544/rs7695558; odds ratio = 4.942, p = 0.001) and C-T (rs1049544/rs1049539; odds ratio = 0.776, p = 0.043) haplotypes were associated with ischemic stroke prevalence. Although some genotypes were not individually associated with ischemic stroke, the presence of the rs1049544 C allele appeared to enhance risk. Conclusions: These findings suggest that SPARCL1 polymorphisms are associated with ischemic stroke and may be considered potential biomarkers for risk assessment. Full article

Image dehazing is critical for visual enhancement and a wide range of computer vision applications. Despite significant advancements, challenges remain in preserving fine details and adapting to diverse, non-uniformly degraded scenes. To address these issues, we propose a novel image dehazing method that introduces a contrastive learning framework, enhanced by the InfoNCE loss, to improve model robustness. In this framework, hazy images are treated as negative samples and their clear counterparts as positive samples. By optimizing the InfoNCE loss, the model is trained to maximize the similarity between positive pairs and minimize that between negative pairs, thereby improving its ability to distinguish haze artifacts from intrinsic scene features and better preserving the structural integrity of images. In addition to contrastive learning, our method integrates a multi-scale dynamic feature fusion with a hybrid attention mechanism. Specifically, we introduce dynamically adjustable frequency band filters and refine the hybrid attention module to more effectively capture fine-grained, cross-scale image details. Extensive experiments on the RESIDE-6K and RS-Haze datasets demonstrate that our approach outperforms most existing methods, offering a promising solution for practical image dehazing applications. Full article

Significant efforts have been dedicated to developing controlled-release systems for the effective management of colorectal cancer. In this study, a once-daily, delayed-release regorafenib (REG) tablet was fabricated using 3D printing technology for the treatment of colorectal cancer. For this, a hydrogel containing 80 mg of the drug in a matrix of hyaluronic acid, carboxymethyl cellulose, Pluronic F127, and glycerol was prepared to incorporate into the shell cavity of tablet via a pressure-assisted microsyringe (PAM). The shell was printed from an optimized ink formulation of Soluplus^®, Eudragit^® RS-100, corn starch 1500, propylene glycol 4000, and talc through melt extrusion-based 3D printing. In vitro release assays showed a drug release rate of 91.1% in the phosphate buffer medium at 8 h and only 8.5% in the acidic medium. Drug release kinetics followed a first-order model. The results showed smooth and uniform layers based on scanning electron microscopy (SEM) and drug stability at 135 °C upon TGA. FTIR analysis confirmed the absence of undesired covalent interactions between the materials. Weight variation and assay results complied with USP standards. Mechanical strength testing revealed a Young’s modulus of 5.18 MPa for the tablets. Overall, these findings demonstrate that 3D printing technology enables the precise fabrication of delayed-release REG tablets, offering controlled-release kinetics and accurate dosing tailored for patients in intensive care units. Full article

This study explores how Turkish Generation Z adapts their fashion consumption behaviours in response to economic crises, particularly focusing on involuntary anti-consumerism. Through a qualitative methodology using semi-structured interviews and purposive sampling, the research captures the coping strategies and emotional experiences of young consumers in Türkiye. A thematic analysis of fifteen interviews reveals an original “8Rs” framework—Reject, Restrict/Reduce, Reuse/Reclaim, Re-find, Reconsider, Re-framing Discounts, Re-direction of Resources, and Emotional Responses—that illustrates both behavioural and psychological adjustments under financial strain. Notably, the study introduces two novel concepts: “recession rush,” a calculated urgency to purchase before price hikes, and “re-direction of resources,” the reallocation of budget from other categories toward fashion purchases. By focusing on a geographically underrepresented context and a pivotal consumer segment, this research contributes new insights to the literature on anti-consumption, economic adaptation, and youth identity expression in crisis economies. Full article

Objectives: Atrial fibrillation (AF) is associated with high risk of ischaemic stroke (IS). Oral anticoagulant therapy (OAT) is the standard of care for stroke prevention, even though its management remains challenging in clinical practice. An emerging problem is embolic events occurring on adequately conducted OAT, the so-called resistant stroke (RS). We aimed to describe pre-stroke prevention therapy, management on hospital discharge, and therapy at follow-up in all patients with AF hospitalized for IS and in the RS subgroup. Methods: We conducted a retrospective monocentric study of patients with known AF hospitalized for an IS. A subgroup with RS was identified. We recorded information on prevention therapy at home, recommended therapy at discharge, and data on outcome and prevention therapy at follow-up. Results: We identified 226 patients, 61% females, median age 84.04 years. Preventive therapy at home was performed in 121 (53.5%) (119 OAT and 2 Left Atrial Appendage Occlusion). At hospital discharge OAT was prescribed to 78.2% of patients. RS was diagnosed in 33 patients whose management at discharge was: same OAT in 12, shift to another Direct Oral Anticoauglant (DOAC) in 5, from DOAC to Vitamin K Antagonist (VKA) and vice versa in 11, non-specified OAT in 4. At final, follow-up of 208 days (range 85–443) 23.3% (34/146) did not assume OAT. OAT was significantly associated with survival probability (p < 0.001). Conclusions: Our findings confirm a scarce adoption of guidelines for AF-related embolic events, even in the absence of absolute contraindication to OAT. RS remains an underexplored clinical entity with empirical management, highlighting the need for targeted research and tailored therapeutic strategies. Full article

Background/Objectives: DGAT1 p. K232A (rs109234250) is a well-established causal variant influencing milk fat and protein content in dairy cattle, but it is often absent from commercial genotyping arrays. PPP1R16A rs109146371 frequently appears as a top signal in genome-wide association studies (GWAS) for milk traits. This study aimed to evaluate the linkage disequilibrium (LD) between these two variants in Japanese Holsteins and assess whether rs109146371 exerts an independent effect on milk traits. Methods: A total of 256 Japanese Holstein cows were genotyped for DGAT1 p. K232A and PPP1R16A rs109146371 using TaqMan SNP assays. LD statistics (r², D′) were computed, and linear mixed-effects models were used to evaluate associations with 305-day milk yield, fat percentage, protein percentage, and solids-not-fat (SNF) percentage. Likelihood ratio tests were conducted to assess the independence of SNP effects. Results: Strong LD was observed between DGAT1 p. K232A and PPP1R16A rs109146371 (r² = 0.91, D′ = 0.9962). Both SNPs showed significant associations with all milk production traits; however, model comparisons indicated that rs109146371 did not improve model fit when K232A was included, suggesting no independent effect. Conclusions: PPP1R16A rs109146371 serves as a proxy for DGAT1 K232A rather than an independent determinant of milk traits. Full article

To enhance both the environmental performance and mechanical properties of phosphate solid waste backfill materials, this study examines the effects of corn straw fibre (CS), rice straw fibre (RS), and jute fibre (JF), each at five lengths (3–15 mm) and five dosages (0.1–0.5 wt%), on the rheological behaviour, mechanical strength, and microstructural characteristics of the backfill slurry. The experimental results showed that the incorporation of natural fibres markedly improved both the compressive and tensile strengths of backfill materials. For example, incorporating CS at a length of 12 mm and a dosage of 0.2 wt% increased the compressive and tensile strengths by 144.4% and 18.8%, respectively. Likewise, RS at 3 mm and 0.2 wt% increased the strengths by 68.3% and 11.9%, while JF at 12 mm and 0.5 wt% enhanced them by 108.2% and 14.9%, respectively. Ion leaching experiments and XPS analyses confirmed that the incorporation of natural fibres effectively adsorbed and immobilized phosphorus and fluorine in phosphogypsum. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses revealed that the improved mechanical strength was primarily attributed to fibre-bridging effects and enhanced fibre–matrix bonding. Furthermore, nuclear magnetic resonance (NMR) analysis demonstrated that incorporating natural fibres reduced the porosity of backfill materials (from 12.9% to 8.14%) while increasing their density. This study provides an experimental foundation for optimizing backfill materials and recommends a 12 mm CS fibre length at a dosage of 0.2 wt% to improve the stability and safety of mine fill structures. Full article

The healthcare industry faces mounting pressure to enhance efficiency and accuracy in logistics operations. Despite its critical role, the sector demonstrates a low adoption rate of logistics automation, with the investment ratio at 14.9%, significantly lower than the industrial average of 18%. This study explores the current state and strategic application of logistics automation in healthcare through 20 in-depth interviews with stakeholders across manufacturers, wholesalers, hospitals, clinics, and pharmacies in South Korea. Analysis revealed that automation adoption is largely contingent on two key factors: annual order volumes and inventory complexity. Companies handling over 100,000 order lines annually and managing over 1000 SKUs were more likely to have adopted or planned automation systems such as AS/RSs, AMRs, or Cube-based AS/RS. The research culminates in a directional map that aligns automation strategies with operational scale and product characteristics. This study contributes novel empirical insights into the fragmented healthcare logistics sector, offering actionable guidance for phased automation implementation based on contextual constraints and stakeholder typologies. Full article

Background/Objectives: As part of the human adaptation to dairy consumption, the presence of the rs4988235-T variant in the MCM6 gene primarily determines lactase persistence in adult European populations, increasing the expression of the lactase-encoding LCT gene. Carriers of the C/C variant are lactose intolerant, while carriers of the T/T or T/C variant have persistent lactase enzyme activity and are able to digest lactose in adulthood. While the association between lactose intolerance and increased cardiovascular risk (CVR) is well-known, the underlying causes have only been partly explored. The present study aimed to investigate the association of rs4988235 polymorphism with significant lipids affecting cardiovascular health and estimated CVR. Methods: The rs4988235 polymorphism was genotyped in 397 subjects from the general Hungarian population and 368 individuals from the Roma population. To characterize the overall lipid profile, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), apolipoprotein AI (ApoAI), and apolipoprotein B100 (ApoB100) levels were measured, and their ratios (TG/HDL-C, LDL-C/HDL-C, and ApoB100/ApoAI) were calculated. Cardiovascular risk was estimated using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCE), Revised Pooled Cohort Equations (RPCE), and the Systematic Coronary Risk Evaluations (SCORE and SCORE2) algorithms. Adjusted linear and logistic regression analyses were performed, with p < 0.05 considered significant. Results: The Roma population had a significantly higher prevalence of the C/C genotype than the general population (65.5% vs. 40.3%, respectively). The results of the adjusted linear regression analysis showed a significant association between the C/C genotype and higher LDL-C level (B = 0.126, p = 0.047) and ApoB100 level (B = 0.046, p = 0.013), as well as a higher LDL-C/HDL-C ratio (B = 0.174, p = 0.021) and a higher ApoB100/ApoAI ratio (B = 0.045, p = 0.002), as well as a lower HDL-C level (B = −0.041, p = 0.049). The C/C genotype was also significantly associated with an increased cardiovascular risk (CVR) as estimated by the SCORE (B = 0.235, p = 0.034), SCORE2 (B = 0.414, p = 0.009), PCE (B = 0.536, p = 0.008), and RPCE (B = 0.289, p = 0.045) but not the FRS. After adjusting the statistical model further for ApoAI and ApoB100 levels, the significant correlation with the risk estimation algorithms disappeared (SCORE: p = 0.099; SCORE2: p = 0.283; PCE: p = 0.255; and RPCE: p = 0.370). Conclusions: Our results suggest that the C/C genotype of rs4988235 is associated with significantly higher ApoB100 and lower ApoAI levels and consequently higher ApoB100/ApoAI ratios, potentially contributing to an increased risk of cardiovascular disease. The results of the statistical analyses suggest that the association between lactose intolerant genotype and cardiovascular risk may be mediated indirectly via modification of the apolipoprotein profile. Full article

Background/Objectives: Isotretinoin is a highly effective therapy for severe acne, but its potential neuropsychiatric adverse reactions (NPsRs) have been controversial. This study evaluated EudraVigilance data from 2005 to 2025 to better understand the frequency, typology, and predictors of such events. Methods: We conducted a retrospective analysis of 33,381 individual case safety reports (ICSRs) related to isotretinoin. Using descriptive statistics, chi-square tests, and logistic regression, we assessed associations between NPsRs and variables such as age, sex, geographic region, and reporter type. Results: A total of 9793 cases (29.3%) involved at least one NPsR. Depression (31%) and suicidal ideation (8.6%) were the most frequently reported symptoms. Adolescents (12–17 years) had the highest proportion of NPsR cases, while male patients and reports submitted by non-healthcare professionals were significantly overrepresented. Reports from non-European Economic Area countries also had slightly increased odds of including NPsRs. All predictors were statistically significant in the logistic regression model, though the explained variance was modest (Nagelkerke R² = 0.065). Conclusions: Neuropsychiatric reactions remain a prominent and persistent signal in isotretinoin pharmacovigilance, particularly among younger patients and non-professional reporters. Although causality cannot be inferred from spontaneous reporting data and confounding factors like acne-related depression cannot be excluded, these findings highlight the clinical value of pre-treatment psychiatric screening, patient-centered education, and proactive mental health monitoring throughout isotretinoin therapy. Full article

:Solvents represent the quiet majority in biomolecular systems, yet modeling their influence with both speed and ri:gor remains a central challenge. This study maps the state of the art in implicit solvent theory and practice, spanning classical continuum electrostatics (PB/GB; DelPhi, APBS), modern nonpolar and cavity/dispersion treatments, and quantum–continuum models (PCM, COSMO/COSMO-RS, SMx/SMD). We highlight where these methods excel and where they falter, namely, around ion specificity, heterogeneous interfaces, entropic effects, and parameter sensitivity. We then spotlight two fast-moving frontiers that raise both accuracy and throughput: machine learning-augmented approaches that serve as PB-accurate surrogates, learn solvent-averaged potentials for MD, or supply residual corrections to GB/PB baselines, and quantum-centric workflows that couple continuum solvation methods, such as IEF-PCM, to sampling on real quantum hardware, pointing toward realistic solution-phase electronic structures at emerging scales. Applications across protein–ligand binding, nucleic acids, and intrinsically disordered proteins illustrate how implicit models enable rapid hypothesis testing, large design sweeps, and long-time sampling. Our perspective argues for hybridization as a best practice, meaning continuum cores refined by improved physics, such as multipolar water, ML correctors with uncertainty quantification and active learning, and quantum–continuum modules for chemically demanding steps. Full article