Search Results (8,024)

Chronic kidney disease (CKD) is a progressive global health challenge. While empagliflozin, a selective SGLT2 inhibitor, is known to attenuate CKD progression through mechanisms beyond glycemic control, the precise molecular pathways remain incompletely characterized and warrant further investigation. This study employed an integrated network pharmacology and molecular docking approach to elucidate the multi-target mechanisms of empagliflozin in CKD. Initial evaluation demonstrated that empagliflozin exhibits favorable physicochemical properties, drug-likeness, and ADMET profiles, supporting its potential as an effective orally administered therapeutic option for CKD management. Network analysis identified 221 shared molecular targets between empagliflozin and CKD-associated genes. Topological analysis of the protein–protein interaction (PPI) network revealed ten critical hub proteins—GAPDH, IL6, EGFR, HSP90AA1, NFKB1, HSP90AB1, MTOR, MAPK3, IL2, and PIK3CA—which serve as key regulators in CKD pathophysiology. Gene Ontology and KEGG pathway enrichment analyses indicated that these shared targets are significantly involved in phosphorylation, signal transduction, and central signaling cascades associated with CKD progression, including the PI3K-Akt, FoxO, HIF-1, and AGE-RAGE pathways. Molecular docking simulations corroborated empagliflozin’s multi-target affinity, demonstrating particularly strong binding energies toward HSP90AB1 (−10.85 kcal/mol), MAPK3 (−9.46 kcal/mol), and EGFR (−9.38 kcal/mol). Empagliflozin maintained stable hydrogen bonding throughout the 200-ns molecular dynamics simulation, primarily with GLN18, GLU42, SER45, ASN46, ASN101, GLY130, and TYR134, underscoring its persistent and well-anchored interaction with HSP90AB1. Collectively, these findings provide crucial mechanistic insights, suggesting that empagliflozin might exerts therapeutic effects by modulating interconnected pathways regulating inflammation, oxidative stress, and metabolic homeostasis, thereby reinforcing its role as a comprehensive, multi-target therapeutic strategy for CKD management. Nonetheless, validation through in vitro experiments remains necessary. Full article

Maternal infection (MI) can increase the risk of neurodevelopmental and behavioural changes. This study examined MI-induced changes in motor coordination through the inflammatory-pathway-mediated epigenetic status of Reln. On gestational day (GD) 10, rats were assigned as (i) Control (Ctrl); (ii) Cronobacter sakazakii (CS) infection on GD-10 through recto-vaginal colonization; (iii) Negative Control (NC) [infected with C. sakazakii and treated with dimethyl sulfoxide (DMSO) 1 h before and 24 h after infection]; and (iv) C. sakazakii-infected rats treated with matrix metalloproteinase inhibitor (MMPI), 1 h before and 24 h after infection (CS + MMPI). Offspring were subjected to footprint analysis and the ladder rung walking test, which revealed that MI caused significant deficits in motor coordination. In addition, MI activated complement components—a disintegrin and metalloproteinase with thrombospondin motifs-1 (ADAMTS-1, C5a)—as well as proinflammatory cytokines such as interleukin-6 (IL-6) and matrix metalloproteinases (MMP-2, MMP-3, and MMP-9). Furthermore, the levels of DNA methyltransferase 3 alpha (DNMT3A), methyl-CpG-binding protein 2 (MeCP2), and histone H3 lysine 4 trimethylation (H3K4me3) were elevated in the CS and NC groups. Concurrently, the level of Reln promoter methylation increased; as a result, mRNA and protein, as well as postsynaptic density protein-95 (PSD-95), levels were decreased. Overall, the findings suggest that MI altered MMP-2/3/9 activity, H3K4me3, and the methylation of Reln, thereby affecting reelin, synaptic protein expression, and motor coordination in an experimental meningitis rat model. Full article

This study investigates the feasibility of utilising alkali-activated slag (AAS) and construction demolition waste (CDW) as cemented paste backfill materials. The fluidity, unconfined compressive strength, bleeding rate, and sulfate resistance of AAS-CDW backfill systems were systematically analysed. Hydration mechanisms were characterised using SEM-EDS and XRD. A novel backfill system and application process were developed and implemented in Jining Coal Mine, Shandong Province. Results indicate that a 30% waste red brick addition enhances 28-day compressive strength by 9.3% and reduces the bleeding rate by 32%, while a 10% fly ash addition optimises slurry fluidity. Notably, the AAS-based backfill exhibits superior mechanical properties and sulfate resistance compared to ordinary Portland cement (OPC)-based systems. The 28-day compressive strength of the AAS backfill reached 5.31 MPa, which is 53.4% higher than that of the OPC backfill, and its strength loss rate after sulfate attack was reduced by 13%. The solid waste utilisation rate of the AAS backfill approaches 100%. Hydration products primarily comprise ettringite (Aft), C-A-S-H gel, and hydrotalcite (HT), resulting in higher compactness than OPC-RA mixtures. Full article

Hair loss, particularly androgenetic alopecia (AGA) and alopecia areata (AA), is a prevalent condition with widespread psychosocial impact. Recently, low-level laser therapy (LLLT) has emerged as a promising non-invasive therapeutic alternative due to its bioregulatory effects and favorable safety profile compared to conventional pharmacological treatments. In this study, we employed fluorescence lifetime imaging microscopy (FLIM) to investigate the effects of red-light irradiation on hair follicle dynamics and the cutaneous microenvironment in a C57BL/6 mouse model. A hair regeneration model was established to evaluate the efficacy of 650 nm red-light irradiation (bandwidth ± 20 nm). Then, the skin tissue was stained with hematoxylin and eosin (H&E) and followed by FLIM analysis to provide a multidimensional assessment of tissue morphology and metabolic status. Results showed that red-light irradiation significantly increased hair follicle numbers and enhanced adenosine triphosphate (ATP) levels in the skin tissue. FLIM analysis further revealed prolonged fluorescence lifetime values across different epidermal and dermal layers in the irradiated group, indicating significant alterations in the skin metabolic microenvironment. Furthermore, phasor plot analysis enabled precise differentiation between hair follicles and their surrounding skin structures, highlighting FLIM’s high sensitivity and accuracy in evaluating hair growth. In conclusion, this study has provided novel imaging-based insights into the mechanisms of LLLT-induced hair regeneration, highlighting the potential of FLIM as a powerful tool for characterizing the cutaneous microenvironment and quantitatively evaluating phototherapeutic efficacy in future translational applications. Full article

Pulmonary arterial hypertension (PAH) is a severe and progressive cardiopulmonary disorder with limited treatment options. Camellia petelotii (Merr.) Sealy (CP) contains multiple flavonoids and other phytochemicals, but its active compounds and molecular mechanisms in PAH remain unclear. Active compounds of CP were screened by comprehensive literature mining and absorption, distribution, metabolism, and excretion (ADME) evaluation. PAH-related hub targets were identified from transcriptomic data using weighted gene co-expression network analysis (WGCNA), machine learning, and external validation. Functional enrichment, immune infiltration, and single-cell RNA-sequencing analyses were performed to characterize their biological roles and cellular localization. Molecular docking and molecular dynamics simulations assessed compound–target interactions. The effects of CP were further evaluated in hypoxia-induced rat pulmonary artery smooth muscle cells (RPASMCs). Five core bioactive compounds were identified, among which luteolin and quercetin were prioritized for further analysis. HSP90AA1 and ROCK2 were screened as hub targets. Bioinformatic analyses suggested that these targets were mainly associated with the “Lipid and atherosclerosis” pathway, metabolic reprogramming, and modulation of the immune microenvironment. Single-cell analysis showed broad expression of HSP90AA1 and enrichment of ROCK2 in fibroblasts and endothelial cells. Molecular docking and molecular dynamics simulations supported stable binding of luteolin to HSP90AA1. In vitro, CP extract inhibited hypoxia-induced hyperproliferation of RPASMCs and reduced HSP90AA1 protein expression. HSP90AA1 may represent a candidate molecular mediator of CP in PAH, and CP inhibited hypoxia-induced RPASMC proliferation in association with downregulation of HSP90AA1. Full article

This study evaluated changes in upper trapezius muscle stiffness and choroidal blood flow velocity before and after ultrasonic therapy of the trapezius muscle. Participants included 27 healthy young adults in their 20 s (median age [Q1–Q3]: 21.0 [19.3–21.0]) without subjective shoulder pain. All participants received a single-session ultrasound intervention, and no control group was included. Intraocular pressure (IOP), systolic blood pressure (BP), diastolic BP, mean BP, heart rate (HR), ocular perfusion pressure (OPP), and salivary α-amylase (sAA) activity, a marker of autonomic nerve function, were assessed at baseline and after therapy. Stiffness of the upper trapezius muscle was evaluated using shear wave elastography, and choroidal hemodynamics were assessed by measuring the mean blur ratio (MBR), a relative index of macular blood flow velocity, using laser speckle flowgraphy. IOP, systolic BP, diastolic BP, mean BP, HR, OPP, sAA activity, and MBR reduced significantly after therapy. The shear elastic modulus of the trapezius muscle also decreased significantly. However, no significant correlations were observed among the parameters. Among healthy adults in their 20 s without shoulder pain, trapezius muscle ultrasound therapy may enhance parasympathetic activity, contributing to decreases in systemic and choroidal circulatory parameters. These findings indicate that ultrasound therapy for shoulder stiffness may influence local musculoskeletal characteristics, systemic and ocular circulation, and autonomic pathways. Full article

This research-to-practice study presents a design-oriented framework that integrates challenge-based learning (CBL), experiential learning (EL), and authentic assessment (AA) to support competency development in higher education. The framework aligns the stages of CBL (i.e., engagement, investigation, and solution) with Kolb’s experiential learning cycle and core AA principles, including realism, cognitive challenge, and evaluative judgement. Learning activities are structured around real-world challenges that reflect professional practice, enabling a coherent progression from experience to reflection, conceptualisation, and evaluation, and supporting the systematic development and assessment of student competencies. A single case study illustrates the application of the framework in industrial engineering education, implemented across six interdisciplinary modules at a private university in Mexico. Students engaged in process improvement projects within six small and medium-sized enterprises, fostering problem solving, decision making, and evaluative judgement in authentic contexts. The findings indicate that the framework supports the development of problem-solving and communication competencies, demonstrating its design coherence and practical feasibility. The framework provides structured guidance for educators to align learning objectives, activities, and assessments within CBL environments. However, limitations related to pedagogical integration and the single-case design constrain the generalisability of the findings. Future research should explore cross-disciplinary applications, longitudinal competency development, and adaptation to emerging educational contexts. Full article

The article discusses the methods for classifying processes for testing and processing metals by plastic deformation, based on the characteristics of their stress–strain state. The basic methods for determining the stress and strain states using fundamental scalar quantities representing the stress and strain tensors are discussed. Equations have been derived for the quantitative determination of the type of stress–strain state through a combination of principal stresses, represented as the strain rigidity of the deformation mode. A deformable work-hardening alloy, AA7075, from the database Quantor Form 8.2.4 software product, is used, which is deformed at room temperature with an analysis of elastic–plastic deformations. A classification of deformation processes for testing and processing metals by plastic deformation is proposed, using the stress triaxiality parameter and the strain rigidity coefficient. Some 2D and 3D diagrams have been created based on simulation modeling of plastic deformation processes using virtual tools, allowing the grouping of processes according to the measured principal stresses and their combinations, which represent the stress triaxiality and strain rigidity of the deformation mode. By determining the type of grouping in these diagrams and the change in the stress–strain state with increasing strain levels, the characteristic features of the deformation processes used in materials testing and in the processing metals by plastic deformation of metals/alloys have been confirmed. Full article

This study presents a comparison between the results of process parameter optimization for the deep drawing of an AA5754-O automotive fuel tank, which utilizes two different objective functions. The first objective function is the maximum thinning percentage (max. %Thinning) of the formed part, which is a conventional formability index. The second is Q-value, a metric derived from the Thinning Limit Diagram that accounts for both necking-prone (excessive thinning) and wrinkling-prone (thickening) regions. The experiments were conducted using finite element simulation to model the forming behavior under an inscribed central composite design within the response surface methodology. Three process parameters, which are well known to be important for controlling material flow and achieving a balance between wrinkling and excessive thinning in deep drawing, were varied: blank holder pressure, the height of the male drawbead, and the radius of the female drawbead. Refined second-order response surface models were developed for both objective functions. Optimization based on the response surface models showed that, for the max. %Thinning objective function, the final part exhibited 19.46% maximum thinning but suffered from substantially higher wrinkling, as indicated by a maximum thickening of 36.39%. In contrast, the Q-value-based optimization resulted in a more balanced formability condition, with maximum thinning of 21.74% and maximum thickening of 13.17%. Moreover, the normalized density of elements in the safe zone of the Thinning Limit Diagram was higher, indicating an improvement in formability robustness. Therefore, this study highlights the limitations of conventional thinning-based optimization and demonstrates the potential of the Q-value as an extended practical quantitative formability tool that can simultaneously address necking and wrinkling in sheet metal forming, as presented through the studied automotive fuel tank on behalf of complex components. Full article

Inadequate Municipal Solid Waste (MSW) management constitutes a critical environmental challenge, as approximately 40% of waste reaches uncontrolled disposal sites where open-air incineration generates significant air, soil, and water pollution. The objective of this study was to evaluate the MSW Environmental Management System (EMS) in Chilpancingo de los Bravo, Guerrero, Mexico, through sustainability indicators and applicable Mexican environmental regulations to identify operational and structural deficiencies that guide a comprehensive improvement in its management. The methodology comprised an analysis of the EMS via the Municipal Development Plan, the identification of environmental indicators and applicable Mexican standards, and an evaluation of the EMS through waste characterization and sustainability metrics. A sample of 208 kg was defined in accordance with standards NMX-AA-015-1985 and NMX-AA-022-1985. The results indicate a generation rate of approximately 350 tons per day (1.2 kg/capita/day), with municipal collection coverage of 70% of the territory across 24 daily routes operated by 30 vehicles. Indicators revealed a recycling rate of 4.86%, collection coverage of 79.66%, a 0% treatment rate due to the absence of composting or material recovery facilities, and 95% of waste directed to the Final Disposal Site (FDS). These findings demonstrate substantial deficiencies in the current EMS, highlighting that the systematic application of indicators is an effective diagnostic tool for identifying gaps and guiding evidence-based improvements in MSW governance. Full article

The present study investigated the effects of low-protein (LP) diets on growth performance, intestinal morphology, apparent ileal digestibility (AID), and jejunal amino acid (AA) transporter mRNA expression in heat-stressed Pekin ducks. A total of 108 fourteen-day-old male ducks were randomly allotted to three treatments, each with six replicates of six birds: a thermoneutral (TN) group fed a control (CON) diet, a heat stress (HS) group fed the CON diet, and an HS-LP group fed the LP diet. Ducks were maintained at 22 °C (TN) or 30 °C (HS and HS-LP) for 3 wk. The CON and LP diets contained 17.5% and 16.0% CP, respectively, with similar AA profiles. Compared with the TN group, the HS group showed reduced BW, ADFI, and ADG and increased F:G (p < 0.05). Compared with the HS group, the HS-LP group showed higher BW and ADG and lower F:G (p < 0.05), although BW and ADG remained lower than in the TN group. HS decreased villus height (VH), jejunal villus height-to-crypt depth (VH:CD) ratios, and goblet cell counts (p < 0.05). Compared with the HS group, the HS-LP group showed higher jejunal and ileal VH:CD ratios and lower ileal CD (p < 0.05), whereas VH and goblet cell counts were not restored to TN values. Although AID of CP and AAs did not differ between the TN and HS groups, the HS-LP group showed higher AID of CP and AAs than the HS group (p < 0.05). In addition, the HS-LP group showed lower PEPT1 and higher LAT1 mRNA expression (p < 0.05). In conclusion, a reduction in dietary CP from 17.5% to 16.0% partially alleviated HS-induced growth depression and intestinal morphological impairment and was accompanied by increased AID of AAs and altered mRNA expression of jejunal AA transporters. Full article

Brain tumor classification from magnetic resonance imaging, which is also known as MRI, plays a sensitive role in computer-assisted diagnosis systems. In recent years, deep learning models have achieved high classification accuracy. However, their sensitivity to adversarial perturbations has become an important reliability concern in medical applications. This study suggests a robust brain tumor classification framework that combines non-negative matrix factorization (NNMF or NMF), lightweight convolutional neural networks (CNNs), and diffusion-based feature purification. Initially, MRI images are preprocessed and converted into a non-negative data matrix, from which compact and interpretable NNMF feature representations are extracted. Statistical metrics, including AUC, Cohen’s d, and p-values, are used to rank and choose the most discriminative components. Then, a lightweight CNN classifier is trained directly on the selected feature groups. To improve adversarial robustness, a diffusion-based feature-space purification module is introduced. A forward noise method followed by a learned denoiser network is used before classification. System performance is estimated using both clean accuracy and robust accuracy under powerful adversarial attacks created by AutoAttack. The experimental results show that the proposed framework achieves competitive classification performance while significantly enhancing robustness against adversarial perturbations. The findings presuppose that combining interpretable NNMF-based representations with a lightweight deep approach and diffusion-based defense technique supplies an effective and reliable solution for medical image classification under adversarial conditions. Full article

Functionally graded AA2024/B4C metal matrix composites were fabricated via mechanical alloying and hot pressing to investigate structure–property–radiation shielding relationships. Single-layer, two-layer, and three-layer architectures with varying B4C contents were systematically produced. Microstructural homogeneity and phase constitution were examined using SEM/EDS and XRD, while thermal stability was evaluated by thermogravimetric analysis. Density and porosity measurements were conducted to assess the influence of reinforcement distribution and functional grading on densification behavior. Gamma radiation shielding performance was experimentally evaluated using a 152Eu source and an HPGe detector over a wide photon energy range. Key shielding parameters, including linear and mass attenuation coefficients, half-value layer, tenth-value layer, mean free path, and radiation protection efficiency, were determined. The results reveal that functional grading significantly enhances radiation attenuation compared to monolithic composites. The three-layer AA2024/B4C composite exhibited the highest attenuation coefficients and the lowest HVL, TVL, and MFP values at all investigated energies, achieving nearly 100% improvement in shielding efficiency relative to unreinforced AA2024. These findings demonstrate that controlled B4C distribution and layered composite architecture provide a synergistic improvement in thermal stability, physical integrity, and radiation shielding performance, positioning functionally graded AA2024/B4C composites as efficient lightweight materials for advanced radiation shielding applications. These results indicate that the developed functionally graded AA2024/B4C composites are promising candidates for advanced radiation shielding applications in nuclear facilities, aerospace structures, and medical radiation protection systems, where lightweight and high-performance materials are critically required. Full article

Jasmonate ZIM-domain (JAZ) proteins, as core negative regulatory factors of the jasmonic acid (JA) signaling pathway, play a key role in the growth and development of plants and the response to biotic and abiotic stress. In this study, 11 flax JAZ members were identified, all of which contain a ZIM domain and a Jas domain. LuJAZs comprise 3–16 exons, encoding 187–808 amino acids (aa) with molecular weights ranging from 20.24 to 88.76 kDa and isoelectric points (PI) of 5.68–9.77. They are all hydrophilic proteins located in the nucleus. These 11 LuJAZ genes are divided into five subfamilies and are unevenly distributed on chromosomes. Transcriptome and qRT-PCR analyses revealed that six LuJAZ genes, including LUSG00004384, LUSG00030782, LUSG00016742, LUSG00004390, LUSG00010997, and LUSG00029783, are significantly induced by JA. The protein–protein interaction (PPI) prediction and analysis of differential expression genes (DEGs) suggest that the MYC2 gene (LUSG00028070) may play a role in the JA-induced response. This study provides a theoretical basis for further exploring the function of the JAZ family in flax. Full article

This study aimed to evaluate the compensatory effects of amino acid (AA) supplementation on laying hens fed a low-protein diet, focusing on production performance, egg quality, blood immunity, total tract retention, and intestinal health. A total of 180 Hy-Line Brown laying hens (35 weeks old) were randomly allocated to three dietary treatments with 12 replicates (5 hens/replicate): (1) control diet (15.90% crude protein, CON), (2) reduced-protein diet (15.20% crude protein, NG), and (3) reduced-protein diet supplemented with 400 g/t methionine, 400 g/t lysine, and 300 g/t threonine (15.20% crude protein, LAA). Over the 12-week experimental period, production parameters were monitored weekly. The results showed that compared to the NG group, AA supplementation significantly increased laying rates during weeks 1–4 (p < 0.05) and reduced the feed-to-egg ratio during weeks 9–12 (p < 0.05), with a 3.10% decrease in feed conversion ratio (FCR). By week 12, the NG group exhibited lower Haugh unit values than both the CON and LAA groups (p < 0.05), indicating improved egg quality with AA supplementation. Serum analysis revealed elevated immunoglobulin Y levels and upregulated expression of the anti-inflammatory cytokine IL-10 in the LAA group (p < 0.05). Total tract retention of crude protein (CP) and phosphorus (P) was significantly enhanced in the LAA group compared to CON and NG groups (p < 0.05). However, in terms of cecal microbiota, no significant differences were observed among the experimental groups. These findings demonstrate that AA supplementation alleviates the adverse effects of low-protein diets by enhancing nutrient utilization and immune modulation, thereby improving productive performance, egg quality, and total tract retention in laying hens. Full article