Search Results (29)

Background: Manganese (Mn) is an essential trace element with antioxidant properties; however, excessive exposure may contribute to inflammation and vascular dysfunction. Hair analysis provides an indicator of long-term Mn exposure. This study evaluated the relationship between hair Mn levels, acute coronary syndrome (ACS), coronary artery disease (CAD) severity, and cardiovascular risk factors, with particular emphasis on metabolic status in a cardiometabolic population. Methods: Hair Mn concentration was measured using inductively coupled plasma optical emission spectrometry (ICP-OES) in 80 patients (mean age 67 ± 11 years; 28.8% women) undergoing coronary angiography for suspected ACS. Final diagnoses included stable CAD (N = 42) and ACS [ST-elevation myocardial infarction (STEMI) N = 17, non-ST-elevation myocardial infarction (NSTEMI) N = 12, and unstable angina (UA) N = 9]. CAD severity was quantified using the SYNTAX score and the Coronary Artery Surgery Study Score (CASSS). Associations with clinical variables were assessed using non-parametric tests and Spearman correlations. The median SYNTAX score was 13.8 (range 0.0–68.5), and the median hair Mn concentration was 0.22 ppm (range 0.01–1.65). Results: SYNTAX scores were higher in ACS than in stable CAD (p = 0.027), with the highest values observed in NSTEMI. Hair Mn levels did not differ among diagnostic groups and showed no association with CASSS or SYNTAX (R = −0.11; p = 0.348). No differences were detected with respect to sex, smoking, prior myocardial infarction, hypertension, hyperlipidemia, or type 2 diabetes. A modest inverse correlation was observed between hair Mn and body mass index (BMI) in unadjusted analysis (R = −0.25; p = 0.03), but this association was not robust after correction for multiple comparisons, suggesting a potential exploratory link between manganese homeostasis and cardiometabolic status. Conclusions: Although hair Mn concentration was not associated with angiographic indices of CAD severity or ACS subtypes, the observed relationship with BMI may indicate a role of Mn homeostasis in cardiometabolic regulation. Larger prospective studies are required to clarify these associations. Full article

Ensuring the crashworthiness of heavy-duty truck cabs is essential for reducing occupant fatalities and improving passive safety in commercial vehicles. Regulatory frameworks such as UNECE Regulation No. 29 (R29) define structural integrity requirements through full-scale destructive impact tests, which are costly and limit iterative design. In this study, an integrated experimental–numerical methodology is presented for the impact assessment of a real Iveco Eurocargo 120E18 truck cab reconstructed using high-resolution 3D scanning. The scanned geometry was used to generate a dimensionally accurate CAD model of the load-bearing cab structure, which was analysed using explicit finite element simulations in ANSYS Academic Mechanical and CFD Teaching package under impact conditions compliant with UNECE R29 and implemented according to the Swedish regulation VVFS 2003:29. In parallel, a full-scale physical pendulum impact test was performed on the same cab using a cylindrical impactor with a diameter of 580 mm, a length of 1800 mm, and a mass of approximately 1000 kg, impacting the upper region of the A-pillar. The experimental setup was instrumented using high-speed optical measurements and an accelerometer to capture impact kinematics and structural response. The numerical predictions showed good agreement with experimental results in terms of acceleration–time histories, absorbed energy evolution, and structural deformation, with differences generally below 6%. Critical regions susceptible to local buckling and plastic collapse were consistently identified in both approaches, while preservation of the driver survival space was confirmed. The results demonstrate that scan-based finite element models, when properly calibrated and validated, can reliably reproduce certification-level impact behaviour. The proposed workflow provides a robust and cost-effective framework for regulatory pre-validation, structural optimisation, and digitalisation of crashworthiness assessment for heavy-duty truck cabs. Full article

The Auditing of Natural Resource Assets (ANRA) is an institutional arrangement in China that evaluates leading cadres’ performance in the management and protection of natural resource assets at the time of their departure from office. Although existing studies have examined the institutional design and implementation mechanisms of ANRA, empirical evidence on its direct impact on farmland protection remains limited. Moreover, previous research has largely overlooked spatial heterogeneity in ANRA’s effects across diverse local contexts such as economic regions and different grain functional areas. To narrow these gaps, this study generated a panel data set, covering 275 prefecture-level cities from 2011 to 2017. The study employed a staggered difference-in-differences (DID) model to empirically evaluate the effects of ANRA on farmland protection. The results show that the implementation of the ANRA policy has significantly increased farmland area in pilot regions, with an average annual increase of approximately 5800 hectares relative to non-pilot regions during the post-policy period. The policy effects varied across regions and the positive impact is more pronounced in the eastern regions and major grain-producing regions. Mechanism evidence suggests that the ANRA contributes to farmland protection by reshaping local land-use behavior. Based on these findings, the paper recommends promoting the normalization and standardization of ANRA, strengthening land use regulation to enhance resource allocation efficiency, and improving the design of policy classifications based on regional heterogeneity. Full article

Following the launch of the Sustainable Development Goals (SDGs) process at the Rio+20 Summit, China has progressively strengthened sustainability-oriented considerations in development target setting and administration cadre performance assessment, which provides an institutional window to examine how the transformation of development goals reshapes urban land supply patterns. This study develops a spatial general equilibrium model and uses panel data for 286 prefecture-level cities in China from 2007 to 2021 to examine how the transformation of development goals affects urban land supply patterns. The results show that higher economic growth targets significantly expand total land supply, raise the ratio of industrial to residential land supply, and tighten floor-area-ratio (FAR) regulation. “Soft constraint” wording dampens the effect on land supply scale but strengthens the effects on land supply structure and FAR regulation, while the degree of vertical and horizontal target escalation generates substantial heterogeneity in these relationships. Moreover, after governance shifted from growth-oriented to sustainability-oriented objectives, the marginal effectiveness of using land supply structure and FAR regulation to deliver predetermined growth targets declined significantly. This study provides empirical evidence and policy-relevant insights for improving sustainability-oriented target accountability systems and urban governance incentive mechanisms. Full article

Background: Chemokine CCL5 may drive inflammation and vascular risk in advanced liver disease, but its cardiovascular implications are unclear. Secreted by hepatic, endothelial, macrophage, and lymphocytic cells, CCL5 is involved in cytokine regulation. Its serum levels rise in acute liver injury and hepatocellular carcinoma (HCC), but decline with fibrosis progression in end-stage liver disease (ESLD). CCL5 has also been linked to atherosclerosis. This study aimed to evaluate serum CCL5 levels in ESLD patients listed for liver transplantation (LT) and to assess their potential role as markers of cardiovascular (CV) risk and portal hypertension. Methods: We conducted an observational cohort study. Between 2019 and 2022, patients with ESLD evaluated for LT were enrolled. Data on liver pathology, CV risk, and laboratory parameters were collected. Serum CCL5 concentrations were measured using Sigma Aldrich^® CCL5 ELISA kits (MilliporeSigma, St. Louis, MO, USA). The database was analyzed with IBM^® SPSS^® Statistics version 20 (Chicago, IL, USA). Results: Overall, 46 patients were included, 50% with viral hepatitis and 28.3% with alcohol-related liver disease. HCC was present in 37% of cases. The median CV risk scores (CAD_LT = 7, mCAD_LT = 7, CAR_OLT = 18) placed the population at moderate CV risk. Serum CCL5 levels did not vary significantly between viral vs. non-viral cirrhosis (5511.8 vs. 6272.5 pg/mL, p = 0.15) and were not influenced by the presence of HCC (6098.4 vs. 5771.3 pg/mL, p = 0.55). We did not detect a correlation with MELD score (p = 0.21) or CV risk scores (CAD_LT: p = 0.58; mCAD_LT: p = 0.70; CAR_OLT: p = 0.22). Patients with thrombocytopenia (<100,000/µL, 54.3%) or a history of esophageal variceal ligation had lower CCL5 levels (5170.9 vs. 6750.8 pg/mL, p = 0.002 and 4252.0 vs. 6237.5 pg/mL, p = 0.003, respectively). Similarly, patients with a history of previous variceal bleeding and spontaneous bacterial peritonitis (SBP) had lower levels of CCL5 (4373.8 vs. 6119.9 pg/mL, p = 0.02 and 3404.3 vs. 6606.7 pg/mL, p = 0.01, respectively). We found a negative correlation between CCL5 and QTc interval duration (τ = −0.216, p = 0.037), left ventricle size (LV: τ = −0.235, p = 0.027), and pulmonary artery pressure (RV/RA gradient: τ = −0.225, p = 0.03). CCL5 correlated positively with the inflammatory markers C-reactive protein (CRP) (τ = 0.246, p = 0.018) and fibrinogen (r = 0.216, p = 0.04). Conclusions: In liver transplant candidates, serum CCL5 is not associated with cardiovascular risk scores or coronary atherosclerotic burden, but is inversely associated with clinical markers of portal hypertension severity. These findings suggest that CCL5 may serve as a potential non-invasive surrogate marker of portal hypertension rather than a cardiovascular risk biomarker in ESLD. Full article

This comprehensive review explores the critical roles of microRNAs (miRNAS) in cardiovascular diseases, emphasizing their regulatory functions in gene expression and their involvement in disease progression. miRNAS are small, evolutionarily conserved non-coding RNAs that regulate gene expression post-transcriptionally and play essential roles in various cardiac conditions, including fibrosis, cardiac remodeling, apoptosis, ischemia/reperfusion injury, hypertrophy, heart failure, arrhythmias, coronary artery disease (CAD), congenital heart diseases (CHDs), cardiomyopathies, and valvular heart disease (VHD). miRNAS are increasingly recognized as sensitive and specific biomarkers for early diagnosis, disease monitoring, and evaluation of therapeutic responses across the cardiovascular disease spectrum. Ischemia/reperfusion injury leads to significant cardiac damage through elevated oxidative stress, mitochondrial dysfunction, and apoptosis. CAD, a major contributor to global morbidity and mortality, is primarily driven by atherosclerosis and chronic inflammation. Cardiac hypertrophy is initially an adaptive response to stress but may progress to heart failure if sustained. Arrhythmias arise from electrical disturbances such as reentry, abnormal automaticity, and triggered activity. Heart failure is a complex and progressive syndrome marked by poor prognosis and increasing global prevalence. VHD involves intricate molecular alterations, including myocardial fibrosis and calcification, which contribute to disease progression and adverse outcomes. Cardiomyopathies—including hypertrophic, dilated, restrictive, and arrhythmogenic forms—are influenced by genetic mutations, systemic diseases, and disrupted molecular signaling. CHDs, the most common congenital malformations, stem from structural abnormalities in cardiac development and remain a major cause of infant morbidity and mortality. Novel therapeutic methods, such as antisense oligonucleotides, miR mimics, and exosome-based delivery mechanisms, demonstrate the translational promise of miRNAs in the realm of personalized cardiovascular medicine. However, issues such as small sample sizes, inconsistent results, interspecies differences, and delivery challenges restrict the clinical application of miRNA-based therapies. This review integrates mechanistic insights, critiques the quality of available evidence, and identifies translational shortcomings. It highlights the diagnostic, prognostic, and therapeutic potential of miRNAs in reshaping cardiovascular disease treatment. Full article

Background/Objectives: Depression is a mental disorder that can lead to self-harm or suicidal thoughts if left untreated. Psychiatrists often face challenges in identifying the most effective courses of treatment for patients with depression. Two widely recommended depression-related therapies are selective serotonin reuptake inhibitors (SSRIs) and repetitive transcranial magnetic stimulation (rTMS). However, their response rates are approximately 50%, which is relatively low. This study introduces a computer-aided decision (CAD) system designed to determine the effectiveness of depression therapies and recommends the most appropriate treatments for patients. Methods: Each channel of the EEG is plotted in two-dimensional (2D) space via a novel technique called the amplitude polar map (APM). In each channel, the 2D plot of APM is utilized to extract distinctive features via the binary pattern of five successive lines method. The extracted features from each channel are fused to generalize the pattern of EEG signals. The most relevant features are selected via the neighborhood component analysis algorithm. The chosen features are input into a simple feed-forward neural network architecture to classify the EEG signal of a depressed patient into either a respondent to depression therapies or not. The 10-fold cross-validation strategy is employed to ensure unbiased results. Results: The results of our proposed CAD system show accuracy rates of 98.06% and 97.19% for predicting the outcomes of SSRI and rTMS therapies, respectively. In SSRI predictions, prefrontal and parietal channels such as F7, Fz, Fp2, P4, and Pz were the most informative, reflecting brain regions involved in emotional regulation and executive function. In contrast, rTMS prediction relied more on frontal, temporal, and occipital channels such as F4, O2, T5, T3, Cz, and T6, indicating broader network modulation via neuromodulation. Conclusions: The proposed CAD framework holds considerable promise as a clinical decision-support tool, assisting mental health professionals in identifying the most suitable therapeutic interventions for individuals with depression. Full article

The rugose surface trait in pepper (Capsicum annuum L.), marked by ridges and depressions on the fruit epidermis, is linked to improved fruit texture. To investigate its regulatory basis, histological, textural, and transcriptomic differences, contrasting genotypes were analyzed. Histological analysis revealed that disorganized epidermal cell layers contribute to rugosity, with morphological differences emerging around 10 days post-anthesis (DPA). A computer-aided design (CAD)-based rugosity index (RI) was developed and showed strong correlation with sensory rugosity scores (R² = 0.659, p < 0.001). Texture analysis demonstrated that increasing surface rugosity was associated with reduced rupture force and hardness, as well as elevated pectinase activity. Comparative transcriptome profiling identified 10 differentially expressed genes (DEGs) related to microtubule dynamics (e.g., CA03g18310 and CA09g13510) and phytohormone signaling (e.g., CA03g35180 and CA08g12070), which exhibited distinct spatial and temporal expression patterns. These findings suggest that coordinated cytoskeletal remodeling and hormonal regulation drive epidermal disorganization, leading to surface rugosity and altered fruit texture. The study provides novel insights into the molecular basis of fruit surface morphology and identifies promising targets for breeding high-quality pepper cultivars. Full article

Our multi-omics investigation of pepper fruit coloration dynamics demonstrates that the coordinated regulation of flavonoid accumulation and chlorophyll retention underpins the distinct pigmentation patterns between dark green (XHB) and light green (QL2017) cultivars. Through the integrated analysis of three developmental stages (10–30 DPA), we identified 989 differentially accumulated metabolites (DAMs) and 810 differentially expressed genes (DEGs), with flavonoid biosynthesis, phenylpropanoid metabolism, and chlorophyll turnover pathways pinpointed as central regulatory hubs. Notably, key metabolites such as quercitrin, kaempferol-3-O-rhamnoside, and cinnamic acid were significantly enriched in dark green fruits (XHB), coinciding with enhanced antioxidant activity and delayed chlorophyll degradation. Transcriptomic data revealed the coordinated upregulation of chlorophyll biosynthesis genes (COX15, POR) and light-harvesting complex components (Lhcb1, Lhcb2), while PAO—a pivotal chlorophyll catabolism gene—also exhibited elevated expression. Co-expression network analysis highlighted scopoletin GTase, F5H, CCR, and CAD as hub genes regulating flavonoid biosynthesis. qRT-PCR validation confirmed high consistency with transcriptomic trends (r > 0.85, p < 0.01). Our findings propose a synergistic model wherein flavonoid accumulation and chlorophyll metabolic dynamics jointly orchestrate green fruit pigmentation, offering novel insights and molecular targets for the precision breeding of pepper fruit coloration. Full article

The development of different phenotypes of coronary artery (CA) lesions is regulated via many various factors, such as pro-inflammatory agents, zinc-dependent endopeptidases, growth factors and circulating microRNAs (miRs). To evaluate the expression levels of miR-34a, miR-145 and miR-222, tumor necrosis factor α (TNF-α), matrix metalloproteinases (MMP-1, -9, -13 and -14) and vascular endothelial growth factor (VEGF) in patients with different phenotypes of coronary artery disease (CAD): ischemia/angina with non-obstructive coronary arteries (INOCA/ANOCA) and obstructive CAD (oCAD) compared with a control group. This cross-sectional observational study included 157 subjects with a verified CAD diagnosis (51 patients with INOCA, 76 patients with oCAD and 30 healthy volunteers). The expression of miR-34a, miR-145 and miR-222 (RT-PCR) and the levels of VEGF, TNF-α, MMP-1, MMP-9, MMP-13 and MMP-14 (ELISA) were estimated in plasma samples. A higher concentration of MMP-9 was found in oCAD-group samples compared to the INOCA/ANOCA group. The INOCA/ANOCA group was characterized by higher levels of TNF-α. Based on multivariate regression analysis, a mathematical model predicting the type of CA lesion was constructed. MiR-145 was the independent predictor of INOCA/ANOCA (p = 0.006). Changes in concentrations of MMP-9 and MMP-14 were found in both investigated CAD groups, with MMP-9 levels being significantly higher in obstructive CAD samples than in INOCA/ANOCA, which confirms the role of inflammation in the development of atherosclerosis. A multivariate regression analysis allowed us to achieve a model that can predict the phenotype of stable CAD, and MiR-145 can be assumed as an independent predictor of INOCA/ANOCA. Full article

Bacteria respond to metal pollution through sensors that control the uptake and the detoxification machineries. Specificity in metal recognition is therefore a prerequisite for triggering the appropriate response, particularly when facing a mixture of metals. In response to Cu⁺, the purple bacterium Rubrivivax gelatinosus induces the efflux Cu⁺-ATPase CopA by the Cu⁺ regulator CopR. However, genetic analyses have suggested the presence of additional regulators. Here, we show that CadR, the Cd²⁺ sensor, is involved in Cd²⁺ and Cu⁺ tolerance and demonstrate that CopR and CadR share common target genes. Interestingly, expression of the Cu⁺ detoxification and efflux (CopI/CopA) system was induced by Cd²⁺ and downregulated in the double mutant copRcadR⁻. This double mutant was more sensitive to low Cu⁺ concentration than the single copR⁻ mutant, and accumulation of coproporphyrin III pointed to a significantly decreased expression of CopA. Furthermore, analyses of Cd²⁺ toxicity in the cadR⁻ mutant suggested that although CopR is Cu⁺ selective, CopR is involved in Cd²⁺ response since the addition of Cu⁺ alleviates Cd²⁺ toxicity. Based on our current knowledge of metal transport across the inner membrane, Cd²⁺ and Cu⁺ do not share common efflux routes nor do they share common regulators. Nevertheless, the crosstalk between Cd²⁺ and Cu⁺ tolerance systems is demonstrated in the present study. The modulation of Cu⁺ detoxification by a Cd²⁺ regulator in vivo places emphasis on the relaxed selectivity, under elevated metal concentration, in MerR regulators. Full article

Coronary artery disease (CAD) is one of the most common types of cardiovascular disease and can lead to a heart attack as plaque gradually builds up inside the coronary arteries, blocking blood flow. Previous studies have shown that polymorphisms in the PAI-1 gene are associated with CAD; however, studies of the PAI-1 3′-untranslated region, containing a miRNA binding site, and the miRNAs that interact with it, are insufficient. To investigate the association between miRNA polymorphisms and CAD in the Korean population based on post-transcriptional regulation, we genotyped five polymorphisms in four miRNAs targeting the 3′-untranslated region of PAI-1 using real-time PCR and TaqMan assays. We found that the mutant genotype of miR-30c rs928508 A > G was strongly associated with increased CAD susceptibility. In a genotype combination analysis, the combination of the homozygous mutant genotype (GG) of miR-30c rs928508 with the wild-type genotype (GG) of miR-143 rs41291957 resulted in increased risk for CAD. Also, in an allele combination analysis, the combination of the mutant allele (G) of miR-30c rs928508 and the wild-type allele (G) of miR-143 rs41291957 resulted in increased risk for CAD. Furthermore, metabolic syndrome and diabetes mellitus showed synergistic effects on CAD risk when combined with miR-30c rs928508. These results can be applied to identify CAD prognostic biomarkers among miRNA polymorphisms and various clinical factors. Full article

UV-B stress destroys the photosynthetic system of Rhododendron chrysanthum Pall. (R. chrysanthum), as manifested by the decrease of photosynthetic efficiency and membrane fluidity, and also promotes the accumulation of lignin. The MYB (v-myb avian myeloblastosis viral oncogene homolog) family of transcription factors can be involved in the response to UV-B stress through the regulation of lignin biosynthesis. This study indicated that both the donor and recipient sides of the R. chrysanthum were significantly damaged based on physiological index measurements made using OJIP curves under UV-B stress. The analysis of bioinformatics data revealed that the RcTRP5 transcription factor exhibits upregulation of acetylation at the K68 site, directly regulating the biosynthesis of lignin. Additionally, there was upregulation of the K43 site and downregulation of the K83 site of the CAD enzyme, as well as upregulation of the K391 site of the PAL enzyme. Based on these findings, we conjectured that the RcTRP5 transcription factor facilitates acetylation modification of both enzymes, thereby indirectly influencing the biosynthesis of lignin. This study demonstrated that lignin accumulation can alleviate the damage caused by UV-B stress to R. chrysanthum, which provides relevant ideas for improving lignin content in plants, and also provides a reference for the study of the metabolic regulation mechanism of other secondary substances. Full article

MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression post-transcriptionally and are crucial in lipid metabolism. ATP-binding cassette transporter A1 (ABCA1) is essential for cholesterol efflux from cells to high-density lipoprotein (HDL). Dysregulation of miRs targeting ABCA1 can affect cholesterol homeostasis and contribute to coronary artery disease (CAD). This study aimed to investigate the expression of miRs targeting ABCA1 in human monocytes, their role in cholesterol efflux, and their relationship with CAD. We included 50 control and 50 CAD patients. RT-qPCR examined the expression of miR-33a-5p, miR-26a-5p, and miR-144-3p in monocytes. Logistic regression analysis explored the association between these miRs and CAD. HDL’s cholesterol acceptance was analyzed using the J774A.1 cell line. Results showed that miR-26a-5p (p = 0.027) and ABCA1 (p = 0.003) expression levels were higher in CAD patients, while miR-33a-5p (p < 0.001) levels were lower. Downregulation of miR-33a-5p and upregulation of ABCA1 were linked to a lower CAD risk. Atorvastatin upregulated ABCA1 mRNA, and metformin downregulated miR-26a-5p in CAD patients. Decreased cholesterol efflux correlated with higher CAD risk and inversely with miRs in controls. Reduced miR-33a-5p expression and increased ABCA1 expression are associated with decreased CAD risk. miR deregulation in monocytes may influence atherosclerotic plaque formation by regulating cholesterol efflux. Atorvastatin and metformin could offer protective effects by modulating miR-33a-5p, miR-26a-5p, and ABCA1, suggesting potential therapeutic strategies for CAD prognosis and treatment. Full article

Disturbed remodeling of the extracellular matrix (ECM) is frequently observed in several high-prevalence pathologies that include fibrotic diseases of organs such as the heart, lung, periodontium, liver, and the stiffening of the ECM surrounding invasive cancers. In many of these lesions, matrix remodeling mediated by fibroblasts is dysregulated, in part by alterations to the regulatory and effector systems that synthesize and degrade collagen, and by alterations to the functions of the integrin-based adhesions that normally mediate mechanical remodeling of collagen fibrils. Cell-matrix adhesions containing collagen-binding integrins are enriched with regulatory and effector systems that initiate localized remodeling of pericellular collagen fibrils to maintain ECM homeostasis. A large cadre of regulatory molecules is enriched in cell-matrix adhesions that affect ECM remodeling through synthesis, degradation, and contraction of collagen fibrils. One of these regulatory molecules is Transient Receptor Potential Vanilloid-type 4 (TRPV4), a mechanically sensitive, Ca²⁺-permeable plasma membrane channel that regulates collagen remodeling. The gating of Ca²⁺ across the plasma membrane by TRPV4 and the consequent generation of intracellular Ca²⁺ signals affect several processes that determine the structural and mechanical properties of collagen-rich ECM. These processes include the synthesis of new collagen fibrils, tractional remodeling by contractile forces, and collagenolysis. While the specific mechanisms by which TRPV4 contributes to matrix remodeling are not well-defined, it is known that TRPV4 is activated by mechanical forces transmitted through collagen adhesion receptors. Here, we consider how TRPV4 expression and function contribute to physiological and pathological collagen remodeling and are associated with collagen adhesions. Over the long-term, an improved understanding of how TRPV4 regulates collagen remodeling could pave the way for new approaches to manage fibrotic lesions. Full article