Search Results (2,324)

Urban heat island conditions increase heat exposure and constrain safe outdoor activities. Urban forests can mitigate thermal loads; however, stand morphology can produce divergent microclimates. We aimed to quantify how stand type (open vs. closed), season (spring, summer, fall), and activity intensity (MET 1.0–6.0) jointly modulate thermal comfort and to identify season-specific optimal MET levels in an urban forest in Daejeon, Republic of Korea. We combined site-specific 3D canopy modeling with hourly Predicted Mean Vote (PMV) simulations driven by AMOS tower data (2023–2024). Comfort was defined as |PMV| ≤ 0.5. Analyses included seasonal means, Cliff’s delta, and generalized estimating equation logistic models to estimate the SITE × SEASON × MET interactions and predict comfort probabilities. Across most seasons and MET levels, C1 was more comfortable than C2. However, at MET 1.0 in summer, the pattern was reversed, which may reflect the canopy shading and associated decreases in mean radiant temperature (MRT) of C2. Comfort peaked at MET 2.0–3.0 and declined sharply at ≥4.5 MET. The three-way SITE × SEASON × MET interaction was significant (p < 0.001). The season-specific optimal MET values under our boundary conditions were 3.0 (spring), 2.0–2.5 (summer), and 3.0 (fall). These simulation-based PMV-centered findings represent model-informed tendencies. Nevertheless, they support actionable guidance: prioritize high-closure stands for low-intensity summer use, leverage open stands for low-to-moderate activities in spring and fall, and avoid high-intensity programs during warm periods. These results inform the programming and design of urban-forest healing and recreation by matching stand type and activity intensity to season to maximize comfortable hours. Full article

Concrete is a widely used construction material. This research investigates the effect of adding tree branch waste and stone dust as substitutes for coarse and fine aggregates on concrete’s physical and mechanical properties. The results show that these additives significantly impact weight and compressive strength. The weight comparison for 10% additive concrete was 7.28 kg at 7 and 14 days, while for 20% additive concrete, it was 7.02 kg at 7 days and 7.06 kg at 14 days. Normal concrete weighed 7.50 kg at 7 days and 7.66 kg at 14 days. The planned compressive strength (K250 or F’c: 20 MPa) for 28 days was met, with samples containing 10% and 20% additives exceeding the planned strength. However, increased use of these materials led to a reduction in compressive strength. Therefore, the addition of tree branches and stone dust should be limited to 10%, as the highest compressive strength was obtained at this percentage. This research suggests that using tree branch waste and stone dust as partial substitutes for aggregates can reduce concrete’s weight while maintaining its strength. Limiting the addition to 10% is recommended for optimal results. Full article

Ciclopirox (CPX), a topical antifungal agent of the N-hydroxypyridone class, has gained renewed interest for its potential anticancer, antiviral, antibacterial, and neuroprotective effects. However, due to lack of reliable validated bioanalytical methods, current insights into its pharmacokinetics profile beyond topical use remain limited. To support therapeutic repurposing, we developed and validated a rapid, sensitive LC-MS/MS method for systemic pharmacokinetic evaluation in mice. The method employs methyl derivatization of CPX’s N-hydroxy group, producing methylated CPX (Me-CPX) for improved chromatographic performance which was subsequently retained on the Atlantis^TM T3 C18 reverse phase column. Concentration of CPX is determined indirectly based on the measured response of Me-CPX. The method achieved excellent recovery, a 4-min rapid runtime, sensitivity with LLOQ of 3.906 nM (0.81 ng/mL), and a linear range up to 1000 nM (r ≥ 0.9998). All validation parameters including intra- and inter-day accuracy, precision, matrix effects, stability and dilution integrity met the criteria defined by regulatory International Council for Harmonisation (ICH) M10 bioanalytical method validation guidelines. Application of the method to in vitro plasma protein binding studies revealed high protein binding (>99%) of CPX in both human and mice plasma. Preliminary PK analysis following intravenous and oral administration in CD-1 mice demonstrated moderate systemic exposure after oral dosing, with an estimated absolute bioavailability of 52.5%. These findings establish the method’s suitability and robustness for preclinical and future clinical development of CPX as a repurposed therapeutic agent. Full article

Micronutrients and nutraceuticals play crucial roles in wound healing and tissue regeneration, supporting various physiological processes. This review aims to synthesize and evaluate the functions of various micronutrients and nutraceuticals, emphasizing the synergistic interactions among different nutrients that facilitate wound healing processes. A thorough literature review was performed using electronic databases, including PubMed, Scopus, Web of Science, Embase, Google Scholar, and Cochrane Library, to identify molecular studies, animal models, randomized controlled trials, and observational human studies published up to January 2000. Two independent reviewers screened the articles, extracted data, and evaluated the Risk of Bias using the Risk of Bias 2 (RoB 2) tool for the 190 studies that met the inclusion criteria. Evidence suggests that bioactive compounds found in functional foods and dietary supplements can help prevent chronic conditions and promote wellness beyond basic nutrition. Vitamins A, C, and E, as well as minerals such as zinc, selenium, and iron, are essential for cell proliferation and the formation of new tissues. Additionally, nutraceuticals, including omega-3 fatty acids, glutamine, arginine, and polyphenols, exhibit anti-inflammatory and antioxidant properties, which promote healing and reduce the risk of infection. Probiotics and other bioactive compounds in nutraceuticals contribute to maintaining the balance of microbiota, reducing inflammation, and stimulating cell regeneration. Significant variability was noted in study design, sample size, intervention dosage, and outcome measures. This evidence underscores the necessity for further well-designed clinical trials to determine the optimal dosages and combinations for specific wound types across diverse patient populations. This systematic review was prospectively registered in PROSPERO (ID: 1072091). Full article

Background/Objectives: Drug discovery is a lengthy and expensive process, taking an average of 10 years and more than USD 2 billion from target discovery to drug approval. It is even more challenging in complex diseases due to disease heterogeneity and limited knowledge about the underlying mechanisms. We present a novel computational framework that integrates network analysis, statistical mediation, and deep learning to identify causal target genes and repurposable small-molecule candidates. Methods: We applied weighted gene co-expression network analysis (WGCNA) and bidirectional mediation analysis (causal WGCNA) to transcriptomic data from idiopathic pulmonary fibrosis (IPF) patients to identify genes causally linked to the disease phenotype. These genes were used as a phenotypic signature for deep learning-based compound screening using the DeepCE model. Results: Using RNA-seq data from 103 IPF patients and 103 controls, we identified seven significantly correlated modules and 145 causal genes. Five of these genes (ITM2C, PRTFDC1, CRABP2, CPNE7, and NMNAT2) were predictive of disease severity in IPF. Our compound screening identified several promising candidates, such as Telaglenastat (GLS1 inhibitor), Merestinib (MET kinase inhibitor), and Cilostazol (PDE3 inhibitor), with significant inverse correlation with the IPF-specific gene signature. Conclusions: This study demonstrates the utility of combining causal inference and deep learning for drug discovery. Our framework identified novel gene targets and therapeutic candidates for IPF, offering a scalable strategy for phenotype-driven drug discovery and repurposing. Full article

Metabolic syndrome refers to a group of conditions that commonly occur together, including abdominal obesity, high blood pressure, elevated blood sugar, high triglyceride levels, and low high-density lipoprotein cholesterol (HDL). These factors collectively increase the risk of cardiovascular disease, diabetes, and cognitive impairment. Recent research has identified a connection between metabolic syndrome and cognitive disorders such as mild cognitive impairment and vascular dementia (VaD). Mulberry (Morus alba L.) is a natural source of bioactive compounds with antioxidant, anti-inflammatory, and lipid-regulating properties. This meta-analysis assessed the potential of mulberry extract as an adjunctive treatment for metabolic risk factors linked to vascular dementia. We systematically reviewed randomized controlled trials (RCTs) published up to May 2025 that compared mulberry extract to placebo or standard care in adults with metabolic disorders. Fifteen trials including 1202 participants met the inclusion criteria. The primary outcomes were fasting glucose, fasting insulin, liver enzyme levels, lipid profiles, and inflammatory markers such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP). The pooled results indicated that mulberry supplementation improved blood sugar control and lowered total cholesterol, low-density lipoprotein cholesterol (LDL), triglycerides, fasting blood glucose, glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), and inflammatory markers. Aspartate aminotransferase (AST) improved, whereas alanine aminotransferase (ALT) showed no significant change. Subgroup analyses revealed that greater benefits were associated with shorter treatment durations and doses below 500 milligrams per day. Furthermore, extracts from different parts of the mulberry plant showed varying effects on lipid and glucose metabolism. None of the included trials directly measured cognitive or neurovascular outcomes, so any potential neurovascular protection is inferred from changes in metabolic and inflammatory markers rather than demonstrated. In summary, these findings suggest that mulberry extract may be a promising complementary approach for managing metabolic risk factors in people at risk for VaD. However, further large-scale and rigorously designed studies are required to confirm its clinical benefits and to identify the most effective preparations. Full article

Hispanic populations in the U.S. have a high prevalence of type 2 diabetes and its complications. It has been proposed that interventions targeting multiple levels and domains of influence are needed to address health disparities, but more evidence is needed regarding the most effective approaches. We aimed to review the effects of non-pharmacological interventions on glycemic control among Hispanic persons with diabetes, overall and by level and domain of intervention. A systematic review (PubMed, Scopus, PsycInfo, CINAHL; 1985–2019) identified randomized trials reporting HbA1c outcomes for Hispanic populations. Article review, data extraction, and risk of bias assessment were completed by independent reviewers. Level and domain of intervention were assigned based on the National Institute on Minority Health and Health Disparities Research Framework. Random-effects meta-analyses estimated pooled effect sizes. Quality of evidence was rated based on the GRADE framework. Forty-eight trials met inclusion criteria, representing various Hispanic populations (n = 18 Mexican, n = 5 Puerto Rican, n = 1 Dominican, n = 4 multiple, n = 20 unspecified) and enrolling 9185 total participants. Overall, interventions decreased HbA1c by −0.32% (95% CI: −0.44% to −0.20%, I² = 68%, strength of evidence: moderate). Multi-level, multi-domain interventions decreased HbA1c by −0.41% (−0.61% to −0.21%, I² = 74%, strength of evidence: moderate). Few interventions addressed community (n = 3), society (n = 0), or physical/built environment (n = 1). Non-pharmacological interventions have modestly decreased HbA1c among Hispanic persons with diabetes. Multi-level, multi-domain interventions are promising, but more research is needed on interventions that target social and environmental structures. Full article

Compounds, which rely on metabolism to exhibit toxicity, pose a challenge for next-generation risk assessment (NGRA). Since many of the currently available non-animal new approach methods (NAMs) lack metabolic activity, their use may lead to an underestimation of the true hazard to humans (false negative predictions). We explored here strategies to deal with metabolite-mediated toxicity in assays for developmental neurotoxicity. First, we present an overview of substances that may serve as potential positive controls for metabolite-related neurotoxicity. Then, we demonstrate, using the MitoMet (UKN4b) assay, which assesses the adverse effects of chemicals on neurites of human neurons, that some metabolites have a higher toxic potency than their parent compound. Next, we designed a strategy to integrate elements of xenobiotic metabolism into assays used for (developmental) neurotoxicity testing. In the first step of this approach, hepatic post-mitochondrial fractions (S9) were used to generate metabolite mixtures (“metabolisation module”). In the second step, these were applied to a NAM (exemplified by the UKN4b assay) to identify metabolite-mediated toxicity. We demonstrate the applicability and transferability of these approaches to other assays, by an exemplary study on the basis of the cMINC (UKN2) assay, another NAM of the developmental neurotoxicity in vitro battery. Based on the experience gained from these experiments, we discuss key issues to be addressed if this approach is to be used more broadly for NAM in the NGRA context. Full article

Background: Metabolic syndrome (MetS) is a major risk factor for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), especially in Middle Eastern populations with a high metabolic burden. This study aimed to evaluate the predictive utility of different lipid ratios, including triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C), total cholesterol (TC)/HDL-C, low-density lipoprotein (LDL-C)/HDL-C, and non-HDL-C/HDL-C, for identifying MetS. In addition, we aimed to characterise the underlying metabolic dysregulation using the most predictive lipid ratio by comparing metabolomic profiles between high-risk (T3) and low-risk (T1) groups. Method: We conducted a cross-sectional study using data from 2179 Qatari adults without CVD and/or T2DM. The predictive value of each lipid ratio for MetS was compared. Untargeted metabolomics was performed to profile metabolic changes between T3 and T1. Results: After adjustment for age, sex, and BMI, TG/HDL-C showed the highest discriminative ability for MetS (AUC = 0.896, 95% CI: 0.88–0.91; OR = 4.36, 95% CI: 3.63–5.28, p < 0.0001). In pairwise AUC comparisons, TG/HDL-C outperformed LDL-C/HDL-C (p = 2.6 × 10⁻⁴, after correction for multiple comparisons), with no significant differences versus other ratios. The high-risk group exhibited raised levels of phosphatidylethanolamines, phosphatidylinositols, and diacylglycerols, and lower levels of sphingomyelins and plasmalogens. These lipid classes have been suggested to be implicated in insulin resistance and metabolic dysfunction. Elevated monoacylglycerols were identified in high-TG/HDL-C groups, representing a previously underreported pattern. Conclusions: The TG/HDL-C ratio showed a better association with MetS compared with other lipid ratios and was linked to distinct metabolomic signatures. These findings suggest potential value for early risk evaluation, but longitudinal and mechanistic studies are needed to confirm clinical applicability. Full article

Background: A number of viruses are oncogenic. These include the human papilloma virus (HPV), Epstein–Barr virus (EBV), Kaposi sarcoma human herpes virus 2/human herpes virus 8 (KSHHV/HHV8), hepatitis B virus, (HBV), hepatitis C virus (HCV), Merkel cell polyoma virus (McPyV), and the human T-cell leukemia virus type 1 (HTLV-1). These viruses cause malignancies ranging from carcinomas, sarcomas, lymphomas, to leukemias. This review aims to study the effects and efficacy of vaccines against these viruses and the cancers they cause in their prevention and treatment. Methods: The literature in the past 30 years was searched employing Scopus and Google Scholar using the keywords “oncogenic viruses, HPV, EBV, KSHHV, HHV8, Polyoma virus, HTLV-1, COVID-19, carcinoma, sarcoma, lymphoma, leukemia, anti-virus vaccines”. Results: Prophylactic vaccines against the HPV and HBV are highly effective in preventing and reducing the incidence of uterine cervical and hepatocellular carcinomas. Prophylactic vaccines against other oncogenic viruses have been less successful, though efficacious in some experimental animals. Therapeutic vaccines are still mostly under evaluation and development. Conclusions: Identification of oncogenic viruses has rendered anti-viral vaccines conspicuous tools for preventing and treating cancers they cause. Many endeavors for the development of such vaccines have been met with limited success, apart from the very effective anti-HPV and anti-HBV vaccines in universal vaccination programs. With the development of new vaccine technologies, it is hoped that effective vaccines against other oncogenic viruses will be developed in the future. Full article

Previous studies conducted by our research groups have demonstrated that the HGF/c-Met signaling pathway promotes the proliferation and migration of MSCs in the antlers of Tarim red deer. However, the role and mechanism of this gene in the osteogenic differentiation of antler MSCs remain unclear. In this study, we used antler MSCs as experimental materials. CRISPR/Cas9 technology was employed to knock out the HGF gene, and lentivirus-mediated overexpression of the HGF gene was constructed in antler MSCs. Subsequently, antler MSCs were induced to undergo osteogenic differentiation in vitro. Alizarin Red staining was employed to identify calcium nodules, while the expression levels of various osteogenic differentiation marker genes were assessed using immunohistochemistry, RT-qPCR, and Western blotting techniques. The findings indicated that the HGF gene facilitates the osteogenic differentiation of antler MSCs. Analysis of genes associated with the PI3K/Akt and MEK/ERK signaling pathways demonstrated that in antler MSCs with HGF gene knockout, the expression levels of PI3K/Akt and MEK/ERK pathway genes were significantly downregulated on days 7 and 14 of osteogenic differentiation (p < 0.05). In contrast, antler MSCs with HGF gene overexpression exhibited a significant upregulation of the PI3K/Akt and MEK/ERK signaling pathways on days 4 and 6 of osteogenic differentiation (p < 0.01). These findings suggest that the HGF gene in antlers enhances the osteogenic differentiation of MSCs by activating the PI3K/Akt and MEK/ERK pathways. Full article

Menopause is a natural and inevitable part of life for women, leading to many physical and psychological changes accompanied by declining estrogen levels. This systematic review aimed to evaluate the effect of curcumin, due to its antioxidant and anti-inflammatory properties, on postmenopausal outcomes in women. This comprehensive analysis of RCTs (randomized controlled trials) published in the last decade was selected through a search of PubMed, Wiley, Scopus, and Web of Science (PROSPERO Identifier: CRD42024549735). Study selection and data extraction were performed using exclusion and inclusion criteria according to the PICOS framework (P: Population, I: Intervention, C: Comparison, O: Outcomes, S: Study designs). Of the twelve studies that met the criteria, 11 had a low-risk bias, but reports were conflicting on serum estradiol levels, bone density markers, and vasomotor symptoms; no significant effects on physical, psychological, or sexual functions were observed. For cardiometabolic biomarkers, short-term curcumin intake showed no significant effects, while long-term interventions using bioavailable forms of curcumin showed improvements in serum fasting glucose, fasting insulin, HOMA-IR (Homeostatic Model Assessment of Insulin Resistance), and lipid parameters. There are a limited number of studies examining the effect of curcumin intake on menopause-related outcomes. While overdose has been observed in some studies attempting to restore estradiol levels, no significant effects have been observed. However, curcumin intake impacts postmenopausal symptoms (e.g., improving symptoms of osteoporosis) through its antioxidant and anti-inflammatory effects. Different forms and doses, combinations, and durations of interventions may influence outcomes. Better-designed studies are needed to understand the potential effects of curcumin intake during menopause. Full article

This study investigated how different extraction parts of raw materials and different flocculation methods affect the extraction yield, structure, and properties of sodium alginate. The aim was to improve the quality of sodium alginate and provide theoretical guidance for upstream enterprises. In this study, Lessonia nigrescens (LN) was used as a raw material. The alkali treatment conditions were optimized. The optimal extraction conditions were determined to be a 2% sodium carbonate concentration, a duration of 4 h, a material-to-liquid ratio of 1:40, and a temperature of 60 °C, achieving an extraction yield of 43.03%. LN was categorized into blades, stipes, holdfasts, and whole seaweed for comparative analysis, and sodium alginate was flocculated using the acid, calcium, and ethanol methods. Structural and physicochemical analyses showed that the mannuronic acid/guluronic acid (M/G) ratios of the twelve sodium alginate samples ranged from 5.73 to 8.76. The LN part had a greater influence on the M/G ratio than the flocculation method. The relative molecular weight (2343–3074 kDa) and viscosity (170–331 mPa·s) exhibited consistent trends. For the same part, the effect of the flocculation method on the molecular weight followed the order ethanol > acid > calcium. The physicochemical properties of the extracted sodium alginate met the requirements specified in the physicochemical index standard GB 1886.243-2016 of China. Full article

This study investigates the influence of rear setback geometry and façade design parameters on microclimatic conditions, indoor thermal comfort, and energy performance in multi-story residential buildings in hot arid climates, addressing the growing need for climate-responsive design in regions with extreme temperatures and high solar radiation. Despite increasing interest in sustainable strategies, the combined effects of urban geometry and building envelope design remain underexplored in these environments. A coupled simulation framework was developed, integrating ENVI-met for outdoor microclimate modeling with Design Builder and EnergyPlus for dynamic building performance analysis. A total of 270 simulation scenarios were examined, combining three rear setback aspect ratios (1.5, 1.87, and 2.25), three window-to-wall ratios (10%, 20%, and 30%), three glazing types (single-, double-, and triple-pane), and two wall insulation states, using customized weather files derived from microclimate simulations. Global sensitivity analysis using rank regression and multivariate adaptive regression splines identified the glazing type as the most influential parameter (sensitivity index ≈ 0.99), especially for upper floors. At the same time, higher aspect ratios reduced peak Physiological Equivalent Temperature (PET) by up to 5 °C and decreased upper-floor cooling loads by 37%, albeit with a 9.3% increase in ground-floor cooling demand. Larger window-to-wall ratios lowered lighting energy consumption by up to 35% but had minimal impact on cooling loads, whereas wall insulation reduced annual cooling demand by up to 29,441 kWh. The results emphasize that integrating urban morphology with optimized façade components, particularly high-performance glazing and suitable aspect ratios, can significantly improve thermal comfort and reduce cooling energy consumption in hot arid residential contexts. Full article

Urban planning in arid climates must overcome numerous nonclimatic constraints that often result in outdoor thermal discomfort. This is particularly evident in Béchar, a city in southern Algeria known for its long, intense summers with temperatures frequently exceeding 45 °C. This study investigates the influence of urban morphology on thermal comfort and explores architectural and digital solutions to enhance energy performance in buildings. This research focuses on Béchar’s city center, where various urban configurations were analyzed using a multidisciplinary approach that combines typomorphological and climatic analysis with numerical simulations (ENVI-met 3.0 and TRNSYS 16). The results show that shaded zones near buildings have lower thermal loads (under +20 W/m²), while open areas may reach +100 W/m². The thermal comfort rate varies between 22% and 60%, depending on wall materials and occupancy patterns. High thermal inertia materials, such as stone and compressed stabilized earth blocks (CSEBs), reduce hot discomfort hours to under 1700 h/year but may increase cold discomfort. Combining these materials with targeted insulation improves thermal balance. Key recommendations include compact urban forms, vegetation, shading devices, and high-performance envelopes. Early integration of these strategies can significantly enhance thermal comfort and reduce energy demand in Saharan cities. Full article