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18 pages, 3199 KB  
Article
ST32da, a Novel Salvia miltiorrhiza-Derived ATF3 Inducer, Alleviates Obesity-Related Diabetic Nephropathy in Mouse Models
by Hsi-Hsien Chen, Tzu-Ling Tseng, Hsiao-Fen Li, Ya-Ting Hsieh, Tu Tuan Tran, Yueh-Lin Wu and Heng Lin
Cells 2025, 14(23), 1893; https://doi.org/10.3390/cells14231893 - 28 Nov 2025
Viewed by 749
Abstract
It is necessary to find novel therapeutic strategies for obesity-related diabetic nephropathy (DN) that target both metabolic dysfunction and renal inflammation. ST32da derived from Salvia miltiorrhiza (a well-recognized Traditional Chinese Medicine) induces activating transcription factor 3 (ATF3), a negative regulator of inflammation and [...] Read more.
It is necessary to find novel therapeutic strategies for obesity-related diabetic nephropathy (DN) that target both metabolic dysfunction and renal inflammation. ST32da derived from Salvia miltiorrhiza (a well-recognized Traditional Chinese Medicine) induces activating transcription factor 3 (ATF3), a negative regulator of inflammation and metabolic stress. However, the effects of ST32da on obesity-related DN remain underexplored. We investigated the therapeutic potential of ST32da, a synthetic ATF3 inducer derived from Salvia miltiorrhiza, in mitigating obesity-related DN in both in vivo and in vitro models. The Nephroseq database analysis was performed to explore the relationship between Atf3 expression and DN progression. ST32da was administered to db/db knockout and DBA mice to establish obesity-related DN models, and a high-fat diet (HFD)-induced mouse model of obesity-related DN was used to investigate the effects of Atf3 knockout. Molecular and biochemical analyses were conducted in cultured mesangial cells to elucidate the underlying mechanisms. ATF3 deficiency worsened obesity-related DN, increasing glomerular fibrosis, mortality, and inflammation. ST32da restored ATF3 levels and reduced renal injury, glomerular expansion, and pro-inflammatory cytokine expression (e.g., IL-6, TGFβ, TNFα). ST32da-treated mice exhibited reduced hepatic lipid accumulation and improved serum lipid profiles. In mesangial cells, ST32da localized to the cytoplasm and increased ATF3 activity, which suppressed RARRES1 expression and cytokine signaling. Mechanistically, ATF3 interacted with HDAC2 to repress NF-κB—dependent inflammatory gene expression. The findings suggest ST32da is a promising therapeutic candidate for obesity-related DN and associated metabolic disturbances, acting through ATF3 induction to suppress renal inflammation, lipotoxicity, and fibrosis. Full article
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13 pages, 1897 KB  
Article
Screening and Identification of Drought-Sensitive and Drought-Tolerant Poplar Germplasm Based on Short-Term Physiological and Biochemical Differences
by Lili Fan, Luozhong Tang, Zheng Zuo, Wei Fan, Haiqing Yang and Qi Zhou
Forests 2025, 16(11), 1750; https://doi.org/10.3390/f16111750 - 20 Nov 2025
Viewed by 374
Abstract
Drought responses in poplar are genotype-dependent, yet standardized metrics for quantifying drought tolerance remain scarce. Here, we employed logistic modeling of relative electrolyte leakage (REC) for the first time in poplar to derive clone-specific semi-lethal polyethylene glycol (PEG) concentrations (LC50), transforming [...] Read more.
Drought responses in poplar are genotype-dependent, yet standardized metrics for quantifying drought tolerance remain scarce. Here, we employed logistic modeling of relative electrolyte leakage (REC) for the first time in poplar to derive clone-specific semi-lethal polyethylene glycol (PEG) concentrations (LC50), transforming a traditional descriptive assay into a quantitative, high-throughput drought-injury metric. Six elite Populus cultivars were exposed to increasing PEG concentrations, and their REC curves were fitted using a logistic function (R2 = 0.885−0.981). The derived semi-lethal PEG concentration (LC50) ranged from 7.99% in ‘PZ1’ (drought-sensitive, SS) to 13.44% in ‘YX2’ (drought-tolerant, ST), enabling clear classification. Under 10% PEG stress, ST maintained leaf water content (LWC) at 73%, while SS dropped to 63%. Malondialdehyde (MDA) content doubled in SS (44.7 nmol·g−1 FW) but increased by only 25% in ST (33.5 nmol·g−1 FW). Gas exchange analysis revealed that SS exhibited approximately twice the reduction in net photosynthetic rate (Pn), transpiration rate (Tr), and stomatal conductance (Gs) compared to ST, with intercellular CO2 accumulation (Ci) occurring only in SS—indicating both stomatal and non-stomatal limitations. Osmolyte profiling showed that SS accumulated large amounts of soluble sugars (Ss) (+128%) and proline (Pro) (+230%), whereas ST maintained stable soluble protein (Sp) levels and only moderately increased proline (+120%). Antioxidant capacity differed markedly: catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) activities increased by 5.6-, 1.8-, and 2.0-fold in ST, respectively, compared to 3.4-, 1.3-, and 1.7-fold in SS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) of ten physiological traits explained 89% of the total variance (R2X = 0.954, Q2 = 0.973), identifying POD, SOD, CAT, and Pro as the most discriminative variables (VIP > 1). This four-marker signature converts a conventional dose–response assay into a rapid, low-cost screening module that can be deployed in robotic phenotyping platforms. Specifically, the high-ranking genotype ‘YX2’ is recommended for immediate use in water-limited plantations and as a robust parent for next-generation dryland breeding programs. Full article
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16 pages, 2422 KB  
Article
Cold-Pressed Walnut-Oil Adulteration with Edible Oils Detection Using Vis-NIR Spectroscopy
by Georgiana Fediuc, Mariana Spinei and Mircea Oroian
Foods 2025, 14(22), 3877; https://doi.org/10.3390/foods14223877 - 13 Nov 2025
Viewed by 614
Abstract
The aim of this study is to evaluate the usefulness of UV-Vis-NIR spectroscopy as a tool for detecting the adulteration of cold-pressed walnut oil and other edible oils (rapeseed, sunflower, and soybean oils) at varying percentages. The spectra were recorded between 200 and [...] Read more.
The aim of this study is to evaluate the usefulness of UV-Vis-NIR spectroscopy as a tool for detecting the adulteration of cold-pressed walnut oil and other edible oils (rapeseed, sunflower, and soybean oils) at varying percentages. The spectra were recorded between 200 and 1800 nm, but the analyses focused on 350–1650 nm due to high UV and NIR absorption. Color was determined in CIEL*a*b* coordinates to achieve the differences among the samples. The spectra were submitted to several pre-treatment (none, normalization, SNV, MSC, baseline/detrend, first/second derivative, and 1st-order smoothing) to improve the statistical model’s parameters. The differentiation of the samples was carried out using an unsupervised method (principal component analysis—PCA) and two supervised methods (linear discriminant analysis—LDA and partial least squares linear discriminant analysis—PLS-DA). Partial least squares regression (PLS-R) was used for predicting the degree of adulteration. Separation between the authentic and adulterated samples was visible in the PCA scores plot, primarily along the spectral regions of 420–500 nm (pigment-related absorption band) and 1150–1450 nm (lipid-associated band). PLS-DA was superior to DA for the discrimination of authentic/adulterated samples, with baseline spectra of 350–1650 nm yielding a 100% overall accuracy and near-perfect accuracy with MSC (98.48%). PLS-R was able to predict the adulteration level, depending on the pre-treatment applied. Full article
(This article belongs to the Special Issue Emerging Approaches for the Detection of Food Fraud and Adulteration)
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9 pages, 1034 KB  
Article
Are Dichorionic Twin Pregnancies Resulting from In Vitro Fertilization Different from Spontaneous Dichorionic Twin Pregnancies? A Retrospective Cohort Study
by Ahmet Zeki Nessar, Şebnem Karagün, Fikriye Işıl Adıgüzel, Şule Gül Aydın, Serdar Aykut, Aslıhan Kurt, Süleyman Cansun Demir, Mete Sucu and İsmail Cüneyt Evrüke
J. Clin. Med. 2025, 14(22), 8000; https://doi.org/10.3390/jcm14228000 - 11 Nov 2025
Viewed by 572
Abstract
Background: We aimed to compare the perinatal outcomes of dichorionic/diamniotic twin (DC/DA) pregnancies resulting from in vitro fertilization (IVF) with those resulting from spontaneous DC/DA pregnancies. Methods: The study group included 99 women with DC/DA pregnancies resulting from IVF, and the [...] Read more.
Background: We aimed to compare the perinatal outcomes of dichorionic/diamniotic twin (DC/DA) pregnancies resulting from in vitro fertilization (IVF) with those resulting from spontaneous DC/DA pregnancies. Methods: The study group included 99 women with DC/DA pregnancies resulting from IVF, and the control group included 92 women with spontaneous DC/DA pregnancies. Maternal demographic characteristics (age, parity, and gravidity), pre-existing conditions (chronic hypertension and pregestational diabetes mellitus), and obstetric history were recorded. Pregnancy outcomes included gestational age at delivery, number of fetuses, and mode of delivery. The antepartum complications that we evaluated include first- and second-trimester bleeding, placenta previa, preterm birth, fetal growth restriction (FGR), oligohydramnios, and tocolytic use. The obstetric complications that we assessed include prematurity, twin-to-twin transfusion syndrome (TTTS), and hydrops fetalis. Additionally, neonatal data such as 1st minute and 5th minute Apgar scores, birth weight, neonatal intensive care unit (NICU) admission, presence of congenital anomalies, and neonatal death were recorded, and comparisons were made between the groups. Results: Women in the IVF group were older (34.7 ± 6.9 vs. 32.3 ± 6.1 years, p = 0.03) and more frequently primiparous (73.7% vs. 37.0%, p < 0.001). The mean gestational age at delivery was slightly lower in the IVF group, though this was not statistically significant (34.3 ± 3.5 vs. 35.1 ± 2.5 weeks, p = 0.101). Cesarean delivery was common in both groups, with comparable overall rates (90.9% vs. 94.6%, p = 0.411), but emergency cesarean section occurred more frequently in IVF pregnancies (81.8% vs. 55.8%, p = 0.001). No significant differences were found regarding chronic hypertension or pregestational diabetes. However, several differences were demonstrated in terms of obstetric complications. For example, preterm births and fetal growth restriction (FGR) were significantly more frequent in IVF pregnancies (59.8% vs. 30.4%, p < 0.001), and tocolytic use was also more frequent (56.6% vs. 29.7%, p < 0.001). No significant differences were observed in terms of placenta previa, oligohydramnios, TTTS, hydrops fetalis, and neonatal outcomes. The logistic regression analysis revealed that IVF pregnancies were associated with an increased risk of preterm birth: OR 3.45, 95% CI 1.85–6.78 (p < 0.001); the risk of FGR was also higher in IVF pregnancies: OR 2.11, 95% CI 1.02–4.37 (p = 0.015). However, tocolytic use was not significantly associated with IVF: OR 1.49, 95% CI 0.50–4.44 (p = 0.471). Conclusions: Although DC/DA pregnancies conceived through IVF have a higher risk of preterm birth, fetal growth restriction, and greater use of tocolytic agents than spontaneous DC/DA pregnancies, their neonatal outcomes are similar. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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26 pages, 967 KB  
Article
Neurotransmitter Levels (Dopamine, Epinephrine, Norepinephrine, Serotonin) and Associations with Lipid Profiles in Patients with Prediabetes or Newly Diagnosed Type 2 Diabetes Mellitus
by Roxana Viorela Ahrițculesei, Lidia Boldeanu, Mohamed-Zakaria Assani, Adina Mitrea, Cosmin Vasile Obleaga, Ionela Mihaela Vladu, Diana Clenciu, Mihail Virgil Boldeanu and Cristin Constantin Vere
Int. J. Mol. Sci. 2025, 26(20), 10068; https://doi.org/10.3390/ijms262010068 - 16 Oct 2025
Viewed by 1398
Abstract
Neurotransmitters play a pivotal role not only in central nervous system signaling but also in the regulation of systemic energy metabolism, insulin sensitivity, and cardiovascular function. The contribution of neuroendocrine dysregulation to the development of type 2 diabetes mellitus (T2DM) is increasingly being [...] Read more.
Neurotransmitters play a pivotal role not only in central nervous system signaling but also in the regulation of systemic energy metabolism, insulin sensitivity, and cardiovascular function. The contribution of neuroendocrine dysregulation to the development of type 2 diabetes mellitus (T2DM) is increasingly being recognized; however, the interplay between neurotransmitter levels and lipid/insulin resistance profiles in T2DM and prediabetes (PreDM) remains poorly characterized. We evaluated serum dopamine (DA), norepinephrine (NE), epinephrine (EPI), and serotonin (ST) in 110 individuals with PreDM (n = 40) or newly diagnosed T2DM (n = 70). Extended metabolic profiling included HbA1c, lipid panels, and insulin resistance indices (triglyceride-to-glucose index (TyG), TyG-derived indices). Neurotransmitter levels were compared across body mass index (BMI) categories, gender, and glycosylated hemoglobin A1c (HbA1c) quartiles. We applied multivariable linear regression (MLR) adjusted for body mass index (BMI), age, sex, lipids, penalized logistic regression (predicting T2DM status), and exploratory Spearman correlations with False Discovery Rate (FDR) correction. All four neurotransmitters were significantly higher in T2DM versus PreDM (p < 0.001). In T2DM patients, DA and NE levels increased across HbA1c quartiles, and NE levels were significantly higher in quartile 3 compared to quartile 2 (p = 0.045). In multivariable models, T2DM status was the only consistent predictor of neurotransmitter elevations. Logistic regression identified ST (OR = 8.70) and NE (OR = 3.76) as key discriminators of T2DM status, in addition to HbA1c. Exploratory correlation analyses in T2DM showed trends between EPI and insulin resistance indices (TyG adjusted for waist circumference (TyG-WC), TyG adjusted for waist-to-height ratio (TyG-WHtR)) and between DA and low-density lipoprotein cholesterol (LDL-C), although these did not survive to FDR correction. Neurotransmitter levels are elevated in T2DM and correlate with glycemic and metabolic profiles, suggesting early neuroendocrine involvement in the pathogenesis of diabetes. Serotonin and norepinephrine may serve as adjunctive biomarkers for disease stratification, meriting further prospective and mechanistic investigation. Full article
(This article belongs to the Special Issue Molecular Diagnosis and Treatments of Diabetes Mellitus: 2nd Edition)
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22 pages, 4442 KB  
Article
A Polysaccharide-Rich Ingredient from Hypericum perforatum L. Ameliorates Depression-like and Post-Traumatic Stress Disorder-like Symptoms in Mouse Models
by Zi-Jia Jin, Shuai-Ming Zhu, Fu-Yao Luo, Yue Sun, Chun-Xue Gao, Ting Feng, Hao Ma, Rui Xue, Chang-Wei Li, Lei An and You-Zhi Zhang
Nutrients 2025, 17(20), 3222; https://doi.org/10.3390/nu17203222 - 14 Oct 2025
Cited by 1 | Viewed by 896
Abstract
Background/Objectives: Hypericum perforatum L. (H. perforatum), commonly known as St. John’s wort, has been widely used in clinical practice to treat mental disorders. Previous studies and clinical applications have primarily focused on its alcohol-soluble ingredients. Our research was designed to [...] Read more.
Background/Objectives: Hypericum perforatum L. (H. perforatum), commonly known as St. John’s wort, has been widely used in clinical practice to treat mental disorders. Previous studies and clinical applications have primarily focused on its alcohol-soluble ingredients. Our research was designed to investigate the physicochemical properties, antidepressant-like effects, and anti-post-traumatic stress disorder (PTSD)-like effects of the alcohol-insoluble polysaccharide-rich ingredients from H. perforatum. Meanwhile, the underlying mechanisms were elucidated. Methods: The physicochemical properties of two polysaccharide-rich ingredients, designated as HPP1 and HPP2, were characterized using colorimetric assay, capillary electrophoresis, high-performance gel permeation chromatography, and fourier transform infrared spectroscopy. Behavioral despair tests were conducted to rapidly assess and compare their antidepressant-like effects in mice. Subsequently, behavioral despair mice and foot-shock mice were established to thoroughly explore the impact of HPP2 on depression-like and PTSD-like symptoms. The effects of HPP2 on cerebral pathological changes, neurotrophic factors, and gut microbiota in foot-shock mice were detected through hematoxylin & eosin staining, immunofluorescence staining, and 16S rDNA (V3 + V4 regions) gene sequencing. Results: HPP1 and HPP2 are predominantly composed of arabinose, glucose, galactose, mannose, and galacturonic acid. The molecular weight distribution of HPP1 ranges from 1133 to 67,278 Da, whereas that of HPP2 extends from 1493 to 38,407 Da. Acute pre-treatment with HPP1 or HPP2 (200 mg/kg, i.g.) could reduce mice’s immobility in behavioral despair tests, with HPP2 exhibiting superior efficacy. Additionally, both acute and sub-chronic pre-treatment with HPP2 (50, 200, and 800 mg/kg, i.g.) effectively alleviated depression-like symptoms in behavioral despair mice. Prolonged pre-treatment with HPP2 (200 mg/kg, i.g.) also mitigated the slow increase in body weight and behavioral abnormalities in foot-shock mice. Furthermore, HPP2 (200 mg/kg) successfully restored hippocampal histomorphological abnormalities, neurotrophic disturbance, and dysregulation of the gut microbiota in foot-shock mice. Conclusions: HPP2 exerts noteworthy antidepressant-like and anti-PTSD-like impact in mouse models via multiple targets, indicating a potential therapeutic candidate in depression and PTSD therapy. Full article
(This article belongs to the Special Issue Bioactive Ingredients in Plants Related to Human Health—2nd Edition)
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12 pages, 284 KB  
Article
Sacred Ambition, Secular Power: Jesuit Missions and the Rebalancing Authority of the Portuguese Empire, 1540–1759
by Boyu Fang
Religions 2025, 16(9), 1211; https://doi.org/10.3390/rel16091211 - 21 Sep 2025
Viewed by 1264
Abstract
This article treats the familiar triad “Gold, God, and Glory” as a heuristic to track how commercial, missionary, and reputational aims were configured within overlapping jurisdictions of the Portuguese world. Through three cases—the 1552 clash in Malacca between St. Francis Xavier and Captain [...] Read more.
This article treats the familiar triad “Gold, God, and Glory” as a heuristic to track how commercial, missionary, and reputational aims were configured within overlapping jurisdictions of the Portuguese world. Through three cases—the 1552 clash in Malacca between St. Francis Xavier and Captain D. Álvaro de Ataíde da Gama; the Gama family’s bargaining over offices and revenues; and the 1759 expulsion of the Society of Jesus—it argues that localized, negotiable frictions in the sixteenth century evolved into a structural confrontation by the mid-eighteenth century. Drawing on published Jesuit correspondence and secondary analyses of royal and municipal records, the study shows how missions initially supported metropolitan aims yet increasingly challenged them as Jesuit educational networks and revenue-bearing assets expanded. The Malacca dispute is read as a jurisdictional struggle over diplomatic access and rents, not merely a moral drama. The 1750 Treaty of Madrid and the Guaraní War further politicized perceptions of Jesuit wealth and influence, while the Lisbon-centered reform agenda after 1755 turned tension into rupture. Full article
(This article belongs to the Special Issue Religion, Mobility, and Transnational History)
14 pages, 1107 KB  
Article
B-Cell ST6Gal1/Neuraminidase 1 Ratios Inversely Predict the Combined Remission and Low-Disease-Activity Subgroup with DAS28-MCP-1 and SDAI Scores for Rheumatoid Arthritis
by Lieh-Bang Liou, Ping-Han Tsai, Yao-Fan Fang, Yen-Fu Chen, Che-Tzu Chang, Chih-Chieh Chen and Wen-Yu Chiang
Int. J. Mol. Sci. 2025, 26(17), 8226; https://doi.org/10.3390/ijms26178226 - 25 Aug 2025
Viewed by 879
Abstract
The associations between sialylated anti-cyclic citrullinated peptide (anti-CCP) antibodies bearing α-2,6-sialic acid (SIA), ST6Gal1 and Neu1 enzymes, and clinical disease activity measures such as disease activity score 28 (DAS28), the Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) are unknown [...] Read more.
The associations between sialylated anti-cyclic citrullinated peptide (anti-CCP) antibodies bearing α-2,6-sialic acid (SIA), ST6Gal1 and Neu1 enzymes, and clinical disease activity measures such as disease activity score 28 (DAS28), the Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) are unknown in rheumatoid arthritis (RA). To address this gap, this study included 97 patients with RA evaluated at baseline (month 0) and at 6 and 12 months. At each visit, blood cells were analyzed for B-cell ST6Gal1 and Neu1 expressions, and plasma samples were assessed for ST6Gal1 and Neu1 levels. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), and IgG anti-CCP with its α-2,6-SIA modification were measured. Disease activity measures, namely DAS28-ESR, DAS28-CRP, DAS28-MCP-1, SDAI, and CDAI, were calculated. Correlations and Receiver Operating Characteristics among ST6Gal, Neu1, SIA/anti-CCP ratios, and disease activity measures were assessed. Multivariate regression analyses were performed to reveal confounding factors in such correlations. The total SIA content of anti-CCP antibodies was inversely correlated with B-cell Neu1 levels (ρ = −0.317 with p = 0.013. Plasma (free-form) Neu1 levels were inversely correlated with SIA/IgG anti-CCP ratios (ρ = −0.361, p = 0.001) in the DAS28-MCP-1 < 2.2 (remission) subgroup. No such correlation was observed for the DAS28-ESR, DAS28-CRP, SDAI, or CDAI subgroups. B-cell ST6Gal1 levels correlated inversely with SDAI ≤ 11 and DAS28-MCP-1 ≤ 3.6 combined remission and low-disease-activity subgroups (ρ = −0.315 with p = 0.001 and ρ = −0.237 with p = 0.008, respectively). The same was observed for B-cell ST6Gal1/Neu1 ratios correlating with the SDAI ≤ 11 subgroup (ρ = −0.261, p = 0.009). Nevertheless, B-cell ST6Gal1/Neu1 ratios against SDAI ≤ 11 and DAS28-MCP-1 ≤ 3.6 subgroups produced significant area-under-curve (AUC) values of 0.616 and 0.600, respectively (asymptotic p-Values 0.004 and 0.018, respectively). Through multivariate regression analyses, we found that biologics (a confounding factor) interfered with p-Values related to the B-cell ST6Gal1 enzyme but did not interfere with p-Values related to the pure B-cell Neu1 enzyme. In addition, disease duration interfered with p-Values related to the pure Neu1 enzyme on B-cells or in plasma. Moreover, plasma ST6Gal1/Neu1 ratios against the DAS28-MCP-1 < 2.2 remission subgroup produced an AUC of 0.628 and asymptotic p = 0.003. Therefore, it is suggested that B-cell ST6Gal1/Neu1 ratios can be used as clinical indicators for the combined remission and low-disease-activity subgroup of SDAI and DAS28-MCP-1 formulae. Plasma ST6Gal1/Neu1 ratios are also good indicators of DAS28-MCP-1 remission. Full article
(This article belongs to the Section Biochemistry)
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18 pages, 3154 KB  
Article
Hyaluronic-Acid-Coated Sterosome for Dasatinib Delivery in Hepatocellular Carcinoma: Preparation, Physicochemical Characterization, and In Vitro Evaluation
by Chae Yeong Lee, Jeong Min Lee, Chung-Sung Lee and Hee Sook Hwang
Biomimetics 2025, 10(8), 552; https://doi.org/10.3390/biomimetics10080552 - 21 Aug 2025
Viewed by 1000
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and treatment remains challenging due to high recurrence rates, resistance to chemotherapy, and severe side effects. Dasatinib (Das) has shown therapeutic potential against HCC, but its clinical use is limited by poor [...] Read more.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and treatment remains challenging due to high recurrence rates, resistance to chemotherapy, and severe side effects. Dasatinib (Das) has shown therapeutic potential against HCC, but its clinical use is limited by poor bioavailability and short half-life (~3–4 h). Here, we developed a hyaluronic acid (HA)-coated sterosome for targeted and sustained delivery of Das to CD44-overexpressing HCC cells. Sterosomes composed of octadecylamine and cholesterol at a 5:5 (v/v) ratio were prepared via thin-film hydration and sonication, yielding stable particles (~90 nm) with high encapsulation efficiency (EE ~72%) for uncoated vesicles and ~58% after HA coating. HA-sterosomes (HA-St-Das) exhibited a uniform size (≈200 nm) and negative surface charge (–26 mV), with improved storage stability and resistance to lyophilization. In vitro release studies demonstrated pH-responsive Das release accelerated under acidic conditions (pH 6.0–5.0), mimicking tumor and lysosomal environments. In HepG2 cells, HA-St-Das exhibited enhanced cytotoxicity (IC50 ~7.0 μM) and prolonged intracellular retention compared to free Das and uncoated carriers. Fluorescence microscopy confirmed receptor-mediated uptake via CD44, leading to gradual and sustained intracellular delivery. Overall, the HA-St-Das system provides biocompatible, targeted, and controlled Das delivery, addressing key limitations of current liver cancer therapies and representing a promising nanomedicine platform for further development. Full article
(This article belongs to the Section Biomimetic Processing and Molecular Biomimetics)
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19 pages, 1080 KB  
Article
Microplastic Bioaccumulation and Oxidative Stress in Key Species of the Bulgarian Black Sea: Ecosystem Risk Early Warning
by Albena Alexandrova, Svetlana Mihova, Elina Tsvetanova, Madlena Andreeva, Georgi Pramatarov, Georgi Petrov, Nesho Chipev, Valentina Doncheva, Kremena Stefanova, Maria Grandova, Hristiyana Stamatova, Elitsa Hineva, Dimitar Dimitrov, Violin Raykov and Petya Ivanova
Microplastics 2025, 4(3), 50; https://doi.org/10.3390/microplastics4030050 - 6 Aug 2025
Cited by 1 | Viewed by 2203
Abstract
Plastic pollution in marine environments poses a new global threat. Microplastics (MPs) can bioaccumulate in marine organisms, leading to oxidative stress (OS). This study investigates MP accumulation and associated OS responses in six invertebrate species (Bivalvia, Gastropoda, and Malacostraca) and three key fish [...] Read more.
Plastic pollution in marine environments poses a new global threat. Microplastics (MPs) can bioaccumulate in marine organisms, leading to oxidative stress (OS). This study investigates MP accumulation and associated OS responses in six invertebrate species (Bivalvia, Gastropoda, and Malacostraca) and three key fish species of the Bulgarian Black Sea ecosystems. The target hydrobionts were collected from nine representative coastal habitats of the northern and southern aquatory. MPs were quantified microscopically, and OS biomarkers (lipid peroxidation, glutathione, and antioxidant enzymes) were analyzed spectrometrically in fish liver and gills and invertebrate soft tissues (STs). The specific OS (SOS) index was calculated as a composite indicator of the ecological impact, incl. MP effects. The results revealed species-specific MP bioaccumulation, with the highest concentrations in Palaemon adspersus, Rathke (1837) (0.99 ± 1.09 particles/g ST) and the least abundance in Bittium reticulatum (da Costa, 1778) (0.0033 ± 0.0025 particles/g ST). In Sprattus sprattus (Linnaeus, 1758), the highest accumulation of MPs was present (2.01 ± 2.56 particles/g muscle). The correlation analyses demonstrated a significant association between MP counts and catalase activity in all examined species. The SOS index varied among species, reflecting different stress responses, and this indicated that OS levels were linked to ecological conditions of the habitat and the species-specific antioxidant defense potential to overcome multiple stressors. These findings confirmed the importance of environmental conditions, including MP pollution and the evolutionarily developed capacity of marine organisms to tolerate and adapt to environmental stress. This study emphasizes the need for novel approaches in monitoring MPs and OS to better assess potential ecological risks. Full article
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13 pages, 1548 KB  
Article
Application of the Brillouin Optical Scanning System in the Regional Corneal Biomechanical Evaluation of Keratoconus and Its Correlation with Corvis ST Parameters
by Qiuruo Jiang, Yichen Sun, Zhanhao Gu, Lumeng Wang, Yiqiang Wu, Jialu Chen, Zhiyi Chen, Xiaobo Zheng and Shihao Chen
Bioengineering 2025, 12(6), 634; https://doi.org/10.3390/bioengineering12060634 - 11 Jun 2025
Viewed by 1551
Abstract
(1) Background: The early diagnosis of keratoconus is critical for prognosis. Traditional methods like ORA and Corvis ST measure overall corneal biomechanics but lack regional specificity and are affected by intraocular pressure. In contrast, Brillouin microscopy assesses regional corneal biomechanics without such limitations; [...] Read more.
(1) Background: The early diagnosis of keratoconus is critical for prognosis. Traditional methods like ORA and Corvis ST measure overall corneal biomechanics but lack regional specificity and are affected by intraocular pressure. In contrast, Brillouin microscopy assesses regional corneal biomechanics without such limitations; (2) Methods: In total, 25 keratoconus patients and 28 healthy controls were included in this study. Corneal biomechanics were measured using the BOSS system (Brillouin Optical Scanning System) in a 10-point mode within an 8 mm diameter, and included the mean, maximum, minimum and standard Brillouin shift. The Corvis ST parameters extracted included the CBI (Corneal Biomechanical Index), CCBI (Corvis Biomechanical Index for Chinese populations), SSI (Stress–Strain Index), DA (Deformation Amplitude), IIR (Inverse Integrated Radius), and SP-A1 (Stiffness Parameter at First Applanation); (3) Results: BOSS showed significant differences in the inferior nasal region (p = 0.004) and central region (p = 0.029) between groups, but not in peripheral regions (p = 0.781). In a comparison of the Brillouin frequency shifts measured between groups, there was no difference in the Mean (p = 0.452) and Max (p = 0.487), but the Min (p = 0.003), Standard (p = 0.000), and Max–Min (p = 0.006) all showed differences. Corvis ST identified significant differences in six parameters (CBI, CCBI, SSI, DA, IIR, and SP-A1) between groups (p < 0.001). Correlations were found between the BOSS and Corvis ST results, with moderate correlations in the inferior nasal region; (4) Conclusions: The BOSS Brillouin microscope can provide an accurate diagnostic evaluation for the corneal biomechanical differences between normal eyes and keratoconus, independent of IOP (Intraocular Pressure) and CCT (Central Corneal Thickness), with a good correlation with Corvis ST, especially in assessing regional biomechanics. Full article
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35 pages, 21941 KB  
Article
Explore the Ultra-High Density Urban Waterfront Space Form: An Investigation of Macau Peninsula Pier District via Point of Interest (POI) and Space Syntax
by Yue Huang, Yile Chen, Junxin Song, Liang Zheng, Shuai Yang, Yike Gao, Rongyao Li and Lu Huang
Buildings 2025, 15(10), 1735; https://doi.org/10.3390/buildings15101735 - 20 May 2025
Cited by 2 | Viewed by 2679
Abstract
High-density cities have obvious characteristics of compact urban spatial form and intensive land use in terms of spatial environment, and have always been a topic of academic focus. As a typical coastal historical district, the Macau Peninsula pier district (mainly the Macau Inner [...] Read more.
High-density cities have obvious characteristics of compact urban spatial form and intensive land use in terms of spatial environment, and have always been a topic of academic focus. As a typical coastal historical district, the Macau Peninsula pier district (mainly the Macau Inner Harbour) has a high building density and a low average street width, forming a vertical coastline development model that directly converses with the ocean. This area is adjacent to Macau’s World Heritage Site and directly related to the Marine trade functions. The distribution pattern of cultural heritage linked by the ocean has strengthened Macau’s unique positioning as a node city on the Maritime Silk Road. This text is based on the theory of urban development, integrates spatial syntax and POI analysis techniques, and combines the theories of waterfront regeneration, high-density urban form and post-industrial urbanism to integrate and deepen the theoretical framework, and conduct a systematic study on the urban spatial characteristics of the coastal area of the Macau Peninsula. This study found that (1) Catering and shopping facilities present a dual agglomeration mechanism of “tourism-driven + commercial core”, with Avenida de Almeida Ribeiro as the main axis and radiating to the Ruins of St. Paul’s and Praça de Ponte e Horta, respectively. Historical blocks and tourist hotspots clearly guide the spatial center of gravity. (2) Residential and life service facilities are highly coupled, reflecting the spatial logic of “work-residence integration-service coordination”. The distribution of life service facilities basically overlaps with the high-density residential area, forming an obvious “living circle + community unit” structure with clear spatial boundaries. (3) Commercial and transportation facilities form a “functional axis belt” organizational structure along the main road, with the Rua das Lorchas—Rua do Almirante Sérgio axis as the skeleton, constructing a “functional transmission chain”. (4) The spatial system of the Macau Peninsula pier district has transformed from a single center to a multi-node, network-linked structure. Its internal spatial differentiation is not only constrained by traditional land use functions but is also driven by complex factors such as tourism economy, residential migration, historical protection, and infrastructure accessibility. (5) Through the analysis of space syntax, it is found that the core integration of the Macau Peninsula pier district is concentrated near Pier 16 and the northern area. The two main roads have good accessibility for motor vehicle travel, and the northern area of the Macau Peninsula pier district has good accessibility for long and short-distance walking. Full article
(This article belongs to the Special Issue Digital Management in Architectural Projects and Urban Environment)
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15 pages, 3178 KB  
Article
Comparative Analysis of Chilling Injury in Banana Fruit During Storage: Physicochemical and Microstructural Changes, and Early Optical-Based Nondestructive Identification
by Hui Ma, Lingmeng Hu, Jingyuan Zhao, Jie He, Anqi Wen, Daizhu Lv, Zhi Xu, Weijie Lan and Leiqing Pan
Foods 2025, 14(8), 1319; https://doi.org/10.3390/foods14081319 - 11 Apr 2025
Cited by 1 | Viewed by 3320
Abstract
Chilling injury (CI) during postharvest storage seriously impairs bananas’ quality and marketability. This study systematically investigated CI mechanisms through physicochemical, microstructural, and optical analyses and innovatively developed a hyperspectral imaging (HSI)-based approach for early CI detection. Bananas stored at suboptimal (7 °C) and [...] Read more.
Chilling injury (CI) during postharvest storage seriously impairs bananas’ quality and marketability. This study systematically investigated CI mechanisms through physicochemical, microstructural, and optical analyses and innovatively developed a hyperspectral imaging (HSI)-based approach for early CI detection. Bananas stored at suboptimal (7 °C) and optimal (13 °C) conditions exhibited distinct physicochemical changes. CI progression was related to increased browning symptoms, an abnormal moisture redistribution (reduced pulp moisture content), and delayed softening. Microstructural analysis revealed membrane destabilization, cellular lysis, intercellular cavity formation, and inhibited starch hydrolysis under chilling stress. Hyperspectral microscope imaging (HMI) captured chilling-induced spectral variations (400–1000 nm), enabling the t-SNE-based clustering of CI-affected tissues. Machine learning models using first derivative (1-st)-processed spectra achieved a high accuracy. Both PLS-DA and RF had a 99% calibration accuracy and 98.5% prediction accuracy for CI classification. Notably, HSI detected spectral signatures of early CI (2 days post-chilling treatment) before visible symptoms, achieving a 100% identification accuracy with an optimized PLS-DA combined with 1-st processing. This study provides a theoretical basis for studying fruit CI mechanisms and a novel nondestructive optical method for early CI monitoring in postharvest supply chains. Full article
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15 pages, 1038 KB  
Article
Talented but Not Chosen—A Cross-Sectional Study—Do Coaches Release Late-Maturing Under-14 Players When Making Decisions?
by Fabiana Parreira Bonito, Júlia Teles, Tiago Matos, Filipe Jesus, Anna Volossovitch, Carlos Barrigas and Maria Isabel Fragoso
J. Funct. Morphol. Kinesiol. 2025, 10(2), 127; https://doi.org/10.3390/jfmk10020127 - 10 Apr 2025
Cited by 1 | Viewed by 1828
Abstract
Background: This cross-sectional study aims to clarify the relationship between coaches’ decisions and players’ relative age, biological maturation, and experience when identifying Under-14 (U14) players for the District and National Teams. Methods: A total of 360 male soccer players participating in [...] Read more.
Background: This cross-sectional study aims to clarify the relationship between coaches’ decisions and players’ relative age, biological maturation, and experience when identifying Under-14 (U14) players for the District and National Teams. Methods: A total of 360 male soccer players participating in the U14 national inter-association tournament, Lopes da Silva, were assessed. Birth dates were recorded, and players were categorized by birth quarter. Anthropometric measurements, fitness level (handgrip strength), and success indicators (performance evaluated by the coach, minutes played, and selection for the National Team) were documented, Maturation status was determined using bone age. Results: The majority of the sample was born in the 1st and 2nd quartiles regardless of maturation status. Morphological and functional differences between players born in different quartiles were no longer significant after controlling the effect of bone age. Late-maturing athletes played significantly fewer minutes. Among the players selected for the National Team, 89.9% were early or on-time maturers, and 92.9% were born in the first or second quartile of the year. While previous studies have shown reduced variability between bone and decimal age in the third and fourth quartiles, our findings indicate greater variability across all birth quartiles. Conclusions: Maturation status and relative age effect are crucial factors influencing coaches’ selection decisions. These findings highlight the need for a more equitable approach to talent identification, which should include track maturation bias avoiding the pursuit of short-term success and promoting long-term development programs for young soccer players. Undoubtedly, maturation status and relative age effect (RAE) play a significant role in a coach’s decision-making process. Full article
(This article belongs to the Section Athletic Training and Human Performance)
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32 pages, 820 KB  
Systematic Review
The Implementation of Shared Decision-Making Using Patient Decision Aid Tools to Select Breast Cancer Treatment Options: A Systematic Review in the Time of Minimum Quality Standards
by Olatz Lopez-Fernandez, Carmen P. Aguilar Castillo, Bárbara Horrillo, María Luisa Sánchez de Molina Ramperez and Héctor Guadalajara
Healthcare 2025, 13(7), 748; https://doi.org/10.3390/healthcare13070748 - 27 Mar 2025
Cited by 2 | Viewed by 2868
Abstract
Background: Research on shared decision making (SDM) has significantly increased in the 21st century. This study aims to review publications that include patient decision aid (PtDA) tools for selecting medical treatments for breast cancer (BC) since the advent of the minimum International [...] Read more.
Background: Research on shared decision making (SDM) has significantly increased in the 21st century. This study aims to review publications that include patient decision aid (PtDA) tools for selecting medical treatments for breast cancer (BC) since the advent of the minimum International Patient Decision Aid Standards (IPDAS) quality criteria. Methods: A systematic review was conducted using the PRISMA statement and focused on the literature published between 2013 and 2024. The databases included PubMed, Google Scholar, and PsycINFO. The quality of the studies was critically assessed. Results: A total of 29 empirical studies were examined, involving research conducted in Europe, America, and Asia. Most of the studies were quantitative clinical experiments, although qualitative and mixed methods were also reviewed. Three key themes were extracted: (1) study characteristics, including countries, sample sizes, and methodologies; (2) the clinical characterises and outcomes of the SDM processes and the implementation of PtDA tools; and (3) the various versions of the IPDAS criteria utilised. Conclusions: The medical option currently proposed includes a range of treatments, both surgical and nonsurgical options. Evidence shows positive outcomes associated with this healthcare approach; however, only half of the studies assessed utilised tools that met IPDAS criteria. Challenges remain in integrating SDM and PtDA tools into routine clinical practice, yet risk factors and potential solutions have been identified. Full article
(This article belongs to the Section Healthcare Quality, Patient Safety, and Self-care Management)
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