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18 pages, 5589 KB  
Article
Integrated Investigation Approach for Solid Waste Landfill Hazards—A Case Study of Two Decommissioned Industrial Sites
by Xiaoyu Zhang, Aijing Yin, Yuanyuan Lu, Zhewei Hu, Li Sun, Wenbing Ji, Qi Li, Caiyi Zhao, Yanhong Feng, Lingya Kong and Rongrong Ying
Toxics 2025, 13(10), 807; https://doi.org/10.3390/toxics13100807 - 23 Sep 2025
Viewed by 51
Abstract
Historical chemical production sites often harbor irregularly distributed solid waste landfills, posing significant environmental risks. Traditional drilling methods, while accurate, are inefficient for comprehensive characterization due to high costs and spatial limitations. This study aims to develop an integrated geophysical drilling approach to [...] Read more.
Historical chemical production sites often harbor irregularly distributed solid waste landfills, posing significant environmental risks. Traditional drilling methods, while accurate, are inefficient for comprehensive characterization due to high costs and spatial limitations. This study aims to develop an integrated geophysical drilling approach to accurately delineate the spatial distribution and volume of landfilled solid waste (predominantly organic pollutants) at two decommissioned chemical plant sites (total area: 8954 m2). Methods: We combined (1) geophysical surveys (transient electromagnetic (TEM, 50 profiles, 2936 points), high-density resistivity (HDR, 2 profiles, 192 points), and ground-penetrating radar (GPR, 22 profiles, 1072.1 m)) and (2) systematic drilling verification (136 boreholes, ≤10 m × 10 m density). Anomalies were interpreted through integrating geophysical responses, historical records, and borehole validation. Spatial modeling was conducted using Kriging interpolation in EVS software. The results show that (1) the anomalies exhibited a “sparse multi-point distribution” across zones A2 (primary waste concentration), A4, and A6, which were differentiated into solid waste, foundations, contaminated soil, voids, and cracks; (2) drilling confirmed solid waste at nine locations (A2: “multi-point, small-quantity” residues; A6: contaminated clay layers with garbage) with irregular thicknesses (0.2–1.3 m); (3) TEM identified diagnostic medium–high-resistivity anomalies (e.g., 28–37 m in A4L3), while GPR detected 17 shallow anomalies (only one validated as waste); and (4) the total waste volume was quantified as 266.9 m3. The methodology reduced the field effort by ∼35% versus drilling-only approaches, resolved geophysical limitations (e.g., HDR’s volume effect overestimating the thickness), and provided a validated framework for efficient characterization of complex historical landfills. Full article
(This article belongs to the Special Issue Novel Remediation Strategies for Soil Pollution)
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23 pages, 2240 KB  
Article
Multi-Modal Profiling Reveals Contrasting Immunomodulatory Effects of Recreational Marijuana Used Alone or with Tobacco in Youth with HIV
by Samiksha A. Borkar, Guglielmo M. Venturi, Kai-Fen Chang, Jingwen Gu, Li Yin, Jerry Shen, Bernard M. Fischer, Upasana Nepal, Isaac D. Raplee, Julie J. Kim-Chang, David M. Murdoch, Sharon L. Nichols, Lisa B. Hightow-Weidman, Charurut Somboonwit, John W. Sleasman and Maureen M. Goodenow
Cells 2025, 14(16), 1267; https://doi.org/10.3390/cells14161267 - 16 Aug 2025
Viewed by 798
Abstract
The evolving legal landscape has increased marijuana accessibility across the United States, including for medical use to manage clinical symptoms among people with HIV. The effects of marijuana use remain understudied in youth with HIV (YWH), who face lifelong antiretroviral therapy (ART) and [...] Read more.
The evolving legal landscape has increased marijuana accessibility across the United States, including for medical use to manage clinical symptoms among people with HIV. The effects of marijuana use remain understudied in youth with HIV (YWH), who face lifelong antiretroviral therapy (ART) and an elevated risk of developing comorbidities. This study applied a multi-modal approach, including plasma biomarker analysis, peripheral blood cell phenotyping, and transcriptome profiling, to examine the effects of recreational marijuana alone, tobacco alone, or marijuana combined with tobacco in virally suppressed YWH (≤50 RNA copies/mL) on ART compared to youth without HIV and YWH who used no substance. Marijuana use alone was associated with elevated IL-10 levels and normalization of pro-inflammatory genes and pathways, suggesting an immunomodulatory effect. Conversely, tobacco use alone or combined with marijuana was linked to increased IL-1β levels and heightened pro-inflammatory responses, including upregulation of genes involved in inflammasome activation. This study is the first to demonstrate GPR15 upregulation and potential marijuana-associated epigenetic modulation in HIV-suppressed youth. The findings identify potential markers for early detection of inflammation-related comorbidities in YWH, particularly among those exposed to tobacco and underscore the need for targeted profiling to guide personalized monitoring and early substance use intervention strategies for YWH. Full article
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19 pages, 6853 KB  
Article
Metabolomic and Molecular Mechanisms of Glycerol Supplementation in Regulating the Reproductive Function of Kazakh Ewes in the Non-Breeding Season
by Ying Nan, Baihui Jiang, Xingdong Qi, Cuifang Ye, Mengting Xie and Zongsheng Zhao
Animals 2025, 15(15), 2291; https://doi.org/10.3390/ani15152291 - 5 Aug 2025
Viewed by 410
Abstract
The activation mechanism of the reproductive axis in Kazakh ewes during the non-breeding season was explored by supplementation with glycerol complex (7% glycerol + tyrosine + vitamin B9). The experiment divided 50 ewes into five groups (n = 10). After 90 days [...] Read more.
The activation mechanism of the reproductive axis in Kazakh ewes during the non-breeding season was explored by supplementation with glycerol complex (7% glycerol + tyrosine + vitamin B9). The experiment divided 50 ewes into five groups (n = 10). After 90 days of intervention, it was found that significant changes in serum DL-carnitine, N-methyl-lysine and other differential metabolites were observed in the GLY-Tyr-B9 group (p < 0.05, “p < 0.05” means significant difference, “p < 0.01” means “highly significant difference”). The bile acid metabolic pathway was specifically activated (p < 0.01). The group had a 50% estrus rate, ovaries contained 3–5 immature follicles, and HE staining showed intact granulosa cell structure. Serum E2/P4 fluctuated cyclically (p < 0.01), FSH/LH pulse frequency increased (p < 0.01), peak Glu/INS appeared on day 60 (p < 0.05), and LEP was negatively correlated with body fat percentage (p < 0.01). Molecular mechanisms revealed: upregulation of hypothalamic kiss-1/GPR54 expression (p < 0.01) drove GnRH pulses; ovarian CYP11A1/LHR/VEGF synergistically promoted follicular development (p < 0.05); the HSL of subcutaneous fat was significantly increased (p < 0.05), suggesting involvement of lipolytic supply. Glycerol activates the reproductive axis through a dual pathway—L-carnitine-mediated elevation of mitochondrial β-oxidation efficacy synergizes with kisspeptin/GPR54 signalling enhancement to re-establish HPO axis rhythms. This study reveals the central role of metabolic reprogramming in regulating seasonal reproduction in ruminants. Full article
(This article belongs to the Section Small Ruminants)
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16 pages, 3538 KB  
Article
The Therapeutic Effect of GPR81 in Autoimmune Hepatitis and Hepatocellular Carcinoma via Regulating the Immune Response
by Yongmei Wu, Wenqian Song, Xuxian Wu, Jing He, Min Su, Rong Hu and Youbo Zhao
Int. J. Mol. Sci. 2025, 26(13), 6308; https://doi.org/10.3390/ijms26136308 - 30 Jun 2025
Viewed by 888
Abstract
Autoimmune hepatitis (AIH) is linked to an increased risk of hepatocellular carcinoma (HCC). However, the precise connection between the two remains unclear. GPR81, a G-protein-coupled receptor located on the membranes of various cell types, plays a role in numerous physiological processes. We established [...] Read more.
Autoimmune hepatitis (AIH) is linked to an increased risk of hepatocellular carcinoma (HCC). However, the precise connection between the two remains unclear. GPR81, a G-protein-coupled receptor located on the membranes of various cell types, plays a role in numerous physiological processes. We established an AIH animal model and activated GPR81 using the agonist 3,5-dihydroxybenzoic acid (3,5-DHBA). Additionally, the effect of GPR81 inhibition on tumor and immune cell dynamics was examined using the HepG2, Hep3B, and Hepa1-6 cell lines with the antagonist 3-hydroxybutyric acid (3-OBA). Our results demonstrated that 3,5-DHBA treatment reduced T cell and pro-inflammatory cytokine secretion, while MDSC secretion increased, inhibiting Concanavalin A (Con A)-induced AIH. The inhibition of GPR81 by 3-OBA suppressed HCC cell proliferation and invasion, reduced tumor volume and weight, and downregulated PD-L1 expression. Furthermore, CTL and DC activity in the spleen and tumors increased, while MDSC activity decreased. This study confirms that GPR81 plays an important role in both inflammation and tumorigenesis, suggesting that GPR81 may serve as a bridge in the transformation of inflammation into cancer. Modulating GPR81 activity may provide a novel therapeutic strategy for hepatitis and cancer. Full article
(This article belongs to the Section Molecular Immunology)
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23 pages, 6273 KB  
Article
Dynamic Transcriptomic and Cellular Remodeling Underlie Cuprizone-Induced Demyelination and Endogenous Repair in the CNS
by Yantuanjin Ma, Tianyi Liu, Zhipeng Li, Wei Wei, Qiting Zhao and Shufen Wang
Antioxidants 2025, 14(6), 692; https://doi.org/10.3390/antiox14060692 - 6 Jun 2025
Viewed by 958
Abstract
Demyelination in the central nervous system (CNS) disrupts neuronal communication and promotes neurodegeneration. Despite the widespread use of cuprizone-induced demyelination models to study myelin injury and repair, the mechanisms underlying oligodendrocyte apoptosis and regeneration are poorly understood. This study investigated the dynamic cellular [...] Read more.
Demyelination in the central nervous system (CNS) disrupts neuronal communication and promotes neurodegeneration. Despite the widespread use of cuprizone-induced demyelination models to study myelin injury and repair, the mechanisms underlying oligodendrocyte apoptosis and regeneration are poorly understood. This study investigated the dynamic cellular and molecular changes that occur during demyelination and remyelination, with a focus on glial cell responses, blood-brain barrier (BBB) integrity, and neuroimmune interactions. C57BL/6J mice exposed to cuprizone exhibited weight loss, sensorimotor deficits, and cognitive decline, which were reversed during remyelination. Histological and immunofluorescence analyses revealed reduced myelin protein levels, including myelin basic protein (MBP) and myelin-associated glycoprotein (MAG), and decreased oligodendrocyte populations during demyelination, with recovery during repair. The BBB permeability increases during demyelination, is associated with the decreased expression of tight junction proteins (ZO-1, Occludin), and normalizes during remyelination. Single-cell RNA sequencing revealed dynamic shifts in glial cell populations and upregulated Psap-Gpr37l1 signaling. Neuroimmune activation and oxidative stress peak during demyelination, characterized by elevated ROS, MDA, and immune cell infiltration, followed by recovery. Transcriptomic profiling revealed key inflammatory pathways (JAK-STAT, NF-κB) and hub genes associated with demyelination and repair. These findings provide insights into myelin repair mechanisms and highlight potential therapeutic targets for treating demyelinating diseases. Full article
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21 pages, 37932 KB  
Article
Combined L-Band Polarimetric SAR and GPR Data to Develop Models for Leak Detection in the Water Pipeline Networks
by Yuyao Zhang, Hongliang Guan and Fuzhou Duan
Remote Sens. 2025, 17(8), 1386; https://doi.org/10.3390/rs17081386 - 14 Apr 2025
Viewed by 1573
Abstract
Water pipeline leak detection in a fast and accurate way is of much importance for water utility companies and the general public. At present, the rapid development of remote sensing and computer technologies makes it possible to detect water pipeline leaks on a [...] Read more.
Water pipeline leak detection in a fast and accurate way is of much importance for water utility companies and the general public. At present, the rapid development of remote sensing and computer technologies makes it possible to detect water pipeline leaks on a large scale efficiently and timely. The leakage will cause an increase in the water content and dielectric constant of the soil around the pipeline, so it is feasible to determine the leakage site by measuring the subsurface soil relative dielectric constant (SSRDC). In this paper, we combine the SAOCOM-1A L-band synthetic-aperture radar (SAR) and the ground-penetrating radar (GPR) data to develop regression models that predict the SSRDC values. The model features are selected with the Boruta wrapper algorithm based on the SAOCOM-1A images after pre-processing, and the SSRDC values at sampling locations within the research area are calculated with the reflected wave method based on the GPR data. We evaluate multiple linear regression (MLR), random forest (RF), and multi-layer perceptron neural network (MLPNN) models for their ability to predict the SSRDC values using the selected features. The experimental results show that the MLPNN model (R2 = 0.705, RMSE = 1.936, MAE = 1.664) can better estimate the SSRDC values. Further, in the main urban area of Tianjin, China, which has a large water pipeline system, the SSDRC values of the area are obtained with the best model, and the locations where the predicted SSDRC values exceeded a certain threshold were considered potential leak locations. The empirical results indicate an encouraging potential of the proposed method to locate the pipeline leaks. This will provide a new avenue for the monitoring and treatment of water pipeline leaks. Full article
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18 pages, 3452 KB  
Article
Proteomic Analysis Reveals That Dietary Supplementation with Fish Oil Enhances Lipid Metabolism and Improves Antioxidant Capacity in the Liver of Female Scatophagus argus
by Jingwei He, He Ma, Dongneng Jiang, Tuo Wang, Zhiyuan Li, Gang Shi, Yucong Hong, Chunhua Zhu and Guangli Li
Fishes 2025, 10(3), 128; https://doi.org/10.3390/fishes10030128 - 15 Mar 2025
Viewed by 931
Abstract
The impact of dietary lipid sources on nutrient metabolism and reproductive development is a critical focus in aquaculture broodstock nutrition. Previous studies have demonstrated that fish oil supplementation modulates the expression of genes involved in steroid hormone synthesis, glucose, and lipid metabolism promoting [...] Read more.
The impact of dietary lipid sources on nutrient metabolism and reproductive development is a critical focus in aquaculture broodstock nutrition. Previous studies have demonstrated that fish oil supplementation modulates the expression of genes involved in steroid hormone synthesis, glucose, and lipid metabolism promoting ovarian development in female Scatophagus argus (spotted scat). However, the effects of fish oil on hepatic function at the protein level remain poorly characterized. In this study, female S. argus were fed diets containing 8% fish oil (FO, experimental group) or 8% soybean oil (SO, control group) for 60 days. Comparative proteomic analysis of liver tissue identified significant differential protein expression between groups. The FO group exhibited upregulation of lipid metabolism-related proteins, including COMM domain-containing protein 1 (Commd1), tetraspanin 8 (Tspan8), myoglobin (Mb), transmembrane protein 41B (Tmem41b), stromal cell-derived factor 2-like protein 1 (Sdf2l1), and peroxisomal biogenesis factor 5 (Pex5). Additionally, glucose metabolism-associated proteins, such as Sdf2l1 and non-POU domain-containing octamer-binding protein (Nono), were elevated in the FO group. Moreover, proteins linked to inflammation and antioxidant responses, including G protein-coupled receptor 108 (Gpr108), protein tyrosine phosphatase non-receptor type 2 (Ptpn2), Pex5, p120 catenin (Ctnnd1), tripartite motif-containing protein 16 (Trim16), and aquaporin 11 (Aqp11), were elevated in the FO group, while proteins involved in oxidative stress, such as reactive oxygen species modulator 1 (Romo1), cathepsin A (Ctsa), and Cullin 4A (Cul4a), were downregulated. These proteomic findings align with prior transcriptomic data, indicating that dietary fish oil enhances hepatic lipid metabolism, mitigates oxidative stress, and strengthens antioxidant capacity. Furthermore, these hepatic adaptations may synergistically support ovarian maturation in S. argus. This study provides novel proteomic-level evidence supporting the role of fish oil in modulating hepatic lipid and energy metabolism, thereby elucidating the role of fish oil in optimizing hepatic energy metabolism and redox homeostasis to influence reproductive processes, advancing our understanding of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) in teleost liver physiology. Full article
(This article belongs to the Section Nutrition and Feeding)
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24 pages, 4172 KB  
Article
Data-Driven Identification of Early Cancer-Associated Genes via Penalized Trans-Dimensional Hidden Markov Models
by Saeedeh Hajebi Khaniki and Farhad Shokoohi
Biomolecules 2025, 15(2), 294; https://doi.org/10.3390/biom15020294 - 16 Feb 2025
Viewed by 875
Abstract
Colorectal cancer (CRC) is a significant worldwide health problem due to its high prevalence, mortality rates, and frequent diagnosis at advanced stages. While diagnostic and therapeutic approaches have evolved, the underlying mechanisms driving CRC initiation and progression are not yet fully understood. Early [...] Read more.
Colorectal cancer (CRC) is a significant worldwide health problem due to its high prevalence, mortality rates, and frequent diagnosis at advanced stages. While diagnostic and therapeutic approaches have evolved, the underlying mechanisms driving CRC initiation and progression are not yet fully understood. Early detection is critical for improving patient survival, as initial cancer stages often exhibit epigenetic changes—such as DNA methylation—that regulate gene expression and tumor progression. Identifying DNA methylation patterns and key survival-related genes in CRC could thus enhance diagnostic accuracy and extend patient lifespans. In this study, we apply two of our recently developed methods for identifying differential methylation and analyzing survival using a sparse, finite mixture of accelerated failure time regression models, focusing on key genes and pathways in CRC datasets. Our approach outperforms two other leading methods, yielding robust findings and identifying novel differentially methylated cytosines. We found that CRC patient survival time follows a two-component mixture regression model, where genes CDH11, EPB41L3, and DOCK2 are active in the more aggressive form of CRC, whereas TMEM215, PPP1R14A, GPR158, and NAPSB are active in the less aggressive form. Full article
(This article belongs to the Section Molecular Genetics)
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12 pages, 1110 KB  
Article
Cholesin mRNA Expression in Human Intestinal, Liver, and Adipose Tissues
by Hannah Gilliam-Vigh, Malte P. Suppli, Sebastian M. N. Heimbürger, Asger B. Lund, Filip K. Knop and Anne-Marie Ellegaard
Nutrients 2025, 17(4), 619; https://doi.org/10.3390/nu17040619 - 8 Feb 2025
Cited by 1 | Viewed by 1703
Abstract
Objective: Cholesin is a recently discovered gut-derived hormone secreted by enterocytes upon dietary cholesterol uptake via the transmembrane sterol transporter Niemann–Pick disease C1-like intracellular cholesterol transporter 1 (NPC1L1). In the liver, cholesin activates G protein-coupled receptor 146 (GPR146), causing reduced cholesterol synthesis. In [...] Read more.
Objective: Cholesin is a recently discovered gut-derived hormone secreted by enterocytes upon dietary cholesterol uptake via the transmembrane sterol transporter Niemann–Pick disease C1-like intracellular cholesterol transporter 1 (NPC1L1). In the liver, cholesin activates G protein-coupled receptor 146 (GPR146), causing reduced cholesterol synthesis. In this exploratory, hypothesis-generating study based on post hoc analysis, human data on the cholesin system are presented. Methods: Mucosal biopsies were collected throughout the intestinal tract from 12 individuals with type 2 diabetes (T2D) and 12 healthy, matched controls. Upper small intestinal mucosal biopsies were collected from 20 individuals before and after Roux-en-Y gastric bypass (RYGB) surgery. Liver biopsies were collected from 12 men with obesity and 15 matched controls without obesity. Subcutaneous abdominal adipose tissue biopsies were collected from 20 men with type 1 diabetes (T1D). All biopsies underwent full mRNA sequencing. Results: Cholesin mRNA expression was observed throughout the intestinal tracts of the individuals with T2D and the controls, in the livers of men with and without obesity, and in adipose tissue of men with T1D. NPC1L1 mRNA expression was robust throughout the small intestines but negligible in the large intestines of both individuals with and without T2D. RYGB surgery induced the expression of NPC1L1 mRNA in the upper small intestine. GPR146 mRNA was expressed in the livers of men, both with and without obesity, and in the adipose tissue of men with T1D, but not in the intestines. Conclusions: Our results suggest a role of the cholesin system in human physiology, but whether it is perturbed in metabolic diseases remains unknown. Clinical trial registration numbers: NCT03044860, NCT03093298, NCT02337660, NCT03734718. Full article
(This article belongs to the Special Issue Bioactive Lipids and Metabolic Disease)
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18 pages, 12913 KB  
Article
Soil Organic Carbon Estimation and Transfer Framework in Agricultural Areas Based on Spatiotemporal Constraint Strategy Combined with Active and Passive Remote Sensing
by Jiaxin Qian, Jie Yang, Weidong Sun, Lingli Zhao, Lei Shi, Hongtao Shi, Lu Liao, Chaoya Dang and Qi Dou
Remote Sens. 2025, 17(2), 333; https://doi.org/10.3390/rs17020333 - 19 Jan 2025
Viewed by 1303
Abstract
Mapping soil organic carbon (SOC) plays a crucial role in agricultural productivity and water management. This study discusses the potential of active and passive remote sensing for SOC estimation modeling in agricultural areas, incorporating synthetic aperture radar (SAR) data (L-band quad-polarization and C-band [...] Read more.
Mapping soil organic carbon (SOC) plays a crucial role in agricultural productivity and water management. This study discusses the potential of active and passive remote sensing for SOC estimation modeling in agricultural areas, incorporating synthetic aperture radar (SAR) data (L-band quad-polarization and C-band dual-polarization), multi-spectrum (MS) data, and brightness temperature (TB) data. The performance of five advanced machine learning regression (MLR) models for SOC modeling was assessed, focusing on spatial interpolation accuracy and cross-spatial transfer accuracy, using two field observation datasets for modeling and validation. Results indicate that the SOC estimation accuracy when using MS data alone is comparable to that of using TB data alone, and both perform slightly better than SAR data. Radar cross-polarization ratio index, microwave polarization difference index, shortwave infrared reflectance, and soil parameters (elevation and soil moisture) demonstrate high correlation with the measured SOC. Incorporating temporal features, as opposed to single-phase features, allows each regression model to reach its upper limit of SOC estimation accuracy. The spatial interpolation accuracy of each MLR algorithm is satisfactory, with the Gaussian process regression (GPR) model demonstrating optimal modeling performance. When SAR, MS, or TB data are used individually in modeling, the estimation errors (RMSE) for SOC are 0.637 g/kg, 0.492 g/kg, and 0.229 g/kg for the SMAPVEX12 sampling campaign, and 0.706 g/kg, 0.454 g/kg, and 0.474 g/kg for the SMAPVEX16-MB sampling campaign, respectively. After incorporating soil moisture and topographic factors, the above RMSEs for SOC are further reduced by 57.8%, 35.6%, and 3.5% for the SMAPVEX12, and by 18.4%, 8.8%, and 3.4% for the SMAPVEX16-MB, respectively. However, cross-spatial transfer accuracy of the regression models remains limited (RMSE = 0.866–1.043 g/kg and 0.995–1.679 g/kg for different data sources). To address this, this study reduces uncertainties in SOC cross-spatial transfer by introducing terrain factors sensitive to SOC (RMSE = 0.457–0.516 g/kg and 0.799–1.198 g/kg for different data sources). The proposed SOC estimation and transfer framework, based on active and passive remote sensing data, provides guidance for high-resolution regional-scale SOC mapping and applications. Full article
(This article belongs to the Special Issue Proximal and Remote Sensing for Low-Cost Soil Carbon Stock Estimation)
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21 pages, 3504 KB  
Article
G Protein-Coupled Receptor 17 Inhibits Glucagon-like Peptide-1 Secretion via a Gi/o-Dependent Mechanism in Enteroendocrine Cells
by Jason M. Conley, Alexander Jochim, Carmella Evans-Molina, Val J. Watts and Hongxia Ren
Biomolecules 2025, 15(1), 9; https://doi.org/10.3390/biom15010009 - 25 Dec 2024
Cited by 3 | Viewed by 5446
Abstract
Gut peptides, including glucagon-like peptide-1 (GLP-1), regulate metabolic homeostasis and have emerged as the basis for multiple state-of-the-art diabetes and obesity therapies. We previously showed that G protein-coupled receptor 17 (GPR17) is expressed in intestinal enteroendocrine cells (EECs) and modulates nutrient-induced GLP-1 secretion. [...] Read more.
Gut peptides, including glucagon-like peptide-1 (GLP-1), regulate metabolic homeostasis and have emerged as the basis for multiple state-of-the-art diabetes and obesity therapies. We previously showed that G protein-coupled receptor 17 (GPR17) is expressed in intestinal enteroendocrine cells (EECs) and modulates nutrient-induced GLP-1 secretion. However, the GPR17-mediated molecular signaling pathways in EECs have yet to be fully deciphered. Here, we expressed the human GPR17 long isoform (hGPR17L) in GLUTag cells, a murine EEC line, and we used the GPR17 synthetic agonist MDL29,951 together with pharmacological probes and genetic approaches to quantitatively assess the contribution of GPR17 signaling to GLP-1 secretion. Constitutive hGPR17L activity inhibited GLP-1 secretion, and MDL29,951 treatment further inhibited this secretion, which was attenuated by treatment with the GPR17 antagonist HAMI3379. MDL29,951 promoted both Gi/o and Gq protein coupling to mediate cyclic AMP (cAMP) and calcium signaling. hGPR17L regulation of GLP-1 secretion appeared to be Gq-independent and dependent upon Gi/o signaling, but was not correlated with MDL29,951-induced whole-cell cAMP signaling. Our studies revealed key signaling mechanisms underlying the role of GPR17 in regulating GLP-1 secretion and suggest future opportunities for pharmacologically targeting GPR17 with inverse agonists to maximize GLP-1 secretion. Full article
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30 pages, 6820 KB  
Article
Sustainable Photodegradation of Amoxicillin in Wastewater with a Nickel Aluminate and ZnO Heterosystem Oxides: Experimental and Gaussian Process Regression Modeling Studies
by Mohammed Kebir, Rachida Bouallouche, Noureddine Nasrallah, Hichem Tahraoui, Noureddine Elboughdiri, Farid Ait Merzeg, Fayçal Dergal, Saifi Amirouche, Aymen Amine Assadi, Abdeltif Amrane, Mohamed Trari and Jie Zhang
Catalysts 2024, 14(12), 875; https://doi.org/10.3390/catal14120875 - 29 Nov 2024
Cited by 8 | Viewed by 1414
Abstract
The wastewater generated by the pharmaceutical industry poses a risk to the environment due to undesirable characteristics such as low biodegradability, high levels of contaminants, and the presence of suspended solids, in addition to the high load of organic matter due to the [...] Read more.
The wastewater generated by the pharmaceutical industry poses a risk to the environment due to undesirable characteristics such as low biodegradability, high levels of contaminants, and the presence of suspended solids, in addition to the high load of organic matter due to the presence of drugs and other emerging products in the effluent. This study aims to reduce the impact of wastewater pollution by removing amoxicillin (AMO) antibiotics as an organic pollutant. In this concept, two synthesized catalysts, NiAl2O4 and ZnO, are sensitive oxides to light energy. The prepared materials were then characterized using X-ray diffraction, UV–vis solid reflectance diffuse, Raman spectroscopy, scanning electron microscopy, BET, and ATR-FTIR spectroscopy. The effects of principal operating parameters under sunlight, namely, the percentage of the mixture of NiAl2O4 and ZnO, the pH of the medium, and the initial concentration of the antibiotic were studied experimentally to determine the optimal conditions for achieving a high degradation rate. The results showed that photodegradation is higher at a pH of 6, with a weight percentage of the mixture of 50% for both catalysts in 1 g/L of the total catalyst dose. Then, the effect of the initial concentration of AMO on the photodegradation reaction showed an important influence on the photodegradation process; as the degradation rate decreases, the initial AMO concentration increases. A high degradation rate of 92% was obtained for an initial AMO concentration of 10 mg/L and a pH of 6. The kinetic study of degradation established that the first-order model and the Langmuir–Hinshelwood (LH) mechanism fit the experimental data perfectly. The study showed the success of using heterosystem photocatalysts and sustainable energy for effective pharmaceutical removal, which can be extended to treat wastewater with other organic emerging pollutants. On the other hand, modeling was introduced using Gaussian process regression (GPR) to predict the degradation rate of AMO under sunlight in the presence of heterogeneous ZnO and NiAl2O4 systems. The model evaluation criteria of GPR in terms of statistical coefficients and errors show very interesting results and the performance of the model used. Where statistical coefficients were close to one (R = 0.9981), statistical errors were very small (RMSE = 0.1943 and MAE = 0.0518). The results suggest that the model has a strong predictive power and can be used to optimize the process of AMO removal from wastewater. Full article
(This article belongs to the Section Photocatalysis)
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24 pages, 7281 KB  
Article
Pancreastatin Inhibition Alters the Colonic Epithelial Cells Profile in a Sex-Dependent Manner
by Diane M. Tshikudi, Hannah Hutchison and Jean-Eric Ghia
Int. J. Mol. Sci. 2024, 25(23), 12757; https://doi.org/10.3390/ijms252312757 - 27 Nov 2024
Viewed by 1144
Abstract
The impaired mucosal barrier is a hallmark of ulcerative colitis (UC), an inflammatory colonic disorder with epidemiological and pathophysiology sex bias. UC Patients overexpress the colonic epithelial cells (CECs)-derived peptide pancreastatin (PST). Pancreastatin inhibitor 8 (PSTi8), an inhibitor of PST, has shown promising [...] Read more.
The impaired mucosal barrier is a hallmark of ulcerative colitis (UC), an inflammatory colonic disorder with epidemiological and pathophysiology sex bias. UC Patients overexpress the colonic epithelial cells (CECs)-derived peptide pancreastatin (PST). Pancreastatin inhibitor 8 (PSTi8), an inhibitor of PST, has shown promising anti-inflammatory effects on UC. However, no data exist in the context of CEC barrier function and integrity. We investigated the impact of PSTi8 treatment on CECs in homeostatic and colitic conditions. PSTi8 (2.5 mg/mL/kg, i.r.) or PBS treatment started one day before colitis induction (5% dextran sodium sulfate for five days) in male and female C57BL/6 mice. The disease activity score was assessed daily. Epithelial-associated cytokines, markers specific to differentiation, proliferation, differentiated CECs, stem cells, CECs regulators, and the PSTi8 G-protein coupled receptor 78 (GPR78) signaling pathway, were evaluated using ELISA, immunofluorescence and qRT-PCR. PSTi8 treatment reduced the epithelial-associated cytokines and differentiated CECs while promoting CEC proliferation and self-renewal in females at a steady state through the GRP78 signaling pathway. PSTi8 treatment exacerbated colitis severity and increased CEC differentiation while reducing proliferation in colitic females. Conversely, PSTi8 treatment reduced males’ susceptibility to colitis by preserving stem cells and differentiated CECs. PST regulated colonic mucosal maintenance in a sex- and disease-dependent manner. Full article
(This article belongs to the Section Molecular Immunology)
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15 pages, 3522 KB  
Article
Resveratrol Butyrate Esters Reduce Hypertension in a Juvenile Rat Model of Chronic Kidney Disease Exacerbated by Microplastics
by Yi-Ning Huang, Chien-Ning Hsu, Chih-Yao Hou, Shin-Yu Chen and You-Lin Tain
Nutrients 2024, 16(23), 4076; https://doi.org/10.3390/nu16234076 - 27 Nov 2024
Cited by 4 | Viewed by 1662
Abstract
Background: Resveratrol is recognized as a promising nutraceutical with antihypertensive and prebiotic properties; however, its bioavailability in vivo is limited. To enhance its bioactivity, we developed resveratrol butyrate esters (RBEs). This study investigates whether RBEs can mitigate hypertension induced by chronic kidney disease [...] Read more.
Background: Resveratrol is recognized as a promising nutraceutical with antihypertensive and prebiotic properties; however, its bioavailability in vivo is limited. To enhance its bioactivity, we developed resveratrol butyrate esters (RBEs). This study investigates whether RBEs can mitigate hypertension induced by chronic kidney disease (CKD) and exacerbated by microplastics (MPs) exposure in juvenile rats. Methods: Three-week-old male Sprague Dawley rats were fed either regular chow or 0.5% adenine chow for three weeks. The adenine-fed CKD rats (N = 8 per group) received either 5 μM MPs (10 mg/L) or MPs combined with RBE (25 mg/L) in their drinking water from weeks 3 to 9. Results: Our results indicate that MP exposure worsened CKD-induced hypertension, while RBE treatment resulted in a reduction in systolic BP by 15 mmHg (155 ± 2 mmHg vs. 140 ± 1 mmHg, p < 0.05). The combined exposure to adenine and MPs was associated with nitric oxide (NO) deficiency, which RBE treatment alleviated. Additionally, our findings revealed that RBE modulated both the classical and nonclassical renin–angiotensin system (RAS), contributing to its protective effects. We also observed changes in gut microbiota composition, increased butyric acid levels, and elevated renal GPR41 expression associated with RBE treatment. Conclusions: In conclusion, in this juvenile rat model of combined CKD and MP exposure, RBE demonstrates antihypertensive effects by modulating NO levels, the RAS, gut microbiota, and their metabolites. Full article
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Article
Experimental Investigation and Machine Learning Modeling of Tribological Characteristics of AZ31/B4C/GNPs Hybrid Composites
by Dhanunjay Kumar Ammisetti, Bharat Kumar Chigilipalli, Baburao Gaddala, Ravi Kumar Kottala, Radhamanohar Aepuru, T. Srinivasa Rao, Seepana Praveenkumar and Ravinder Kumar
Crystals 2024, 14(12), 1007; https://doi.org/10.3390/cryst14121007 - 21 Nov 2024
Cited by 2 | Viewed by 1229
Abstract
In this study, the AZ31 hybrid composites reinforced with boron carbide (B4C) and graphene nano-platelets (GNPs) are prepared by the stir casting method. The main aim of the study is to study the effect of various wear parameters (reinforcement percentage (R), [...] Read more.
In this study, the AZ31 hybrid composites reinforced with boron carbide (B4C) and graphene nano-platelets (GNPs) are prepared by the stir casting method. The main aim of the study is to study the effect of various wear parameters (reinforcement percentage (R), applied load (L), sliding distance (D), and velocity (V)) on the wear characteristics (wear rate (WR)) of the AZ91/B4C/GNP composites. Experiments are designed using the Taguchi technique, and it was determined that load (L) is the most significant parameter affecting WR, followed by D, R, and V. The wear mechanisms under conditions of maximum and minimum wear rates are examined using SEM analysis of the worn-out surfaces of the specimens. From the result analysis on the WR, the ideal conditions for achieving the lowest WR are R = 4 wt.%, L = 15 N, V = 3 m/s, and D = 500 m. Machine learning (ML) models, including linear regression (LR), polynomial regression (PR), random forest (RF), and Gaussian process regression (GPR), are implemented to develop a reliable prediction model that forecasts output responses in accordance with input variables. A total of 90% of the experimental data points were used to train and 10% to evaluate the models. The PR model exceeded the accuracy of other models in predicting WR, with R2 = 0.953, MSE = 0.011, RMSE = 0.103, and COF with R2 = 0.937, MSE = 0.013, and RMSE = 0.114, respectively. Full article
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