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23 pages, 3521 KiB  
Article
Efficacy of NAMPT Inhibitors in Pancreatic Cancer After Stratification by MAP17 (PDZK1IP1) Levels
by Eva M. Verdugo-Sivianes, Julia Martínez-Pérez, Lola E Navas, Carmen Sáez and Amancio Carnero
Cancers 2025, 17(15), 2575; https://doi.org/10.3390/cancers17152575 - 5 Aug 2025
Abstract
Background/Objectives: Pancreatic cancer (PC) is the seventh leading cause of cancer-related deaths worldwide, with its incidence rising each year. Despite its relatively low incidence, the aggressiveness of pancreatic cancer results in high mortality, with only 12% of patients surviving five years post-diagnosis. [...] Read more.
Background/Objectives: Pancreatic cancer (PC) is the seventh leading cause of cancer-related deaths worldwide, with its incidence rising each year. Despite its relatively low incidence, the aggressiveness of pancreatic cancer results in high mortality, with only 12% of patients surviving five years post-diagnosis. Surgical resection remains the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage. The goal of this work is to identify vulnerabilities that can affect the efficacy of treatments and improve the efficacy of therapy. Methods: MAP17 overexpression in pancreatic cancer cell lines, RT-qPCR analysis, xenografts, in vitro and in vivo treatments, analysis of data from pancreatic tumors in transcriptomic patient databases. Results: We studied the prognostic and predictive value of MAP17 (PDZK1IP1) expression in pancreatic cancer, and we found that high MAP17 mRNA expression was associated with poor prognosis. In addition, single-cell analysis revealed that high MAP17 expression was present only in tumor cells. We investigated whether the response to various antitumor agents depended on MAP17 expression. In 2D culture, MAP17-expressing pancreatic cancer cells responded better to gemcitabine and 5-fluorouracil. However, in vivo xenograft tumors with MAP17 expression showed resistance to all treatments. Additionally, MAP17-expressing cells had a high NAD pool, which seems to be effectively depleted in vivo by NAMPT inhibitors, the primary enzyme for NAD biosynthesis. Conclusions: Our findings suggest that MAP17 expression could enhance the prognostic stratification of pancreatic cancer patients. Moreover, the coadministration of NAMPT inhibitors with current treatments may sensitize tumors with high MAP17 expression to chemotherapy and improve the efficacy of chemotherapy. Full article
(This article belongs to the Section Molecular Cancer Biology)
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17 pages, 6882 KiB  
Article
Development and Evaluation of a Solar Milk Pasteurizer for the Savanna Ecological Zones of West Africa
by Iddrisu Ibrahim, Paul Tengey, Kelci Mikayla Lawrence, Joseph Atia Ayariga, Fortune Akabanda, Grace Yawa Aduve, Junhuan Xu, Robertson K. Boakai, Olufemi S. Ajayi and James Owusu-Kwarteng
Solar 2025, 5(3), 38; https://doi.org/10.3390/solar5030038 - 4 Aug 2025
Abstract
In many developing African countries, milk safety is often managed through traditional methods such as fermentation or boiling over firewood. While these approaches reduce some microbial risks, they present critical limitations. Firewood dependency contributes to deforestation, depletion of agricultural residues, and loss of [...] Read more.
In many developing African countries, milk safety is often managed through traditional methods such as fermentation or boiling over firewood. While these approaches reduce some microbial risks, they present critical limitations. Firewood dependency contributes to deforestation, depletion of agricultural residues, and loss of soil fertility, which, in turn, compromise environmental health and food security. Solar pasteurization provides a reliable and sustainable method for thermally inactivating pathogenic microorganisms in milk and other perishable foods at sub-boiling temperatures, preserving its nutritional quality. This study aimed to evaluate the thermal and microbial performance of a low-cost solar milk pasteurization system, hypothesized to effectively reduce microbial contaminants and retain milk quality under natural sunlight. The system was constructed using locally available materials and tailored to the climatic conditions of the Savanna ecological zone in West Africa. A flat-plate glass solar collector was integrated with a 0.15 cm thick stainless steel cylindrical milk vat, featuring a 2.2 cm hot water jacket and 0.5 cm thick aluminum foil insulation. The system was tested in Navrongo, Ghana, under ambient temperatures ranging from 30 °C to 43 °C. The pasteurizer successfully processed up to 8 L of milk per batch, achieving a maximum milk temperature of 74 °C by 14:00 GMT. Microbial analysis revealed a significant reduction in bacterial load, from 6.6 × 106 CFU/mL to 1.0 × 102 CFU/mL, with complete elimination of coliforms. These results confirmed the device’s effectiveness in achieving safe pasteurization levels. The findings demonstrate that this locally built solar pasteurization system is a viable and cost-effective solution for improving milk safety in arid, electricity-limited regions. Its potential scalability also opens avenues for rural entrepreneurship in solar-powered food and water treatment technologies. Full article
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20 pages, 2424 KiB  
Article
Loss of SVIP Results in Metabolic Reprograming and Increased Retention of Very-Low-Density Lipoproteins in Hepatocytes
by Vandana Sekhar, Thomas Andl and Shadab A. Siddiqi
Int. J. Mol. Sci. 2025, 26(15), 7465; https://doi.org/10.3390/ijms26157465 - 1 Aug 2025
Viewed by 156
Abstract
Perturbations in the tightly regulated processes of VLDL biosynthesis and secretion can directly impact both liver and cardiovascular health. Patients with metabolic disorders have an increased risk of developing hepatic steatosis, which can lead to cirrhosis. These associated metabolic risks underscore the importance [...] Read more.
Perturbations in the tightly regulated processes of VLDL biosynthesis and secretion can directly impact both liver and cardiovascular health. Patients with metabolic disorders have an increased risk of developing hepatic steatosis, which can lead to cirrhosis. These associated metabolic risks underscore the importance of discerning the role of different cellular proteins involved in VLDL biogenesis, transport, and secretion. Small VCP-Interacting Protein (SVIP) has been identified as a component of VLDL transport vesicles and VLDL secretion. This study evaluates the cellular effects stemming from the CRISPR-Cas9-mediated depletion of SVIP in rat hepatocytes. The SVIP-knockout (KO) cells display an increased VLDL retention with elevated intracellular levels of ApoB100 and neutral lipid staining. RNA sequencing studies reveal an impaired PPARα and Nrf2 signaling in the SVIP KO cells, implying a state of metabolic reprograming, with a shift from fatty acid uptake, synthesis, and oxidation to cells favoring the activation of glucose by impaired glycogen storage and increased glucose release. Additionally, SVIP KO cells exhibit a transcriptional profile indicative of acute phase response (APR) in hepatocytes. Many inflammatory markers and genes associated with APR are upregulated in the SVIP KO hepatocytes. In accordance with an APR-like response, the cells also demonstrate an increase in mRNA expression of genes associated with protein synthesis. Together, our data demonstrate that SVIP is critical in maintaining hepatic lipid homeostasis and metabolic balance by regulating key pathways such as PPARα, Nrf2, and APR. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
20 pages, 6929 KiB  
Article
Protective Effects of Sodium Copper Chlorophyllin and/or Ascorbic Acid Against Barium Chloride-Induced Oxidative Stress in Mouse Brain and Liver
by Salma Benayad, Basma Es-Sai, Yassir Laaziouez, Soufiane Rabbaa, Hicham Wahnou, Habiba Bouchab, Hicham El Attar, Bouchra Benabdelkhalek, Loubna Amahdar, Oualid Abboussi, Raphaël Emmanuel Duval, Riad El Kebbaj and Youness Limami
Molecules 2025, 30(15), 3231; https://doi.org/10.3390/molecules30153231 - 1 Aug 2025
Viewed by 143
Abstract
Barium chloride (BaCl2), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl2-induced oxidative damage in [...] Read more.
Barium chloride (BaCl2), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl2-induced oxidative damage in the liver and brain of mice using a two-phase experimental protocol. Animals received either SCC (40 mg/kg), ASC (160 mg/kg), or their combination for 14 days prior to BaCl2 exposure (150 mg/L in drinking water for 7 days), allowing evaluation of both preventive and therapeutic effects. Toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. Body weight, liver and kidney indices, and biochemical markers (Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), creatinine) remained within physiological ranges, and no anxiogenic or locomotor effects were observed. In the brain, BaCl2 exposure significantly increased SOD (+49%), CAT (+66%), GPx (+24%), and GSH (+26%) compared to controls, reflecting a robust compensatory antioxidant response. Although lipid peroxidation (MDA) showed a non-significant increase, SCC, ASC, and their combination reduced MDA levels by 42%, 37%, and 55%, respectively. These treatments normalized antioxidant enzyme activities and GSH, indicating an effective neuroprotective effect. In contrast, the liver exhibited a different oxidative profile. BaCl2 exposure increased MDA levels by 80% and GSH by 34%, with no activation of SOD, CAT, or GPx. Histological analysis revealed extensive hepatocellular necrosis, vacuolization, and inflammatory infiltration. SCC significantly reduced hepatic MDA by 39% and preserved tissue architecture, while ASC alone or combined with SCC exacerbated inflammation and depleted hepatic GSH by 71% and 78%, respectively, relative to BaCl2-exposed controls. Collectively, these results highlight a differential, organ-specific response to BaCl2-induced oxidative stress and the therapeutic potential of SCC and ASC. SCC emerged as a safer and more effective agent, particularly in hepatic protection, while both antioxidants demonstrated neuroprotective effects when used individually or in combination. Full article
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15 pages, 5769 KiB  
Article
Higher Winter Precipitation and Temperature Are Associated with Smaller Earlywood Vessel Size but Wider Latewood Width in Quercus faginea Lam.
by Ignacio García-González, Filipe Campelo, Joana Vieira and Cristina Nabais
Forests 2025, 16(8), 1252; https://doi.org/10.3390/f16081252 - 1 Aug 2025
Viewed by 167
Abstract
Quercus faginea Lam., a winter-deciduous oak native to the Iberian Peninsula, typically grows under a Mediterranean climate. To identify the main drivers influencing radial wood increment, we analyzed the climatic signals in tree-ring width and wood anatomical traits using increment cores. Winter conditions [...] Read more.
Quercus faginea Lam., a winter-deciduous oak native to the Iberian Peninsula, typically grows under a Mediterranean climate. To identify the main drivers influencing radial wood increment, we analyzed the climatic signals in tree-ring width and wood anatomical traits using increment cores. Winter conditions influenced both latewood width and earlywood vessel size in the first row. Latewood was positively correlated with precipitation and temperature, with the long-term positive effect of winter water supply supported by SPEI. In contrast, vessel size showed negative correlations, also reflecting a long-term negative effect of winter precipitation. Consequently, conditions that enhanced latewood width and overall tree-ring growth appear to be associated with the formation of smaller earlywood vessels. Although ample winter precipitation replenishes soil water reserves and supports prolonged wood formation, it may also induce anaerobic soil conditions that promote root fermentation, depleting carbohydrates needed for cell turgor and expansion, and ultimately regulating earlywood vessel size. This physiological decoupling may help explain the lack of a significant correlation between latewood width and earlywood vessel size, underscoring their independent responses to environmental influences. Our findings highlighted the complex interplay between various climatic conditions affecting Q. faginea, with implications for understanding its adaptive capacity in changing climates. Full article
(This article belongs to the Section Forest Ecophysiology and Biology)
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22 pages, 7156 KiB  
Communication
Water Management, Environmental Challenges, and Rehabilitation Strategies in the Khyargas Lake–Zavkhan River Basin, Western Mongolia: A Case Study of Ereen Lake
by Tseren Ochir Soyol-Erdene, Ganbat Munguntsetseg, Zambuu Burmaa, Ulziibat Bilguun, Shagijav Oyungerel, Soninkhishig Nergui, Nyam-Osor Nandintsetseg, Michael Walther and Ulrich Kamp
Geographies 2025, 5(3), 38; https://doi.org/10.3390/geographies5030038 - 1 Aug 2025
Viewed by 368
Abstract
The depletion of water resources caused by climate change and human activities is a pressing global issue. Lake Ereen is one of the ten natural landmarks of the Gobi-Altai of western Mongolia is included in the list of “important areas for birds” recognized [...] Read more.
The depletion of water resources caused by climate change and human activities is a pressing global issue. Lake Ereen is one of the ten natural landmarks of the Gobi-Altai of western Mongolia is included in the list of “important areas for birds” recognized by the international organization Birdlife. However, the construction of the Taishir Hydroelectric Power Station, aimed at supplying electricity to the western provinces of Mongolia, had a detrimental effect on the flow of the Zavkhan River, resulting in a drying-up and pollution of Lake Ereen, which relies on the river as its water source. This study assesses the pollution levels in Ereen Lake and determines the feasibility of its rehabilitation by redirecting the flow of the Zavkhan River. Field studies included the analysis of water quality, sediment contamination, and the composition of flora. The results show that the concentrations of ammonium, chlorine, fluorine, and sulfate in the lake water exceed the permissible levels set by the Mongolian standard. Analyses of elements from sediments revealed elevated levels of arsenic, chromium, and copper, exceeding international sediment quality guidelines and posing risks to biological organisms. Furthermore, several species of diatoms indicative of polluted water were discovered. Lake Ereen is currently in a eutrophic state and, based on a water quality index (WQI) of 49.4, also in a “polluted” state. Mass balance calculations and box model analysis determined the period of pollutant replacement for two restoration options: drying-up and complete removal of contaminated sediments and plants vs. dilution-flushing without direct interventions in the lake. We recommend the latter being the most efficient, eco-friendly, and cost-effective approach to rehabilitate Lake Ereen. Full article
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13 pages, 1486 KiB  
Article
Evaluation of Miscible Gas Injection Strategies for Enhanced Oil Recovery in High-Salinity Reservoirs
by Mohamed Metwally and Emmanuel Gyimah
Processes 2025, 13(8), 2429; https://doi.org/10.3390/pr13082429 - 31 Jul 2025
Viewed by 229
Abstract
This study presents a comprehensive evaluation of miscible gas injection (MGI) strategies for enhanced oil recovery (EOR) in high-salinity reservoirs, with a focus on the Raleigh Oil Field. Using a calibrated Equation of State (EOS) model in CMG WinProp™, eight gas injection scenarios [...] Read more.
This study presents a comprehensive evaluation of miscible gas injection (MGI) strategies for enhanced oil recovery (EOR) in high-salinity reservoirs, with a focus on the Raleigh Oil Field. Using a calibrated Equation of State (EOS) model in CMG WinProp™, eight gas injection scenarios were simulated to assess phase behavior, miscibility, and swelling factors. The results indicate that carbon dioxide (CO2) and enriched separator gas offer the most technically and economically viable options, with CO2 demonstrating superior swelling performance and lower miscibility pressure requirements. The findings underscore the potential of CO2-EOR as a sustainable and effective recovery method in pressure-depleted, high-salinity environments. Full article
(This article belongs to the Special Issue Recent Developments in Enhanced Oil Recovery (EOR) Processes)
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18 pages, 2207 KiB  
Article
CSF1R-Dependent Microglial Repopulation and Contact-Dependent Inhibition of Proliferation In Vitro
by Rie Nakai, Kuniko Kohyama, Yasumasa Nishito and Hiroshi Sakuma
Brain Sci. 2025, 15(8), 825; https://doi.org/10.3390/brainsci15080825 (registering DOI) - 31 Jul 2025
Viewed by 174
Abstract
Murine microglia exhibit rapid self-renewal upon removal from the postnatal brain. However, the signaling pathways that regulate microglial repopulation remain largely unclear. To address this knowledge gap, we depleted microglia from mixed glial cultures using anti-CD11b magnetic particles and cultured them for 4 [...] Read more.
Murine microglia exhibit rapid self-renewal upon removal from the postnatal brain. However, the signaling pathways that regulate microglial repopulation remain largely unclear. To address this knowledge gap, we depleted microglia from mixed glial cultures using anti-CD11b magnetic particles and cultured them for 4 weeks to monitor their repopulation ability in vitro. Flow cytometry and immunocytochemistry revealed that anti-CD11b bead treatment effectively eliminated >95% of microglia in mixed glial cultures. Following removal, the number of CX3CR1-positive microglia gradually increased; when a specific threshold was reached, repopulation ceased without any discernable rise in cell death. Cell cycle and 5-ethynyl-2′-deoxyuridine incorporation assays suggested the active proliferation of repopulating microglia at d7. Time-lapse imaging demonstrated post-removal division of microglia. Colony-stimulating factor 1 receptor-phosphoinositide 3-kinase-protein kinase B signaling was identified as crucial for microglial repopulation, as pharmacological inhibition or neutralization of the pathway significantly abrogated repopulation. Transwell cocultures revealed that resident microglia competitively inhibited microglial proliferation probably through contact inhibition. This in vitro microglial removal system provides valuable insights into the mechanisms underlying microglial proliferation. Full article
(This article belongs to the Section Neuroglia)
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26 pages, 12136 KiB  
Article
Integrated Analysis of Satellite and Geological Data to Characterize Ground Deformation in the Area of Bologna (Northern Italy) Using a Cluster Analysis-Based Approach
by Alberto Manuel Garcia Navarro, Celine Eid, Vera Rocca, Christoforos Benetatos, Claudio De Luca, Giovanni Onorato and Riccardo Lanari
Remote Sens. 2025, 17(15), 2645; https://doi.org/10.3390/rs17152645 - 30 Jul 2025
Viewed by 260
Abstract
This study investigates ground deformations in the southeastern Po Plain (northern Italy), focusing on the Bologna area—a densely populated region affected by natural and anthropogenic subsidence. Ground deformations in the area result from geological processes (e.g., sediment compaction and tectonic activity) and human [...] Read more.
This study investigates ground deformations in the southeastern Po Plain (northern Italy), focusing on the Bologna area—a densely populated region affected by natural and anthropogenic subsidence. Ground deformations in the area result from geological processes (e.g., sediment compaction and tectonic activity) and human activities (e.g., ground water production and underground gas storage—UGS). We apply a multidisciplinary approach integrating subsurface geology, ground water production, advanced differential interferometry synthetic aperture radar—DInSAR, gas storage data, and land use information to characterize and analyze the spatial and temporal variations in vertical ground deformations. Seasonal and trend decomposition using loess (STL) and cluster analysis techniques are applied to historical DInSAR vertical time series, targeting three representatives areas close to the city of Bologna. The main contribution of the study is the attempt to correlate the lateral extension of ground water bodies with seasonal ground deformations and water production data; the results are validated via knowledge of the geological characteristics of the uppermost part of the Po Plain area. Distinct seasonal patterns are identified and correlated with ground water production withdrawal and UGS operations. The results highlight the influence of superficial aquifer characteristics—particularly the geometry, lateral extent, and hydraulic properties of sedimentary bodies—on the ground movements behavior. This case study outlines an effective multidisciplinary approach for subsidence characterization providing critical insights for risk assessment and mitigation strategies, relevant for the future development of CO2 and hydrogen storage in depleted reservoirs and saline aquifers. Full article
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14 pages, 8505 KiB  
Article
Overexpression of Ent-Kaurene Synthase Genes Enhances Gibberellic Acid Biosynthesis and Improves Salt Tolerance in Anoectochilus roxburghii (Wall.) Lindl.
by Lin Yang, Fuai Sun, Shanyan Zhao, Hangying Zhang, Haoqiang Yu, Juncheng Zhang and Chunyan Yang
Genes 2025, 16(8), 914; https://doi.org/10.3390/genes16080914 - 30 Jul 2025
Viewed by 235
Abstract
Background: Anoectochilus roxburghii (Wall.) Lindl. (A. roxburghii) was widely used in traditional Chinese medicine and also as a health food in China. Gibberellins (GAs) are plant hormones that regulate various aspects of growth and development in A. roxburghii. Ent-kaurene [...] Read more.
Background: Anoectochilus roxburghii (Wall.) Lindl. (A. roxburghii) was widely used in traditional Chinese medicine and also as a health food in China. Gibberellins (GAs) are plant hormones that regulate various aspects of growth and development in A. roxburghii. Ent-kaurene synthase (KS) plays a crucial role in the biosynthesis of GAs in plants. However, there is limited functional analysis of KS in GA biosynthesis and its effect on salt tolerance, especially in A. roxburghii. Methods: The ArKS genes were cloned from A. roxburghii, and its salt tolerance characteristics were verified by prokaryotic expression. Under salt stress, analyze the regulation of KS gene on GA and active ingredient content by qRT-PCR and HPLC-MS/MS, and explore the mechanism of exogenous GAs promoting active ingredient enrichment by regulating the expression level of the KS under salt stress. Results: The ArKS protein was highly homologous to KSs with other plant species; subcellular localization of KS protein was lacking kytic vacuole. The transformants displayed a significant increase in salt tolerance under the stress conditions of 300 mM NaCl. And the expression of ArKS genes and the GAs accumulation was downregulated under the salt stress; among them, the contents of GA3, GA7, GA8, GA24, and GA34 showed a significant decrease. It was further found that there was an increase (1.36 times) in MDA content and a decrease (0.84 times) in relative chlorophyll content under the salt conditions from A. roxburghii. However, the content of active constituents was elevated from A. roxburghii under the NaCl stress, including polysaccharides, total flavonoids, and free amino acids, which increased by 1.14, 1.23, and 1.44 times, respectively. Interestingly, the ArKS gene expression and the chlorophyll content was increased, MDA content showed a decrease from 2.02 μmoL·g−1 to 1.74 μmoL·g−1 after exogenous addition of GAs, and the elevation of active constituents of polysaccharides, total flavonoids, and free amino acids were increased by 1.02, 1.09, and 1.05 times, implying that GAs depletion mitigated the damage caused by adversity to A. roxburghii. Conclusions: The ArKS gene cloned from A. roxburghii improved the salt tolerance of plants under salt stress by regulating GA content. Also, GAs not only alleviate salt tolerance but also play a key role in the synthesis of active components in A. roxburghii. The functions of KS genes and GAs were identified to provide ideas for improving the salt tolerance and quality of ingredients in artificial cultivation from A. roxburghii. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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22 pages, 2357 KiB  
Article
Targeting GLP-1 Signaling Ameliorates Cystogenesis in a Zebrafish Model of Nephronophthisis
by Priska Eckert, Maike Nöller, Merle Müller, Rebecca Haas, Johannes Ruf, Henriette Franz, Katharina Moos, Jia-ao Yu, Dongfang Zhao, Wanqiu Xie, Melanie Boerries, Gerd Walz and Toma A. Yakulov
Int. J. Mol. Sci. 2025, 26(15), 7366; https://doi.org/10.3390/ijms26157366 - 30 Jul 2025
Viewed by 159
Abstract
Nephronophthisis (NPH) is the leading genetic cause of end-stage renal disease in children and young adults, but no effective disease-modifying therapies are currently available. Here, we identify glucagon-like peptide-1 (GLP-1) signaling as a novel therapeutic target for NPH through a systematic drug repurposing [...] Read more.
Nephronophthisis (NPH) is the leading genetic cause of end-stage renal disease in children and young adults, but no effective disease-modifying therapies are currently available. Here, we identify glucagon-like peptide-1 (GLP-1) signaling as a novel therapeutic target for NPH through a systematic drug repurposing screen in zebrafish. By simultaneously depleting nphp1 and nphp4, we developed a robust zebrafish model that reproduces key features of human NPH, including glomerular cyst formation. Our screen revealed that dipeptidyl peptidase-4 (DPP4) inhibitors (Omarigliptin and Linagliptin) and GLP-1 receptor agonists (Semaglutide) significantly reduce cystogenesis in a dose-dependent manner. Genetic analysis demonstrated that GLP-1 receptor signaling is important for maintaining pronephros integrity, with gcgra and gcgrb (GLP-1 receptor genes) playing a particularly important role. Transcriptomic profiling identified adenosine receptor A2ab (adora2ab) as a key downstream effector of GLP-1 signaling, which regulates ciliary morphology and prevents cyst formation. Notably, nphp1/nphp4 double mutant zebrafish exhibited the upregulation of gcgra as a compensatory mechanism, which might explain their resistance to cystogenesis. This compensation was disrupted by the targeted depletion of GLP-1 receptors or the inhibition of adenylate cyclase, resulting in enhanced cyst formation, specifically in the mutant background. Our findings establish a signaling cascade from GLP-1 receptors to adora2ab in terms of regulating ciliary organization and preventing cystogenesis, offering new therapeutic opportunities for NPH through the repurposing of FDA-approved medications with established safety profiles. Full article
(This article belongs to the Special Issue Zebrafish as a Model in Human Disease: 3rd Edition)
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23 pages, 1084 KiB  
Review
Unraveling the Translational Relevance of β-Hydroxybutyrate as an Intermediate Metabolite and Signaling Molecule
by Dwifrista Vani Pali, Sujin Kim, Keren Esther Kristina Mantik, Ju-Bi Lee, Chan-Young So, Sohee Moon, Dong-Ho Park, Hyo-Bum Kwak and Ju-Hee Kang
Int. J. Mol. Sci. 2025, 26(15), 7362; https://doi.org/10.3390/ijms26157362 - 30 Jul 2025
Viewed by 406
Abstract
β-hydroxybutyrate (BHB) is the most abundant ketone body produced during ketosis, a process initiated by glucose depletion and the β-oxidation of fatty acids in hepatocytes. Traditionally recognized as an alternative energy substrate during fasting, caloric restriction, and starvation, BHB has gained attention for [...] Read more.
β-hydroxybutyrate (BHB) is the most abundant ketone body produced during ketosis, a process initiated by glucose depletion and the β-oxidation of fatty acids in hepatocytes. Traditionally recognized as an alternative energy substrate during fasting, caloric restriction, and starvation, BHB has gained attention for its diverse signaling roles in various physiological processes. This review explores the emerging therapeutic potential of BHB in the context of sarcopenia, metabolic disorders, and neurodegenerative diseases. BHB influences gene expression, lipid metabolism, and inflammation through its inhibition of Class I Histone deacetylases (HDACs) and activation of G-protein-coupled receptors (GPCRs), specifically HCAR2 and FFAR3. These actions lead to enhanced mitochondrial function, reduced oxidative stress, and regulation of inflammatory pathways, with implication for muscle maintenance, neuroprotection, and metabolic regulation. Moreover, BHB’s ability to modulate adipose tissue lipolysis and immune responses highlight its broader potential in managing chronic metabolic conditions and aging. While these findings show BHB as a promising therapeutic agent, further research is required to determine optimal dosing strategies, long-term effects, and its translational potential in clinical settings. Understanding BHB’s mechanisms will facilitate its development as a novel therapeutic strategy for multiple organ systems affected by aging and disease. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies in Skeletal Muscle Diseases)
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19 pages, 1297 KiB  
Article
The Genghis Khan Effect
by Sergio Da Silva, Raul Matsushita and Sergio Bonini
Humans 2025, 5(3), 19; https://doi.org/10.3390/humans5030019 - 30 Jul 2025
Viewed by 228
Abstract
This study examines the impact of reproductive inequality on the long-term survival of Homo sapiens by comparing two reproductive models: the Pareto (power-law) distribution of unequal reproduction and the Gaussian (normal) distribution of equal reproduction. We conducted simulations to explore how genetic diversity, [...] Read more.
This study examines the impact of reproductive inequality on the long-term survival of Homo sapiens by comparing two reproductive models: the Pareto (power-law) distribution of unequal reproduction and the Gaussian (normal) distribution of equal reproduction. We conducted simulations to explore how genetic diversity, measured by heterozygosity, evolves over time. The results predict population crashes due to genetic bottlenecks under both models, but with large differences in timing. We refer to Pareto reproductive inequality as the Genghis Khan effect. This effect accelerates the loss of genetic diversity, increasing the species’ vulnerability to environmental stressors, resource depletion, and genetic drift, and thereby raising the risk of an earlier population collapse. Our findings showcase the importance of reproductive balance for the prolonged presence of Homo sapiens on this planet. Full article
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59 pages, 3467 KiB  
Review
Are Hippocampal Hypoperfusion and ATP Depletion Prime Movers in the Genesis of Alzheimer’s Disease? A Review of Recent Pertinent Observations from Molecular Biology
by Valerie Walker
Int. J. Mol. Sci. 2025, 26(15), 7328; https://doi.org/10.3390/ijms26157328 - 29 Jul 2025
Viewed by 259
Abstract
Alzheimer’s dementia (AD) is a disease of the ageing brain. It begins in the hippocampal region with the epicentre in the entorhinal cortex, then gradually extends into adjacent brain areas involved in memory and cognition. The events which initiate the damage are unknown [...] Read more.
Alzheimer’s dementia (AD) is a disease of the ageing brain. It begins in the hippocampal region with the epicentre in the entorhinal cortex, then gradually extends into adjacent brain areas involved in memory and cognition. The events which initiate the damage are unknown and under intense investigation. Localization to the hippocampus can now be explained by anatomical features of the blood vessels supplying this region. Blood supply and hence oxygen delivery to the area are jeopardized by poor flow through narrowed arteries. In genomic and metabolomic studies, the respiratory chain and mitochondrial pathways which generate ATP were leading pathways associated with AD. This review explores the notion that ATP depletion resulting from hippocampal hypoperfusion has a prime role in initiating damage. Sections cover sensing of ATP depletion and protective responses, vulnerable processes with very heavy ATP consumption (the malate shuttle, the glutamate/glutamine/GABA (γ-aminobutyric acid) cycle, and axonal transport), phospholipid disturbances and peroxidation by reactive oxygen species, hippocampal perfusion and the effects of hypertension, chronic hypoxia, and arterial vasospasm, and an overview of recent relevant genomic studies. The findings demonstrate strong scientific arguments for the proposal with increasing supportive evidence. These lines of enquiry should be pursued. Full article
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38 pages, 6652 KiB  
Review
Remote Sensing Perspective on Monitoring and Predicting Underground Energy Sources Storage Environmental Impacts: Literature Review
by Aleksandra Kaczmarek and Jan Blachowski
Remote Sens. 2025, 17(15), 2628; https://doi.org/10.3390/rs17152628 - 29 Jul 2025
Viewed by 302
Abstract
Geological storage is an integral element of the green energy transition. Geological formations, such as aquifers, depleted reservoirs, and hard rock caverns, are used mainly for the storage of hydrocarbons, carbon dioxide and increasingly hydrogen. However, potential adverse effects such as ground movements, [...] Read more.
Geological storage is an integral element of the green energy transition. Geological formations, such as aquifers, depleted reservoirs, and hard rock caverns, are used mainly for the storage of hydrocarbons, carbon dioxide and increasingly hydrogen. However, potential adverse effects such as ground movements, leakage, seismic activity, and environmental pollution are observed. Existing research focuses on monitoring subsurface elements of the storage, while on the surface it is limited to ground movement observations. The review was carried out based on 191 research contributions related to geological storage. It emphasizes the importance of monitoring underground gas storage (UGS) sites and their surroundings to ensure sustainable and safe operation. It details surface monitoring methods, distinguishing geodetic surveys and remote sensing techniques. Remote sensing, including active methods such as InSAR and LiDAR, and passive methods of multispectral and hyperspectral imaging, provide valuable spatiotemporal information on UGS sites on a large scale. The review covers modelling and prediction methods used to analyze the environmental impacts of UGS, with data-driven models employing geostatistical tools and machine learning algorithms. The limited number of contributions treating geological storage sites holistically opens perspectives for the development of complex approaches capable of monitoring and modelling its environmental impacts. Full article
(This article belongs to the Special Issue Advancements in Environmental Remote Sensing and GIS)
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