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Search Results (41,047)

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16 pages, 3635 KiB  
Article
Itchy E3 Ubiquitin Ligase-Mediated Ubiquitination of Ferritin Light Chain Contributes to Endothelial Ferroptosis in Atherosclerosis
by Yi Zeng, Shuai Fu, Yuwei Xia, Guoliang Meng and Xiaole Xu
Int. J. Mol. Sci. 2024, 25(24), 13524; https://doi.org/10.3390/ijms252413524 - 17 Dec 2024
Abstract
This research seeks to investigate the function and fundamental mechanisms of Itchy E3 ubiquitin ligase (ITCH), a HECT (homologous to E6AP carboxyl terminus)-type E3 ubiquitin ligase, in endothelial ferroptosis, particularly in the context of atherosclerosis, which has been underexplored. The levels of ITCH [...] Read more.
This research seeks to investigate the function and fundamental mechanisms of Itchy E3 ubiquitin ligase (ITCH), a HECT (homologous to E6AP carboxyl terminus)-type E3 ubiquitin ligase, in endothelial ferroptosis, particularly in the context of atherosclerosis, which has been underexplored. The levels of ITCH protein in the aortas of mice with atherosclerosis were analyzed. Constructs for ITCH RNA interference were generated and introduced into human aortic endothelial cells (HAECs). The findings indicated that ITCH protein expression was elevated in atherosclerotic mice and HAECs exposed to oxidized low-density lipoprotein (ox-LDL). ITCH downregulation significantly mitigated ox-LDL-induced endothelial injury and dysfunction. Reducing ITCH expression inhibited ox-LDL-induced endothelial ferroptosis. This study also revealed that ITCH mediates ox-LDL-induced ubiquitin-dependent degradation of ferritin light chain (FTL) in HAECs. The protective impact of ITCH knockdown against ox-LDL-induced ferroptosis and endothelial injury was reversed by FTL siRNA. Additionally, in vivo experiments showed that inhibiting ITCH reduced atherosclerosis progression and reversed ferroptosis in the aorta, with an associated increase in FTL protein expression in the aortas of mice. This study demonstrates that ITCH interacts with and regulates the stability of the FTL protein via the ubiquitin–proteasome system, contributing to ox-LDL-induced ferroptosis and endothelial cell dysfunction. Targeting components of the ITCH-FTL pathway holds potential as a therapeutic strategy against atherosclerosis. Full article
(This article belongs to the Section Biochemistry)
14 pages, 2139 KiB  
Article
Effects of Straw at Different Fermentation Phases on Soil Nutrient Availability and Microbial Activity
by Tian Chen, Yuxia Mei, Xinwei Liu, Zhuqing Zhao and Yunxiang Liang
Agronomy 2024, 14(12), 3005; https://doi.org/10.3390/agronomy14123005 - 17 Dec 2024
Abstract
Returning corn straw to the field is beneficial for improving soil fertility, but the fermentation phase significantly affects the dissolved organic carbon (DOC) content. However, there is limited research on the effects of straw at different fermentation phases on soil microorganisms and soil [...] Read more.
Returning corn straw to the field is beneficial for improving soil fertility, but the fermentation phase significantly affects the dissolved organic carbon (DOC) content. However, there is limited research on the effects of straw at different fermentation phases on soil microorganisms and soil nutrients. This study examined the effects of high-temperature fermentation phase straw (HF) and completely fermentation phase straw (CF) on soil nutrient activation and microorganism activity through pot experiments. The pot experiment results indicated a significant increase in soil DOC content following the application of corn straw, among which the high-temperature fermentation phase straw treatment (THF) exhibited the highest DOC content, which was 14% higher than the completely fermentation phase straw treatment (TCF). THF also significantly increased soil alkaline hydrolyzed nitrogen and available phosphorus content as well as urease and phosphatase, and promoted the uptake of nitrogen and phosphorus from soil by Brassica chinensis. THF significantly enhanced bacterial diversity and reduced the presence of pathogenic fungi. Compared to the TCF, the relative proportion of Fusarium under the THF decreased by 32.24%, effectively mitigating the impact of pathogenic fungi. THF also increased soil DOC content, enriched beneficial microbial community structure, increased soil enzyme activity, activated soil nutrients, thereby promoting the uptake of nitrogen and phosphorus by crops. Taken together, the results reveal that the application of high-temperature fermentation phase straw is conducive to soil fertilization and crop growth. Full article
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Figure 1

Figure 1
<p>Temporal changes of composting temperature (<b>a</b>), DOC content (<b>b</b>), and TOC content (<b>c</b>) during the corn straw compost. DOC, dissolved organic carbon; TOC, total organic carbon.</p>
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<p>Plant biomass of <span class="html-italic">B. chinensis</span> under different treatments. Note: T<sub>CK</sub>, control with no straw; T<sub>UF</sub>, treatment with unfermented straw; T<sub>HF</sub>, treatment with high-temperature fermentation phase straw; T<sub>CF</sub>, treatment with completely fermentation phase straw. Different lowercase letters above the bars indicate statistically significant differences (<span class="html-italic">p</span> &lt; 0.05) according to Tukey’s HSD test.</p>
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<p>Soil alkali-hydrolyzed nitrogen (AN) (<b>a</b>), urease (<b>b</b>), available phosphorus (AP) (<b>c</b>), phosphatase (<b>d</b>), AK (available potassium) (<b>e</b>), TOC (<b>f</b>) and DOC (<b>g</b>) under different treatments. Note: T<sub>CK</sub>, control with no straw; T<sub>UF</sub>, treatment with unfermented straw; T<sub>HF</sub>, treament with high-temperature fermentation phase straw; T<sub>CF</sub>, treatment with completely fermentation phase straw. Different lowercase letters above the bars indicate statistically significant differences (<span class="html-italic">p</span> &lt; 0.05) according to Tukey’s HSD test.</p>
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<p>Effects of different treatments on the growth of <span class="html-italic">Bacillus subtilis</span>. Note: T<sub>CK</sub>, control with no straw; T<sub>UF</sub>, treatment with unfermented straw; T<sub>HF</sub>, treament with high-temperature fermentation phase straw; T<sub>CF</sub>, treatment with completely fermentation phase straw. Different lowercase letters above the bars indicate statistically significant differences (<span class="html-italic">p</span> &lt; 0.05) according to Tukey’s HSD test.</p>
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<p>Changes in soil bacterial (<b>a</b>) and fungal (<b>b</b>) α-diversity in soil under different treatments represented by Chao1 and Shannon indices. Non-metric multidimensional scaling (NMDS) of bacterial (<b>c</b>) and fungal (<b>d</b>) community composition of soil samples. Note: T<sub>CK</sub>, control with no straw; T<sub>UF</sub>, treatment with unfermented straw; T<sub>HF</sub>, treament with high-temperature fermentation phase straw; T<sub>CF</sub>, treatment with completely fermentation phase straw.</p>
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<p>Soil bacterial (<b>A</b>) and fungal (<b>B</b>) composition at genus level under 4 different straw treatments. Note: T<sub>CK</sub>, control with no straw; T<sub>UF</sub>, treatment with unfermented straw; T<sub>HF</sub>, treament with high-temperature fermentation phase straw; T<sub>CF</sub>, treatment with completely fermentation phase straw.</p>
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<p>(<b>a</b>–<b>d</b>) Relative proportion of 4 different bacterial genera under different treatments. (<b>e</b>–<b>h</b>) Relative proportion of 4 different fungal genera under different treatments. Note: T<sub>CK</sub>, control with no straw; T<sub>UF</sub>, treatment with unfermented straw; T<sub>HF</sub>, treament with high-temperature fermentation phase straw; T<sub>CF</sub>, treatment with completely fermentation phase straw. Different lowercase letters above the bars indicate statistically significant differences (<span class="html-italic">p</span> &lt; 0.05) according to Tukey’s HSD test.</p>
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<p>Redundancy analysis (RDA) of soil physicochemical properties with the soil bacterial (<b>a</b>) and fungal (<b>b</b>) proportion under different straw treatments. Note: T<sub>CK</sub>, control with no straw; T<sub>UF</sub>, treatment with unfermented straw; T<sub>HF</sub>, treament with high-temperature fermentation phase straw; T<sub>CF</sub>, treatment with completely fermentation phase straw. The length of arrows presents the magnitude of correlation between environmental factors and bacterial community structure. The direction of arrows presents the variation tendency of environmental factors.</p>
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29 pages, 30490 KiB  
Article
Ecosystem Services Trade-Offs in the Chaohu Lake Basin Based on Land-Use Scenario Simulations
by Aibo Jin, Gachen Zhang, Ping Ma and Xiangrong Wang
Land 2024, 13(12), 2210; https://doi.org/10.3390/land13122210 - 17 Dec 2024
Abstract
Amid global environmental degradation, understanding the spatiotemporal dynamics and trade-offs of ecosystem services (ESs) under varying land-use scenarios is critical for advancing the sustainable development of social–ecological systems. This study analyzed the Chaohu Lake Basin (CLB), focusing on four scenarios: natural development (ND), [...] Read more.
Amid global environmental degradation, understanding the spatiotemporal dynamics and trade-offs of ecosystem services (ESs) under varying land-use scenarios is critical for advancing the sustainable development of social–ecological systems. This study analyzed the Chaohu Lake Basin (CLB), focusing on four scenarios: natural development (ND), economic priority (ED), ecological protection (EP), and sustainable development (SD). Using the PLUS model and multi-objective genetic algorithm (MOGA), land-use changes for 2030 were simulated, and their effects on ESs were assessed quantitatively and qualitatively. The ND scenario led to significant declines in cropland (3.73%) and forest areas (0.18%), primarily due to construction land expansion. The EP scenario curbed construction land growth, promoted ecosystem recovery, and slightly increased cropland by 0.05%. The SD scenario achieved a balance between ecological and economic goals, maintaining relative stability in ES provision. Between 2010 and 2020, construction land expansion, mainly concentrated in central Hefei City, led to a marked decline in habitat quality (HQ) and landscape aesthetics (LA), whereas water yield (WY) and soil retention (SR) improved. K-means clustering analysis identified seven ecosystem service bundles (ESBs), revealing significant spatial heterogeneity. Bundles 4 through 7, concentrated in mountainous and water regions, offered high biodiversity maintenance and ecological regulation. In contrast, critical ES areas in the ND and ED scenarios faced significant encroachment, resulting in diminished ecological functions. The SD scenario effectively mitigated these impacts, maintaining stable ES provision and ESB distribution. This study highlights the profound effects of different land-use scenarios on ESs, offering insights into sustainable planning and ecological restoration strategies in the CLB and comparable regions. Full article
27 pages, 3554 KiB  
Article
Optimization of Active Distribution Network Operation with SOP Considering Reverse Power Flow
by Zhanhui Ma and Fang Cao
Appl. Sci. 2024, 14(24), 11797; https://doi.org/10.3390/app142411797 - 17 Dec 2024
Abstract
As the penetration of distributed renewable energy increases, the phenomenon of bidirectional power flow in distribution networks becomes increasingly severe. Traditional regulation devices like OLTC (on-load tap changer) and CB (capacitor bank) cannot effectively mitigate reverse power flow in distribution networks due to [...] Read more.
As the penetration of distributed renewable energy increases, the phenomenon of bidirectional power flow in distribution networks becomes increasingly severe. Traditional regulation devices like OLTC (on-load tap changer) and CB (capacitor bank) cannot effectively mitigate reverse power flow in distribution networks due to their limitations. The transmission capacity of the distribution network under reverse power flow is approximately 50% of the rated capacity of the OLTC, leading to issues such as voltage limit violations and high wind and solar curtailment rates. This paper proposes a method for calculating the reverse power flow delivery capacity of distribution networks, quantitatively describing the distribution network’s delivery limits for reverse power flow. Based on this, a joint optimization model for multiple distribution networks with an SOP is established. The SOP is utilized to share reverse power flow delivery capacity among multiple distribution networks, enhancing operational economy and increasing the accommodation of the DG. Finally, the method’s effectiveness and correctness are verified in the IEEE 33-node system. The results validate that while joint operation does not enhance the reverse flow transmission capacity of a single distribution network, it can, through the shared reverse flow transmission capacity approach, elevate the reverse flow transmission capacity to approximately 70% during the majority of time periods. Full article
(This article belongs to the Special Issue New Insights into Power Systems)
26 pages, 1384 KiB  
Article
A Moderate Intake of Beer Improves Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in a High-Fat Diet (HFD)-Induced Mouse Model
by Andrea Vornoli, Aymen Souid, Barbara Lazzari, Federica Turri, Flavia Pizzi, Emilia Bramanti, Beatrice Campanella, Cheherazade Trouki, Andrea Raffaelli, Marta Wójcik, Clara Maria Della Croce, Lucia Giorgetti, Vincenzo Longo, Emanuele Capra and Luisa Pozzo
Molecules 2024, 29(24), 5954; https://doi.org/10.3390/molecules29245954 - 17 Dec 2024
Abstract
Beer and its components show potential for reducing hepatic steatosis in rodent models through multiple mechanisms. This study aimed to evaluate beer’s anti-steatotic effects in a high-fat diet (HFD)-induced mouse model of Metabolic dysfunction-Associated Liver Disease (MASLD) and to explore the underlying mechanisms. [...] Read more.
Beer and its components show potential for reducing hepatic steatosis in rodent models through multiple mechanisms. This study aimed to evaluate beer’s anti-steatotic effects in a high-fat diet (HFD)-induced mouse model of Metabolic dysfunction-Associated Liver Disease (MASLD) and to explore the underlying mechanisms. In the HFD group, steatosis was confirmed by altered blood parameters, weight gain, elevated liver lipid content, and histological changes. These markers were normalized in the HFD+beer group, reaching levels similar to the control (CTR) group. Protein carbonylation and lipid peroxidation levels were consistent across all groups, suggesting that the model represents an early stage of MASLD without oxidative stress. Transcriptomic and CpG methylation analyses revealed clear distinctions between the CTR and HFD groups. RNA sequencing identified 162 differentially expressed genes (DEGs) between the CTR and HFD groups, primarily related to inflammation and lipid regulation. Beer consumption modified the health of the HFD mice, affecting inflammation but not lipid homeostasis (CTR vs. HFD+beer, DEGs = 43). The CpG methylation analysis indicated that beer lowered methylation, impacting genes linked to lipid accumulation and inflammation. A cecal metabolite analysis suggested that beer improved short-chain fatty acid metabolism (SCFA). In summary, a moderate beer intake may mitigate MASLD by modulating lipid metabolism and SCFA pathways, likely through polyphenol activity. Full article
(This article belongs to the Special Issue Advances in Natural Products and Their Biological Activities)
26 pages, 4638 KiB  
Systematic Review
Heat Stress Prevention in Construction: A Systematic Review and Meta-Analysis of Risk Factors and Control Strategies
by Mehdi Torbat Esfahani, Ibukun Awolusi and Yilmaz Hatipkarasulu
Int. J. Environ. Res. Public Health 2024, 21(12), 1681; https://doi.org/10.3390/ijerph21121681 - 17 Dec 2024
Abstract
In hot and humid work environments, construction workers can experience heat stress and heat-related illnesses (HRIs). While several studies have investigated engineering and administrative control methods to prevent certain heat stress risk factors, a comprehensive understanding of all existing risk factors and their [...] Read more.
In hot and humid work environments, construction workers can experience heat stress and heat-related illnesses (HRIs). While several studies have investigated engineering and administrative control methods to prevent certain heat stress risk factors, a comprehensive understanding of all existing risk factors and their corresponding control strategies is still lacking. It is crucial to identify gaps in current control strategies and develop a safety management framework for effective heat stress control by implementing existing measures. In addition, the effectiveness of the most common control strategies must be rigorously evaluated to ensure their efficacy and to guide future research aimed at enhancing these strategies or developing more effective ones. This study employed a mixed literature review methodology to address this knowledge gap. A structured literature review investigated and synthesized heat stress risk factors and control methods to find the gaps in control options to address underestimated risk factors. Furthermore, a comprehensive systematic literature review, including trend analysis, scientometric analysis, and meta-analysis, determined research foci and evaluated the effectiveness of the heat stress control methods. The scientometric analysis identified 11 clusters, encompassing key research themes such as environmental risk factors (e.g., high-temperature environments, climate change), administrative controls (e.g., work–rest schedules, climate change risk assessment), and personal interventions (e.g., cooling vests and sleep-related strategies). These findings highlight that the most commonly studied control methods are cooling vests, work–rest schedules, and cooling interventions. According to these results and the availability of quantitative results, the meta-analysis evaluated nine datasets of reductions in core body temperature by using types of cooling vests and anti-heat-stress uniforms and established the significant effectiveness of this control strategy in mitigating heat stress with a medium effect size. Moreover, five potential research studies have been identified to address gaps in control strategies for certain underestimated risk factors, including leveraging sensor technologies, conducting control training, dynamic work–rest schedules, using cutting-edge PPE, and governmental initiatives. Insights gained from this study enhance decision making for resource allocation, selection of control options, and intervention prioritization within a heat-stress-control framework based on the safety management system. The findings also highlight the effectiveness of cooling vests and areas that need to be developed, and evaluate potential heat-stress-control methods in construction. Full article
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Figure 1
<p>Research process and steps.</p>
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<p>Searching procedures.</p>
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<p>Results of publication trend analysis: (<b>a</b>) number of publications per year; (<b>b</b>) publications by country; (<b>c</b>) number of publications per journal.</p>
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<p>Clusters with indexing terms.</p>
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<p>Heat stress risk factors.</p>
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<p>Heat stress control methods.</p>
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<p>Integrated framework of heat stress control strategies within the safety management system.</p>
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<p>Forest plot of meta-analysis results [<a href="#B15-ijerph-21-01681" class="html-bibr">15</a>,<a href="#B16-ijerph-21-01681" class="html-bibr">16</a>,<a href="#B17-ijerph-21-01681" class="html-bibr">17</a>,<a href="#B71-ijerph-21-01681" class="html-bibr">71</a>,<a href="#B73-ijerph-21-01681" class="html-bibr">73</a>,<a href="#B82-ijerph-21-01681" class="html-bibr">82</a>,<a href="#B85-ijerph-21-01681" class="html-bibr">85</a>,<a href="#B86-ijerph-21-01681" class="html-bibr">86</a>,<a href="#B87-ijerph-21-01681" class="html-bibr">87</a>].</p>
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24 pages, 1421 KiB  
Review
From Vineyard to Value: A Circular Economy Approach to Viticulture Waste
by Mariagrazia Provenzano, Francesco Pacchera, Cecilia Silvestri and Alessandro Ruggieri
Resources 2024, 13(12), 172; https://doi.org/10.3390/resources13120172 - 17 Dec 2024
Abstract
Due to its significant environmental impact, the wine industry is one of the most analyzed agri-food sectors in terms of sustainability. These include waste emission, intensive land use, and high transport-related carbon footprint. The circular economy represents an opportunity to mitigate these impacts [...] Read more.
Due to its significant environmental impact, the wine industry is one of the most analyzed agri-food sectors in terms of sustainability. These include waste emission, intensive land use, and high transport-related carbon footprint. The circular economy represents an opportunity to mitigate these impacts by promoting the valorization of wine waste. Through a systematic literature review, this research provides an overview of studies from 2018 to 2024 that deal with the transformation of wine waste, in particular vinification residues, into resources. The research covers the commodity sectors in which wine waste is reused, such as Food, Agriculture, and Energy. The analysis of the sample reveals that the countries in which the issue of valorization of wine waste is most studied are Italy, Spain, and Portugal. The study encourages a better integration of waste in the wine sector into business practices by assessing the environmental and economic impact. From a management point of view, the aim is to inform companies about effective waste management practices in order to promote the development of a more sustainable wine industry. Future research will focus on evaluating the effectiveness of these valorization pathways, also through case studies of good practice in implementing a circular business model. Full article
20 pages, 8527 KiB  
Article
Butyrolactone-I from Marine Fungal Metabolites Mitigates Heat-Stress-Induced Apoptosis in IPEC-J2 Cells and Mice Through the ROS/PERK/CHOP Signaling Pathway
by Xueting Niu, Shengwei Chen, Xinchen Wang, Jiaying Wen, Xiaoxi Liu, Yanhong Yong, Zhichao Yu, Xingbing Ma, A. M. Abd El-Aty and Xianghong Ju
Mar. Drugs 2024, 22(12), 564; https://doi.org/10.3390/md22120564 - 17 Dec 2024
Abstract
Heat stress poses a significant challenge to animal husbandry, contributing to oxidative stress, intestinal mucosal injury, and apoptosis, which severely impact animal health, growth, and production efficiency. The development of safe, sustainable, and naturally derived solutions to mitigate these effects is critical for [...] Read more.
Heat stress poses a significant challenge to animal husbandry, contributing to oxidative stress, intestinal mucosal injury, and apoptosis, which severely impact animal health, growth, and production efficiency. The development of safe, sustainable, and naturally derived solutions to mitigate these effects is critical for advancing sustainable agricultural practices. Butyrolactone-I (BTL-I), a bioactive compound derived from deep-sea fungi (Aspergillus), shows promise as a functional feed additive to combat heat stress in animals. This study explored the protective effects of BTL-I against heat-stress-induced oxidative stress and apoptosis in IPEC-J2 cells and mice. Our findings demonstrated that BTL-I effectively inhibited the heat-stress-induced upregulation of HSP70 and HSP90, alleviating intestinal heat stress. Both in vitro and in vivo experiments revealed that heat stress increased intestinal cell apoptosis, with a significant upregulation of Bax/Bcl-2 expression, while BTL-I pretreatment significantly reduced apoptosis-related protein levels, showcasing its protective effects. Furthermore, BTL-I suppressed oxidative stress markers (ROS and MDA) while enhancing antioxidant activity (SOD levels). BTL-I also reduced the expression of p-PERK, p-eIF2α, ATF4, and CHOP, mitigating oxidative and endoplasmic reticulum stress in intestinal cells. In conclusion, BTL-I demonstrates the potential to improve animal resilience to heat stress, supporting sustainable livestock production systems. Its application as a natural, eco-friendly feed additive will contribute to the development of sustainable agricultural practices. Full article
(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)
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Graphical abstract

Graphical abstract
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<p>Effect of BTL-I on the expression of related factors in heat-shocked IPEC-J2 cells. IPEC-J2 cells were treated with different concentrations of BTL-I (10, 20, or 50 μM) for 24 h and then coincubated with the heat shock (HS) group in a 5% CO<sub>2</sub> incubator at 42 °C for 1.5 h. Cell viability was determined via a CCK8 assay. (<b>A</b>) Effects of BTL-I on the viability of IPEC-J2 cells; (<b>B</b>) effects of heat shock treatment on the viability of IPEC-J2 cells; (<b>C</b>) effects of BTL-I and heat shock cotreatment on IPEC-J2 cells; and (<b>D</b>–<b>F</b>) the expression levels of the heat shock proteins HSP70 and HSP90 were detected via Western blotting. The results are expressed as the means ± SEMs. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 compared with the control group; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 compared with the HS group.</p>
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<p>Effects of BTL-I on IPEC-J2 cell apoptosis after heat shock. (<b>A</b>) Flow cytometry analysis of the cell apoptosis rate; (<b>B</b>,<b>C</b>) qPCR analysis of <span class="html-italic">Bax</span> and <span class="html-italic">Bcl-2</span>; (<b>D</b>,<b>E</b>) Western blotting analysis of Bax and Bcl-2; and (<b>F</b>,<b>G</b>) IF analysis of Bax and Bcl-2; the red fluorescence represents Bcl-2 and Bax protein expression, and the blue fluorescence corresponds to the cell nuclei; the results are expressed as the means ± SEMs. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 compared with the control group; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 compared with the HS group.</p>
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<p>Effect of BTL-I on the ROS/PERK/CHOP signaling pathway in IPEC-J2 cells subjected to heat shock. (<b>A</b>–<b>C</b>) ELISA analysis of the levels of the oxidative markers ROS, MDA, and SOD; (<b>D</b>,<b>E</b>) qPCR analysis of the levels of the PERK/CHOP signaling pathway markers <span class="html-italic">ATF4</span> and <span class="html-italic">CHOP</span>; (<b>F</b>–<b>J</b>) Western blotting analysis of the levels of the PERK/CHOP signaling pathway markers p-PERK, PERK, p-eIF2α, eIF2α, ATF4, and CHOP; and (<b>K</b>) IF analysis of the levels of the PERK/CHOP signaling pathway marker ATF4. The results are expressed as the means ± SEMs. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 compared with the control group; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 compared with the HS group.</p>
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<p>Effects of ROS scavengers on the PERK/CHOP signaling pathway and apoptosis in heat-shocked IPEC-J2 cells. IPEC-J2 cells were treated with BTL-I (50 μM) or NAC (1 mM) for 24 h or 3 h, respectively, and then placed together with the heat shock (HS) group in a cell incubator at 42 °C and 5% CO<sub>2</sub> for 1.5 h. (<b>A</b>) ELISA analysis of the oxidative marker ROS. (<b>B</b>–<b>G</b>) Western blot analysis of the expression of the PERK/CHOP signaling pathway markers p-PERK, PERK, p-eIF2α, eIF2α, ATF4, and CHOP. (<b>H</b>–<b>L</b>) Western blot analysis of the expression of the apoptosis markers Bax/Bcl-2 and procaspase 3. The results are expressed as the means ± SEMs. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 compared with the control group; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 compared with the HS group.</p>
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<p>Effect of ROS scavengers on apoptosis in heat-shocked IPEC-J2 cells. (<b>A</b>,<b>B</b>) IF analysis of the apoptosis markers Bax and Bcl-2.</p>
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<p>Effect of an ER stress inhibitor on the apoptosis of heat-shocked IPEC-J2 cells. IPEC-J2 cells were treated with BTL-I (50 μM) or 4-PBA (1 mM) for 24 h or 3 h, respectively, and then placed together with the heat shock (HS) group in a cell incubator at 42 °C and 5% CO<sub>2</sub> for 1.5 h. (<b>A</b>–<b>F</b>) Western blot analysis of the expression of the PERK/CHOP signaling pathway markers p-PERK, PERK, p-eIF2α, eIF2α, ATF4, and CHOP. (<b>G</b>–<b>K</b>) Western blot analysis of the expression of the apoptosis markers Bax/Bcl-2 and procaspase 3. The results are expressed as the means ± SEMs. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 compared with the control group; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 compared with the HS group.</p>
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<p>Effect of an endoplasmic reticulum inhibitor on the apoptosis of heat-shocked IPEC-J2 cells. (<b>A</b>,<b>B</b>) IF analysis of the apoptosis markers Bax and Bcl-2.</p>
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<p>Protective effect of BTL-I on heat-stressed mice. The normal control group (CON) was exposed to 24 ± 1 °C and treated with PBS (0.2 mL), the heat stress group (HS) was subjected to 40 ± 1 °C for 4 h per day, the HS group had a low oral BTL-I concentration (1 mg/kg) (LOW), and the HS group had a high oral BTL-I concentration (5 mg/kg) (HIGH). Clinical changes were recorded, and colon tissues were collected. (<b>A</b>–<b>D</b>) qPCR and Western blotting analysis of the effects of BTL-I on HSP70 and HSP90 proteins; (<b>E</b>) water intake of the mice during the test; (<b>F</b>) body weight changes in the mice during the test; (<b>G</b>) body temperature changes; and (<b>H</b>,<b>I</b>) colon length of the mice during the test; the results are expressed as the means ± SEMs. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 compared with the control group; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 compared with the HS group.</p>
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<p>Effects of BTL-I on apoptosis in heat-stressed mice. (<b>A</b>) The effects of BTL-I on the expression of the apoptotic marker <span class="html-italic">Bax</span> were determined by qPCR. (<b>B</b>–<b>C</b>) The effects of BTL-I on the expression of the apoptosis markers Bax, Bcl-2, and Pro-Caspase 3 were determined by Western blotting. (<b>D</b>) Immunofluorescence staining for apoptosis was performed via the TUNEL assay. The results are expressed as the means ± SEMs. <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 compared with the control group; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 compared with the HS group.</p>
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<p>Effects of BTL-I on the ROS/PERK/CHOP signaling pathway in heat-stressed mice. (<b>A</b>–<b>C</b>) The effects of BTL-I on the expression of oxidative cytokines were determined by ELISA; (<b>D</b>,<b>E</b>) qPCR analysis of the expression of the PERK/CHOP signaling pathway markers <span class="html-italic">ATF4</span> and <span class="html-italic">CHOP</span>; and (<b>F</b>–<b>J</b>) Western blotting analysis of the expression of the PERK/CHOP signaling pathway markers p-PERK, PERK, p-eIF2α, eIF2α, ATF4, and CHOP; the results are expressed as the means ± SEMs. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 compared with the control group; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 compared with the HS group.</p>
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<p>Mouse experiment.</p>
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26 pages, 4377 KiB  
Article
Characteristics and Comparative Assessment of Flash Flood Hazard Evaluation Techniques: Insights from Wadi Haily Basin, Eastern Red Sea Coast, Saudi Arabia
by Bashar Bashir and Abdullah Alsalman
Water 2024, 16(24), 3634; https://doi.org/10.3390/w16243634 - 17 Dec 2024
Abstract
The Wadi Haily basin in southwest Saudi Arabia, which runs along the Red Sea coast, serves as an ideal natural laboratory for understanding flash flood dynamics in this region. However, limited morphometric and hydrological data are currently available in this area. This study [...] Read more.
The Wadi Haily basin in southwest Saudi Arabia, which runs along the Red Sea coast, serves as an ideal natural laboratory for understanding flash flood dynamics in this region. However, limited morphometric and hydrological data are currently available in this area. This study aims to analyze key morphometric effective parameters to examine and assess flash flood risk potential within the basin. Using remote sensing, GIS, geological, and topographical datasets, this research combines advanced modeling and GIS tools to produce detailed flood hazard maps and risk assessments. This study examines 15 sub-basins of varying sizes, characterized by primary stream orders ranging from 4th to 8th. Based on morphometric analysis, the basins are categorized by flood susceptibility: four basins have a low flood risk, five exhibit moderate risk, and six are highly susceptible to flooding. Key findings indicate that the study area features a vast drainage area, high grid cell values of the drainage frequency, moderate drainage density, elongated basin shapes, low infiltration rates, and long overland flow distances, all suggesting a heightened flood hazard. Additional indicators include high values in gradient ratios, slopes, ruggedness numbers, relief ratios, and basin relief, reinforcing the basin’s flash flood vulnerability. This study provides a comprehensive morphological framework that can support strategic flood management and hazard mitigation planning for the Wadi Haily region. Full article
20 pages, 6109 KiB  
Article
Maresin-like 1 Ameliorates Neuropathology of Alzheimer’s Disease in Brains of a Transgenic Mouse Model
by Pallavi Shrivastava, Yan Lu, Shanchun Su, Yuichi Kobayashi, Yuhai Zhao, Nathan Lien, Abdul-Razak Masoud, Walter J. Lukiw and Song Hong
Biomedicines 2024, 12(12), 2865; https://doi.org/10.3390/biomedicines12122865 - 17 Dec 2024
Abstract
(1) Background: Impeded resolution of inflammation contributes substantially to the pathogenesis of Alzheimer’s disease (AD); consequently, resolving inflammation is pivotal to the amelioration of AD pathology. This can potentially be achieved by the treatment with specialized pro-resolving lipid mediators (SPMs), which should resolve [...] Read more.
(1) Background: Impeded resolution of inflammation contributes substantially to the pathogenesis of Alzheimer’s disease (AD); consequently, resolving inflammation is pivotal to the amelioration of AD pathology. This can potentially be achieved by the treatment with specialized pro-resolving lipid mediators (SPMs), which should resolve neuroinflammation in brains. (2) Methods: Here, we report the histological effects of long-term treatment with an SPM, maresin-like 1 (MarL1), on AD pathogenesis in a transgenic 5xFAD mouse model. (3) Results: MarL1 treatment reduced Aβ overload, curbed the loss of neurons in brains especially cholinergic neurons associated with cleaved-caspase-3-associated apoptotic degeneration, reduced microgliosis and the pro-inflammatory M1 polarization of microglia, curbed the AD-associated decline in anti-inflammatory Iba1+Arg-1+-M2 microglia, inhibited phenotypic switching to pro-inflammatory N1 neutrophils, promoted the blood–brain barrier-associated tight-junction protein claudin-5 and decreased neutrophil leakage in 5xFAD brains, and induced the switch of neutrophils toward the inflammation-resolving N2 phenotype. (4) Conclusions: Long-term administration of MarL1 mitigates AD-related neuropathogenesis in brains by curbing neuroinflammation and neurodegeneration, based on the histological results. These findings provide preclinical leads and mechanistic insights for the development of MarL1 into an effective modality to ameliorate AD pathogenesis. Full article
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Figure 1

Figure 1
<p>MarL1 treatment ameliorated AD neuropathology in brains of 5xFAD mice. (<b>A</b>) Immunostaining of NeuN (green) and Amyloid-β<sub>1–42</sub> (red) in CA3 and dentate gyrus (DG) of hippocampus. White arrows mark some Aβ<sub>1–42</sub> deposition in hippocampal regions. Panels a–f: 10× magnification; scale bar: 180 μm. (<b>B</b>) Quantification of NeuN<sup>+</sup> and Amyloid-β<sub>1–42</sub><sup>+</sup> staining intensities of hippocampus (mean fluorescence intensity—MFI). Data are means ± SEM. Wildtype <span class="html-italic">n</span> = 6, 5xFAD <span class="html-italic">n</span> = 6, and 5xFAD+MarL1 <span class="html-italic">n</span> = 5. *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>MarL1 protected cholinergic neurons (ChAT<sup>+</sup>) and inhibited apoptotic cleaved caspase-3 activity in brains of 5xFAD mice. (<b>A</b>) Immunostaining of ChAT (green) and cleaved caspase-3 (red) in striatum (Panels a–c): 10× magnification; scale bar: 180 µm. White arrows mark cleaved caspase-3<sup>+</sup> cholinergic neurons in zoomed-in images (Panels d–f). Scale bar: 35 µm. (<b>B</b>) Quantification of ChAT and caspase-3 in striatum. Left: mean fluorescence intensity MFI for ChAT<sup>+</sup>; middle: MFI for cleaved caspase-3<sup>+</sup>; right: count of cells stained positive for both ChAT and cleaved-caspase-3. Data are means ± SEM. Wildtype <span class="html-italic">n</span> = 6, 5xFAD <span class="html-italic">n</span> = 6, and 5xFAD+MarL1 <span class="html-italic">n</span> = 5. *** <span class="html-italic">p</span> &lt; 0.001 and ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>MarL1 suppressed pro-inflammatory M1 phenotype polarization of microglia in brains of 5xFAD mice. (<b>A</b>) Immunostaining of microglia with Iba-1 (green) and CD68 (red) in CA1 region of hippocampus from 5xFAD transgenic mice (Panels a–c: 10× magnification; scale bar: 180 µm. Panels d–f: zoomed-in images; scale bar: 30 µm). White arrows mark Iba-1<sup>+</sup>CD68<sup>+</sup> microglia. (<b>B</b>) Quantification of Iba-1<sup>+</sup> and CD68<sup>+</sup> in hippocampus. Left: mean fluorescence intensity MFI of Iba-1<sup>+</sup>; middle: MFI of CD68<sup>+</sup>; right: count of microglia stained positive for both Iba-1<sup>+</sup> and CD68<sup>+</sup>. (<b>C</b>) Quantification of microglia based on phenotype characterization (ramified, partially ramified, partially amoeboid, amoeboid) in hippocampus. Data are means ± SEM. Wildtype <span class="html-italic">n</span> = 6, 5xFAD <span class="html-italic">n</span> = 6, and 5xFAD+MarL1 <span class="html-italic">n</span> = 5 for (<b>B</b>). Wildtype <span class="html-italic">n</span> = 6, 5xFAD <span class="html-italic">n</span> = 6, and 5xFAD+MarL1 <span class="html-italic">n</span> = 6 for (<b>C</b>). **** <span class="html-italic">p</span> &lt; 0.0001, *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01, and * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>MarL1 promoted anti-inflammatory M2 phenotype polarization of microglia in brains of 5xFAD mice. (<b>A</b>) Immunostaining of microglia with Iba-1 (green) and Arg1 (red) in cortex (Panels a–c: 20× magnification; scale bar: 90 µm. Panels d–f: zoomed-in images; scale bar: 30 µm). White arrows mark Iba1<sup>+</sup>Arg1<sup>+</sup> microglia. Red arrows mark microglial aggregation in cortex of 5xFAD mice. (<b>B</b>) Quantification of Iba-1 and Arg1 in cortex. Left: mean fluorescence intensity MFI of Iba1<sup>+</sup>; middle: MFI of Arg1<sup>+</sup>; right: count of microglia stained positive for both Iba1 and Arg1 in cortex. Data are means ± SEM. Wildtype <span class="html-italic">n</span> = 6, 5xFAD <span class="html-italic">n</span> = 6, and 5xFAD+MarL1 <span class="html-italic">n</span> = 5. *** <span class="html-italic">p</span> &lt; 0.001 and ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>MarL1 attenuated the AD-associated compromise of blood–brain barrier tight-junctions as well as neutrophil infiltration into brains of 5xFAD mice. (<b>A</b>) Immunostaining of Gr-1 (green) for neutrophils and claudin-5 (red) for tight-junctions of the vasculatures in cortex. Panels a–c show images from cortex (4× magnification; scale bar: 460 µm). Panels d–f show zoomed-in images; scale bar: 65 µm. White arrows mark some Gr-1<sup>+</sup> cells outside the vasculature in parenchyma in zoomed-in images. Yellow arrows mark some claudin-5<sup>+</sup> vasculatures. Neutrophil swarming is evident in Panels b and e. (<b>B</b>) Quantification of Gr-1<sup>+</sup> and claudin-5<sup>+</sup> in MFI in cortex. Data are means ± SEM. Wildtype <span class="html-italic">n</span> = 6, 5xFAD <span class="html-italic">n</span> = 6, and 5xFAD+MarL1 <span class="html-italic">n</span> = 5. *** <span class="html-italic">p</span> &lt; 0.001 and * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>MarL1 treatment suppressed pro-inflammatory N1 polarization of neutrophils infiltrated into AD-pathogenic brains in 5xFAD mice. (<b>A</b>) Immunostaining of Gr-1 (green) for neutrophils and iNOs (red), an inflammatory marker. Panels a–c show hippocampus (4× magnification; scale bar: 460 µm). Panels d–f show zoomed-in images; scale bar: 40 µm. White arrows mark some Gr-1<sup>+</sup>iNOs<sup>+</sup> cells and yellow arrows mark only Gr-1-positive cells in zoomed-in panels. (<b>B</b>) Quantification of Gr-1<sup>+</sup> and iNOs<sup>+</sup> in hippocampus. Left: MFI of Gr-1<sup>+</sup>; middle: MFI of iNOs<sup>+</sup>; right: Pearson’s coefficient for quantification of co-localization of Gr-1 and iNOs. Data are means ± SEM. Wildtype <span class="html-italic">n</span> = 6, 5xFAD <span class="html-italic">n</span> = 6, and 5xFAD+MarL1 <span class="html-italic">n</span> = 5. *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt;0.01, and * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>MarL1 treatment induced anti-inflammatory N2 phenotypic polarization of neutrophils infiltrated into AD-pathogenic brains in 5xFAD mice. (<b>A</b>) Immunostaining of Gr-1 (green) for neutrophils and Arg1 (red), an anti-inflammatory marker. Panels a–c show hippocampus (4× magnification, scale bar: 460 µm). Panels d–f show zoomed-in images; scale bar: 40 µm. White arrows mark Gr-1<sup>+</sup> cells and yellow arrows mark Gr-1<sup>+</sup>Arg1<sup>+</sup> cells in zoomed-in panels. (<b>B</b>) Quantification of Gr-1<sup>+</sup> and Arg1<sup>+</sup> in hippocampus. Left: MFI of Gr-1<sup>+</sup>; middle: MFI of Arg1<sup>+</sup>; right: Pearson’s coefficient for quantification of co-localization of Gr-1 and Arg1. Data are means ± SEM. Wildtype <span class="html-italic">n</span> = 6, 5xFAD <span class="html-italic">n</span> = 6, and 5xFAD+MarL1 <span class="html-italic">n</span> = 5. *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01, and * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>A graphic summary.</p>
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26 pages, 6218 KiB  
Article
Revealing the Mechanism of Hemerocallis citrina Baroni in Depression Treatment Through Integrated Network Pharmacology and Transcriptomic Analysis
by Shan Gao, Jihui Lu, Yixiao Gu, Yaozhi Zhang, Cheng Wang, Feng Gao, Ziqi Dai, Shujing Xu, Jindong Zhang, Yuqin Yang and Haimin Lei
Pharmaceuticals 2024, 17(12), 1704; https://doi.org/10.3390/ph17121704 - 17 Dec 2024
Abstract
Background/Objectives: Hemerocallis citrina Baroni (HCB) is a traditional herb for the treatment of depression in China. However, the active constituents and the underlying mechanisms of its antidepressant effects remain unclear. The aim of this study was to identify the bioactive constituents of [...] Read more.
Background/Objectives: Hemerocallis citrina Baroni (HCB) is a traditional herb for the treatment of depression in China. However, the active constituents and the underlying mechanisms of its antidepressant effects remain unclear. The aim of this study was to identify the bioactive constituents of HCB and elucidate its underlying mechanism for the treatment of depression. Methods: The constituents of HCB were systematically analyzed using UHPLC-Q-Orbitrap HRMS. Its antidepressant effect was evaluated by chronic unpredictable mild stress (CUMS)-induced depression. The mechanism of HCB in treating depression was investigated through network pharmacology and molecular docking. Subsequently, its potential mechanism for the treatment of depression was carried out by RNA sequencing. Finally, the mechanism was further verified by Western blot. Results: A total of 62 chemical constituents were identified from HCB using UHPLC-Q-Orbitrap HRMS, including 17 flavonoids, 11 anthraquinones, 11 alkaloids, 10 caffeoylquinic acid derivatives, five phenolic acids, five triterpenoids, and three phenylethanosides, 13 of which were identified as potential active constituents targeting 49 depression-associated proteins. Furthermore, HCB was found to significantly reduce cognitive impairment, anxiety-like behavior, and anhedonia-like behavior. The expression levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and brain-derived neurotrophic factor (BDNF) were elevated in the hippocampal CA3 region. Results from network pharmacology and transcriptomics indicated that the PI3K/Akt/CREB signaling pathway is essential for the therapeutic effects of HCB on depression. Research in the field of molecular biology has conclusively demonstrated that HCB is associated with an increase in the expression levels of several important proteins. Specifically, there was a notable upregulation of phosphorylated PI3K (p-PI3K) relative to its unphosphorylated form PI3K, as well as an elevation in the ratio of phosphorylated Akt (p-Akt) to total Akt. Additionally, the study observed increased levels of phosphorylated CREB (p-CREB) compared to its unphosphorylated CREB. Conclusions: This study provides compelling evidence that HCB possesses the ability to mitigate the symptoms of depression through its influence on the PI3K/Akt/CREB signaling pathway. HCB could be developed as a promising therapeutic intervention for individuals struggling with depression, offering new avenues for treatment strategies that target this particular signaling mechanism. Full article
(This article belongs to the Special Issue Discovery of Novel Antidepressants and Anxiolytics)
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Graphical abstract

Graphical abstract
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<p>Mass spectrogram of HCB. (<b>A</b>) TICC of HCB obtained in ESI+ mode. Product ion spectra of (<b>B</b>) kaempferol-3-rutinoside. (<b>C</b>) quercetin. (<b>D</b>) rutin. (<b>E</b>) kwanzoquinone G. (<b>F</b>) rhein. (<b>G</b>) gallic acid. (<b>H</b>) clionasterol. (<b>I</b>) adenosine.</p>
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<p>HCB improved CUMS mice depression-like behaviors. (<b>A</b>) Schematic diagram of experimental design. (<b>B</b>) Representative images of movement trajectory. (<b>C</b>) Total distance within 5 min in the OFT (<span class="html-italic">n</span> = 8). (<b>D</b>) Time spent in the central area in the OFT (<span class="html-italic">n</span> = 8). (<b>E</b>) Not moving time in the OFT within 5 min (<span class="html-italic">n</span> = 8). (<b>F</b>) Immobility time in the FST within 4 min (<span class="html-italic">n</span> = 8). (<b>G</b>) Changes in precent of sucrose preference in the SPT (<span class="html-italic">n</span> = 8). (<b>H</b>) The secretion levels of 5-hydroxytryptamine (<span class="html-italic">n</span> = 3). (<b>I</b>) The secretion levels of dopamine (<span class="html-italic">n</span> = 3). (<b>J</b>) The secretion levels of BDNF (<span class="html-italic">n</span> = 3). (<b>K</b>) The number of Nissl bodies in the hippocampal CA3 regions (<span class="html-italic">n</span> = 3). (<b>L</b>) Representative pictures of Nissl staining in the hippocampi. Data are presented as mean ± SEM, <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. control group (C-group); * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. model group (M-group).</p>
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<p>Analysis results of network pharmacology and molecular docking. (<b>A</b>) Venn mapping of HCB on depression. (<b>B</b>) PPI networks of candidate targets. (<b>C</b>) The network construction of compounds–targets–diseases. (<b>D</b>) GO enrichment analysis. (<b>E</b>) KEGG pathway analysis. (<b>F</b>) Molecular docking diagram of active constitutes and potential targets.</p>
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<p>RNA sequencing analysis of hippocampus. (<b>A</b>) Volcano map of DEGs. (<b>B</b>) Hierarchical clustering analysis of DEGs. (<b>C</b>) Functional annotation analysis of GO using DEGs. (<b>D</b>) Functional enrichment analysis of KEGG using DEGs.</p>
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<p>HCB regulated PI3K/Akt/CREB signaling pathway (<b>A</b>) Representative protein bands of PI3K, p-PI3K, Akt, p-Akt, CREB, and p-CREB in hippocampal. Statistical graphs of relative protein expression of ratio of p-PI3K/PI3K (<b>B</b>), PI3K/GAPDH (<b>C</b>), p-Akt/Akt (<b>D</b>), Akt/GAPDH (<b>E</b>), p-CREB/CREB (<b>F</b>), and CREB/GAPDH (<b>G</b>). Data are presented as mean ± SEM, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01, <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. control group (C-group); * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 vs. model group (M-group).</p>
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<p>Identification of antidepressant constitutes in HCB and its underlying mechanism on the treatment of depression.</p>
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16 pages, 798 KiB  
Article
Efficacy of Hovenia dulcis Fruit Extract in Hangover Mitigation: Double-Blind Randomized Clinical Evaluation
by Dong Hyun Paik, Ki Won Lee, Youn Young Shim, Martin J. T. Reaney, Ilbum Park, Sang-Hun Lee, Jong-Yul Park, Euddeum Park, Sung-Bum Lee, In Ah Kim, Guangpeng Xu, Ji Youn Hong and Young Jun Kim
Foods 2024, 13(24), 4084; https://doi.org/10.3390/foods13244084 - 17 Dec 2024
Abstract
The fruit of Hovenia dulcis Thunb. (HD) is renowned for its medicinal properties and is rich in bioactive compounds, traditionally used in East Asian medicine as a natural antidote for alcohol intoxication. A randomized, double-blind, crossover, placebo (PLA)-controlled clinical trial was conducted to [...] Read more.
The fruit of Hovenia dulcis Thunb. (HD) is renowned for its medicinal properties and is rich in bioactive compounds, traditionally used in East Asian medicine as a natural antidote for alcohol intoxication. A randomized, double-blind, crossover, placebo (PLA)-controlled clinical trial was conducted to compare the effects of beverages containing 0.475% HD (HDB), HD combined with 0.1% Pueraria lobata extract (HDPB), and HD combined with 0.02% glutathione yeast extract (HDGB) with the PLA on the symptoms of a hangover. Subjects (n = 30) were randomized into six test groups consuming three beverages, including the PLA. After ingestion, blood alcohol and blood acetaldehyde concentrations were measured at 0, 0.25, 0.5, 1, 2, 4, 6, and 15 h post-alcohol consumption. No significant differences in hematology tests and vital signs were observed amongst the treatment groups; however, at 0.5 and 6 h, the blood alcohol concentrations of the HDB and HDPB groups were significantly lower compared to the PLA group (p < 0.05). Additionally, the blood acetaldehyde concentrations in the HDPB group showed significantly lower values than the PLA after 6 h (p < 0.05). These findings suggest that HD may aid in alcohol detoxification and limit acetaldehyde accumulation. This indicates the potential for HD as a functional food ingredient for alleviating hangover symptoms. Full article
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<p>Overview of human clinical trial.</p>
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<p>A flow chart illustrating the selection and allocation of participants in this study. Thirty eligible subjects were randomized to one of the six groups, followed by a one-week washout period, and then crossed over to the other group. All subjects completed the study.</p>
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<p>Effect of samples and PLA on (<b>A</b>) blood alcohol and (<b>B</b>) acetaldehyde concentrations after alcohol consumption at different time points (0, 0.25, 0.5, 1, 2, 4, 6, and 15 h). Group comparisons were conducted using <span class="html-italic">p</span>-values derived from either the two-sample <span class="html-italic">t-</span>test (T) or Wilcoxon rank sum test (W). * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Effect of samples and PLA on (<b>A</b>) blood alcohol and (<b>B</b>) acetaldehyde concentrations after alcohol consumption at different time points (0, 0.25, 0.5, 1, 2, 4, 6, and 15 h). Group comparisons were conducted using <span class="html-italic">p</span>-values derived from either the two-sample <span class="html-italic">t-</span>test (T) or Wilcoxon rank sum test (W). * <span class="html-italic">p</span> &lt; 0.05.</p>
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25 pages, 2221 KiB  
Systematic Review
A Systematic Review of BIM-Based Life Cycle Sustainability Assessment for Buildings
by Ileana Berges-Alvarez, Alejandro Martínez-Rocamora and Madelyn Marrero
Sustainability 2024, 16(24), 11070; https://doi.org/10.3390/su162411070 - 17 Dec 2024
Abstract
The construction industry has enormous impacts on the three dimensions of sustainability: environmental, economic, and social. To mitigate these impacts, several researchers have explored a variety of methods that link Building Information Modeling (BIM) with methodologies for a holistic evaluation of sustainability, such [...] Read more.
The construction industry has enormous impacts on the three dimensions of sustainability: environmental, economic, and social. To mitigate these impacts, several researchers have explored a variety of methods that link Building Information Modeling (BIM) with methodologies for a holistic evaluation of sustainability, such as Life Cycle Sustainability Assessment (LCSA). However, the complete integration of BIM-LCSA still remains unresolved, with a series of challenges that must be overcome. Consequently, the aim of this article is to identify the advances and challenges of BIM-LCSA integration focused on buildings through a literature review of the existing solutions presented by researchers worldwide. The PRISMA 2020 protocol is used. A total of 135 articles published between 2010–2023 are reviewed for bibliometric analysis. Furthermore, an exhaustive analysis of the case studies is carried out, by taking into account the structure proposed by ISO 14040. The authors identify a gap in the literature mainly regarding the full integration of the three dimensions with BIM that facilitates a simultaneous on-the-air assessment, in addition to the lack of a standardized LCSA method of calculation. Full article
(This article belongs to the Section Green Building)
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Figure 1
<p>Summary scheme of the review scope, methodology, and criteria.</p>
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<p>(I) Year of publication per source type and integration type. The gray line represents the combined tendency of all the publications.</p>
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<p>Summary of the definitions of the objective and scope by the different articles of the SLR are group per (<b>a</b>) stage of application; (<b>b</b>) building typology; (<b>c</b>) functional unit; (<b>d</b>) lifespan in years; (<b>e</b>) building life cycle phase; and (<b>f</b>) level of development.</p>
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<p>Integration approaches and software used in the research reviewed.</p>
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<p>PRISMA flow diagram.</p>
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11 pages, 4258 KiB  
Article
The Effect of Milk-Derived Extracellular Vesicles on Intestinal Epithelial Cell Proliferation
by Shimon Reif, Liron Birimberg-Schwartz, Myriam Grunewald, Deborah Duran, Naama Sebbag-Sznajder, Tirtsa Toledano, Mirit Musseri and Regina Golan-Gerstl
Int. J. Mol. Sci. 2024, 25(24), 13519; https://doi.org/10.3390/ijms252413519 - 17 Dec 2024
Abstract
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammation disorder of the gastrointestinal tract characterized by disrupted intestinal epithelial barrier function. Despite advances in treatment, including biological agents, achieving sustained remission remains challenging for many patients with IBD. This highlights the urgent need [...] Read more.
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammation disorder of the gastrointestinal tract characterized by disrupted intestinal epithelial barrier function. Despite advances in treatment, including biological agents, achieving sustained remission remains challenging for many patients with IBD. This highlights the urgent need for novel therapeutic strategies. Milk-derived extracellular vesicles (MDEs) have emerged as a promising therapeutic option. In this study, we isolated and characterized MDEs and evaluated their effects on the function of intestinal epithelial cells (IECs). Using a murine model of Dextran Sulfate Sodium (DSS)-induced colitis, we observed that MDEs significantly ameliorated disease symptoms. The upregulation of β-catenin, a crucial mediator of Wnt signaling, in colonic tissues suggests that MDEs may facilitate epithelial regeneration and restore barrier function. In patient-derived colon organoids (PDCOs), MDEs were internalized and modulated the expression of key signaling molecules, such as the upregulation of β-catenin, cyclin D1, and the proliferation marker Ki67, indicating their potential to promote IEC proliferation and intestinal barrier repair. Importantly, MDEs demonstrated selective activity by downregulating β-catenin and cyclin D1 in colon cancer cells, leading to reduced proliferation. This selectivity indicates a dual therapeutic potential of MDEs for promoting healthy IEC proliferation while potentially mitigating malignancy risks. Full article
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Figure 1
<p>Characterization of MDEs. (<b>A</b>) Transmission electron microscopy (TEM) with negative staining was used to visualize MDEs. (<b>B</b>) The particle size distribution of isolated MDEs was determined by dynamic light scattering (DLS), with results performed in triplicate indicating an average diameter of 158.3 nm. (<b>C</b>) Western blot analysis was performed to assess the protein expression of Cluster of Differentiation 81 (CD81). (<b>D</b>) Quantitative real-time PCR (qRT-PCR) was used to measure the expression of abundant microRNA (miRNA) in MDEs. MiRNA expression was calculated using the 2<sup>−ΔΔCT</sup> method and normalized to RNU6. miR-148 (148), miR-21 (21), Let-7a (7A), miR-29b (29B), miR-22 (22), miR223 (223), miR-26a (26), miR-30 (30), miR-320 (320), miR-375 (375), miR-27B (27B), miR-378 (378) and miR-146b (146B).</p>
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<p>Effects of MDEs on a dextran sulfate sodium (DSS)-induced colitis model in mice. MDEs were orally administrated to mice with DSS-induced colitis. (<b>A</b>) Body weight of control (CONT) mice, colitic mice treated with (DSS + MDE), and untreated colitic mice (DSS). (<b>B</b>) Disease activity score in CONT, DSS + MDE, and DSS mice. (<b>C</b>) Colon length in control CONT, DSS + MDE, and DSS mice. (<b>D</b>) β-catenin protein expression in the colon of CONT, DSS + MDE, and PBS (DSS) mice. Protein expression was determined by Western blot, with β-actin as the loading control. (<b>E</b>) Quantification of β-catenin protein levels was performed using the ImageJ software, (U. S. National Institutes of Health, Bethesda, Maryland, USA, <a href="https://imagej.net/ij/" target="_blank">https://imagej.net/ij/</a>). Data are presented as mean ± SEM, n = 8 per group, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001 (Mann–Whitney test).</p>
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<p>MDE uptake and miRNA expression in intestinal organoids. (<b>A</b>) Fluorescent images of 3D patient-derived colon organoid (PDCO) cultures incubated with labeled cow MDEs (0.1 mg/mL) were obtained by fluorescence microscopy. (<b>B</b>) Expression of let-7 and miRNA-148 in MDE-treated (0.1 mg/mL) (MDE) and untreated (PBS) PDCOs were assessed by qRT-PCR. MiRNA expression was calculated using the 2<sup>−ΔΔCT</sup> method and normalized to RNU6. (<b>C</b>) <span class="html-italic">DNMT1</span> expression in MDE-treated (MDE) and untreated (PBS) PDCOs was analyzed by qRT-PCR. mRNA expression was calculated using the 2<sup>−ΔΔCT</sup> method and normalized to GAPDH. Data are presented as mean ± SEM. ** <span class="html-italic">p</span> &lt; 0.01. Scale bar: 100 μm.</p>
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<p>The effect of MDE treatment on β-catenin and <span class="html-italic">cyclin D1</span> expression in patient-derived colon organoids (PDCOs). (<b>A</b>) Immunostaining analysis of PDCOs from IBD patients treated with 0.1 mg/mL MDE (MDE) or untreated (PBS), showing β-catenin expression. Representative images from fluorescent microscopy. Scale bar: 0.1 mm. (<b>B</b>) Expression of cyclin D1 in MDE-treated (MDE) and untreated (PBS) PDCOs was analyzed by qRT-PCR. Values were calculated using the 2<sup>−ΔΔCT</sup> method and normalized to <span class="html-italic">GAPDH</span>. Data are presented as mean ± SEM. ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>The effect of MDE treatment on proliferation of patient-derived colon organoids (PDCOs). Representative images from immunostaining analysis of PDCOs from IBD patients treated with 0.1 mg/mL MDE (MDE) or untreated (CONT) showing proliferative cells (Ki67). Images were acquired using fluorescent microscopy. Scale bar: 0.1 mm.</p>
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<p>The effect of MDEs on human colon tumor cells (LS123). (<b>A</b>) Expression of β-catenin and cyclin D1 protein in LS123 cells incubated with MDEs at two different concentrations (0.1 and 0.01 mg/mL MDE) or without MDEs (CONT). Protein expression was determined by Western blot, with β-actin used as the loading control. (<b>B</b>) LS123 cells grown in 0% fetal calf serum (FCS) and incubated with MDEs at two different concentrations (0.1 and 0.01 mg/mL MDE) or without (CONT) were examined using the CCK-8 assay to assess cell growth. Error bars represent SD (n = 4). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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Article
Improving Dementia Home Caregiving and Restructuring the Dementia Narrative Through Creating a Graphic Memoir and Engaging in a Psychoanalytic Narrative Research Method
by Carol Nash
J. Ageing Longev. 2024, 4(4), 464-488; https://doi.org/10.3390/jal4040034 - 17 Dec 2024
Abstract
Informal dementia home caregiving is viewed negatively by society and can result in caregiver depression and anxiety from burnout, potentially compromising caregiving. Caregiver creation of a graphic memoir may help to mitigate the negative dementia narrative while engaging in it, and a psychoanalytic [...] Read more.
Informal dementia home caregiving is viewed negatively by society and can result in caregiver depression and anxiety from burnout, potentially compromising caregiving. Caregiver creation of a graphic memoir may help to mitigate the negative dementia narrative while engaging in it, and a psychoanalytic narratology method may reduce experienced depression and anxiety associated with burnout. This investigation examines writing, illustrating, and publishing a graphic memoir by one informal dementia home caregiver. As the mother of the illustrator and the editor and publisher of this graphic memoir, I provide the perspective of this investigation based on communications with the author and illustrator. My historical analysis, in which the author participated, represents psychoanalytic narrative research, serving as the historical method. The effects of writing, illustrating, and publishing the graphic memoir were able to reduce the informal dementia home caregivers’ symptoms during the entire process and extend the effect of this endeavor until the death of the mother. Engaging in the psychoanalytic narrative research process was additionally effective in this regard. The outcomes demonstrate the viability of writing and illustrating a publishable graphic memoir for other informal dementia home caregivers and the possibility of it and the narrative research method to help decrease their depression and anxiety regarding burnout. Full article
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Graphical abstract

Graphical abstract
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<p>Cover of <span class="html-italic">Keeper of the Clouds</span> [<a href="#B72-jal-04-00034" class="html-bibr">72</a>] published by Tampold Publishing, a company owned and operated by me, the author of this article.</p>
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<p>Cover of <span class="html-italic">The Hallway Closet</span> [<a href="#B113-jal-04-00034" class="html-bibr">113</a>] published by Tampold Publishing, a company owned and operated by me, the author of this article.</p>
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<p>Bottom half of page 5 of <span class="html-italic">Keeper of the Clouds</span> [<a href="#B72-jal-04-00034" class="html-bibr">72</a>] published by Tampold Publishing, a company owned and operated by me, the author of this article.</p>
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<p>(<b>a</b>,<b>b</b>) Bottom half of the original page 3 of <span class="html-italic">Keeper of the Clouds</span> is on the left, and the final version of the bottom of page 3 (published by Tampold Publishing, a company owned and operated by me, the author of this article), is on the right [<a href="#B72-jal-04-00034" class="html-bibr">72</a>].</p>
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<p>The bottom half of page 12 of Keeper of the Clouds [<a href="#B61-jal-04-00034" class="html-bibr">61</a>]—a publication of Tampold Publishing, a company owned and operated by me, the author of this article.</p>
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