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16 pages, 1544 KiB  
Review
Determinants of Photodynamic Therapy Resistance in Cancer Cells
by Alicja Dąbrowska, Jakub Mastalerz, Bartosz Wilczyński, Beata Osiecka and Anna Choromańska
Int. J. Mol. Sci. 2024, 25(22), 12069; https://doi.org/10.3390/ijms252212069 - 10 Nov 2024
Viewed by 329
Abstract
Photodynamic therapy (PDT) has emerged as a promising therapeutic approach owing to its non-invasive nature and minimal toxicity. PDT involves the administration of a photosensitizing agent (PS), which, upon light activation, induces a photodynamic reaction (PDR), leading to targeted cell destruction. However, developing [...] Read more.
Photodynamic therapy (PDT) has emerged as a promising therapeutic approach owing to its non-invasive nature and minimal toxicity. PDT involves the administration of a photosensitizing agent (PS), which, upon light activation, induces a photodynamic reaction (PDR), leading to targeted cell destruction. However, developing resistance to PDT poses a significant challenge to its effectiveness. Various factors, including properties and administration of PSs, mediate this resistance. Despite the widespread use of substances like 5-aminolevulinic acid (5-ALA) and protoporphyrin, their efficacy is limited due to restricted tumor penetration and a lack of tumor targeting. To address these limitations, nano-delivery techniques and newer PSs like Aza-BODIPY and its derivatives, which offer enhanced tissue penetration, are being explored. In this paper, we provide an overview of resistance mechanisms in PDT and discuss novel methods, substances, and technologies to overcome resistance to improve clinical outcomes in tumor treatment. Full article
(This article belongs to the Special Issue The Roles of Photodynamic Therapy in Tumors and Cancers)
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<p>Mechanisms of cancer cell resistance to photodynamic therapy [<a href="#B1-ijms-25-12069" class="html-bibr">1</a>,<a href="#B2-ijms-25-12069" class="html-bibr">2</a>,<a href="#B3-ijms-25-12069" class="html-bibr">3</a>,<a href="#B4-ijms-25-12069" class="html-bibr">4</a>,<a href="#B5-ijms-25-12069" class="html-bibr">5</a>,<a href="#B6-ijms-25-12069" class="html-bibr">6</a>,<a href="#B9-ijms-25-12069" class="html-bibr">9</a>].</p>
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<p>P-gp inhibitors, like verapamil, lead to an increased photosensitizer concentration inside the cell which contributes to enhanced photodamage [<a href="#B10-ijms-25-12069" class="html-bibr">10</a>,<a href="#B11-ijms-25-12069" class="html-bibr">11</a>,<a href="#B12-ijms-25-12069" class="html-bibr">12</a>].</p>
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<p>The targeted structure can determine PDT’s effect. PDT directed at anti-apoptotic proteins leads to cell death, yet damage to cell membranes evokes the opposite effect [<a href="#B27-ijms-25-12069" class="html-bibr">27</a>,<a href="#B28-ijms-25-12069" class="html-bibr">28</a>,<a href="#B29-ijms-25-12069" class="html-bibr">29</a>].</p>
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<p>The effect of nitric oxide produced as a result of photodynamic therapy (PDT) on cancer cells, including bystander cells [<a href="#B47-ijms-25-12069" class="html-bibr">47</a>,<a href="#B48-ijms-25-12069" class="html-bibr">48</a>,<a href="#B49-ijms-25-12069" class="html-bibr">49</a>,<a href="#B50-ijms-25-12069" class="html-bibr">50</a>,<a href="#B51-ijms-25-12069" class="html-bibr">51</a>,<a href="#B52-ijms-25-12069" class="html-bibr">52</a>].</p>
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<p>The dual role of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) in the development of resistance to PDT [<a href="#B64-ijms-25-12069" class="html-bibr">64</a>,<a href="#B65-ijms-25-12069" class="html-bibr">65</a>,<a href="#B66-ijms-25-12069" class="html-bibr">66</a>,<a href="#B67-ijms-25-12069" class="html-bibr">67</a>].</p>
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28 pages, 18631 KiB  
Article
Analysis of Paddy Field Changes (1989–2021) Using Landsat Images and Flooding-Assisted MLC in an Urbanizing Tropical Watershed, Vientiane, Lao PDR
by Iep Keovongsa, Atiqotun Fitriyah, Fumi Okura, Keigo Noda, Koshi Yoshida, Keoduangchai Keokhamphui and Tasuku Kato
Sustainability 2024, 16(22), 9776; https://doi.org/10.3390/su16229776 - 9 Nov 2024
Viewed by 693
Abstract
Paddy fields are essential for food security and sustaining global dietary needs, yet urban expansion often encroaches on agricultural lands. Analyzing paddy fields and land use/land cover changes over time using satellite images provides critical insights for sustainable food production and balanced urban [...] Read more.
Paddy fields are essential for food security and sustaining global dietary needs, yet urban expansion often encroaches on agricultural lands. Analyzing paddy fields and land use/land cover changes over time using satellite images provides critical insights for sustainable food production and balanced urban growth. However, mapping the paddy fields in tropical monsoon areas presents challenges due to persistent weather interference, monsoon-submerged fields, and a lack of training data. To address these challenges, this study proposed a flooding-assisted maximum likelihood classification (F-MLC) method. This approach utilizes accurate training datasets from intersecting flooded paddy field maps from the rainy and dry seasons, combined with the Automated Water Extraction Index (AWEI) to distinguish natural water bodies. The F-MLC method offers a robust solution for accurately mapping paddy fields and land use changes in challenging tropical monsoon climates. The classified images for 1989, 2000, 2013, and 2021 were produced and categorized into the following five major classes: urban areas, vegetation, paddy fields, water bodies, and other lands. The paddy field class derived for each year was validated using samples from various sources, contributing to the overall accuracies ranging from 83.6% to 90.4%, with a Kappa coefficient of between 0.80 and 0.88. The study highlights a significant decrease in paddy fields, while urban areas rapidly increased, replacing 23% of paddy fields between 1989 and 2021 in the watershed. This study demonstrates the potential of the F-MLC method for analyzing paddy fields and other land use changes over time in the tropical watershed. These findings underscore the urgent need for robust policy measures to protect paddy fields by clearly defining urban expansion boundaries, prioritizing paddy field preservation, and integrating these green spaces into urban development plans. Such measures are vital for ensuring a sustainable local food supply, promoting balanced urban growth, and maintaining ecological balance within the watershed. Full article
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<p>Location map of the study area.</p>
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<p>Referenced daily rainfall: 1989 (<b>a</b>), 2000 (<b>b</b>), 2013 (<b>c</b>), 2021 (<b>d</b>), and rice crop calendar in Laos (<b>e</b>) modified from FAO [<a href="#B65-sustainability-16-09776" class="html-bibr">65</a>].</p>
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<p>Methodological flowchart for detecting paddy fields and other classes.</p>
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<p>The initial paddy field maps for 1989 (<b>a</b>); 2000 (<b>b</b>); 2013 (<b>c</b>), and 2021 (<b>d</b>).</p>
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<p>The ground-truth data samples in the MHR watershed from field survey in 2022 and 2023.</p>
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<p>Spatial explanatory factors, road distance (m) for 2010 (<b>a</b>) and 2021 (<b>b</b>), and population density (person/km<sup>2</sup>) for 2015 (<b>c</b>) and the projection for 2020 (<b>d</b>).</p>
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<p>Classified LULC maps of the MHR watershed in 1989, 2000, 2013, and 2021.</p>
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<p>Change in Areas of LULC Classes in the MHR Watershed from 1989 to 2021.</p>
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<p>Spatial comparison and percent coverage: (<b>a</b>) 2000, (<b>b</b>) 2013, and (<b>c</b>) 2021 show spatial overlay of paddy fields between F-MLC and MAF’s maps; (<b>a1</b>–<b>c1</b>) provide detailed zoom-ins of the spatial overlay; (<b>a2</b>–<b>c2</b>) indicate the percent coverage of both maps in the watershed.</p>
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<p>Conversion trends of paddy fields in the MHR watershed (PF—paddy fields, UB—urban area, VE—vegetation, WB—water bodies, OL—other land (<b>left</b>). Demand and harvested rice (<b>right</b>).</p>
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<p>The boundary of the permitted areas for economic and urban development in Vientiane lies within the MHR watershed. “PF” refers to the paddy field areas.</p>
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<p>Observed points and Google Earth imagery: (<b>a1</b>–<b>c1</b>) show the zoomed-in sections of the classified image from 2021. (<b>a2</b>) shows that fallow paddy fields along the roadside were incorrectly classified as active paddy fields. (<b>b2</b>,<b>c2</b>) demonstrate the presence of rainwater storage ponds on paddy fields, as captured by Google Earth imagery.</p>
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<p>Detail of paddy field changes in peri-urban areas. The upper panels display imagery from Google Earth Pro for the clearest and most relevant time periods. The lower panels show the paddy fields affected by urban expansion from 2000 to 2021.</p>
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<p>Spatial conversion of paddy fields (PF) from 1989 to 2021: (<b>a</b>,<b>b</b>) provide zoomed-in views of PF conversion into urban areas near major roads.</p>
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<p>Band composition for identifying flooding/transplanting tone over the study area in July 1989.</p>
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33 pages, 9060 KiB  
Article
A Q-Learning-Based Approach to Design an Energy-Efficient MAC Protocol for UWSNs Through Collision Avoidance
by Qiao Gang, Wazir Ur Rahman, Feng Zhou, Muhammad Bilal, Wasiq Ali, Sajid Ullah Khan and Muhammad Ilyas Khattak
Electronics 2024, 13(22), 4388; https://doi.org/10.3390/electronics13224388 - 8 Nov 2024
Viewed by 360
Abstract
Deploying and effectively utilizing wireless sensor networks (WSNs) in underwater habitats remains a challenging task. In underwater wireless sensors networks (UWSNs), the availability of a continuous energy source for communicating with nodes is either very costly or is prohibited due to the marine [...] Read more.
Deploying and effectively utilizing wireless sensor networks (WSNs) in underwater habitats remains a challenging task. In underwater wireless sensors networks (UWSNs), the availability of a continuous energy source for communicating with nodes is either very costly or is prohibited due to the marine life law enforcement agencies. So, in order to address this issue, we present a Q-learning-based approach to designing an energy-efficient medium access control (MAC) protocol for UWSNs through collision avoidance. The main goal is to prolong the network’s lifespan by optimizing the communication methods, specifically focusing on improving the energy efficiency of the MAC protocols. Factors affecting the energy consumption in communication are adjustments to the interference ranges, i.e., changing frequencies repeatedly to obtain optimal communication; data packet retransmissions in case of a false acknowledgment; and data packet collision occurrences in the channel. Our chosen protocol stands out by enabling sensor (Rx) nodes to avoid collisions without needing extra communication or prior interference knowledge. According to the results obtained through simulations, our protocol may increase the network’s performance in terms of network throughput by up to 23% when compared to benchmark protocols depending on the typical traffic load. It simultaneously decreases end-to-end latency, increases the packet delivery ratio (PDR), boosts channel usage, and lessens packet collisions by over 38%. All these gains result in minimizing the network’s energy consumption, with a proportional gain. Full article
(This article belongs to the Special Issue New Advances in Underwater Communication Systems)
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<p>Detailed overview of the designed paradigm.</p>
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<p>Example of a collision between system clusters.</p>
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<p>Example of transmitting data packets with collision or no collision at the same and different times.</p>
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<p>Tackling the hidden and exposed node challenges in UWCNs.</p>
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<p>Multi-cluster underwater wireless sensor network.</p>
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<p>Flow chart for our proposed system communication performance.</p>
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<p>Average network throughput vs. no. of nodes.</p>
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<p>Network throughput vs. traffic load.</p>
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<p>Average network delay vs. number of nodes.</p>
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<p>Different traffic loads vs. average delay.</p>
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<p>Average traffic time vs. no of nodes.</p>
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<p>Comparison of channel utilization and slot size.</p>
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<p>Comparison of channel utilization and slot size.</p>
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<p>Comparison of Q-value and action.</p>
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<p>Comparison of channel utilization and episode.</p>
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<p>PDR vs. average traffic load.</p>
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<p>PDR vs. number of nodes.</p>
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<p>Collision vs. avg. traffic load.</p>
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<p>Energy consumption vs. number of nodes.</p>
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<p>Energy consumption vs. offered load.</p>
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<p>Energy efficiency vs. avg. traffic load.</p>
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<p>Evaluation of the convergence values for Q-learning algorithm.</p>
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<p>Channel utilization vs. time blocks.</p>
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<p>Channel utilization vs. number of nodes.</p>
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<p>Energy consumption vs. number of nodes.</p>
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18 pages, 5059 KiB  
Article
Batzelladine D, a Marine Natural Product, Reverses the Fluconazole Resistance Phenotype Mediated by Transmembrane Transporters in Candida albicans and Interferes with Its Biofilm: An In Vitro and In Silico Study
by Levy T. S. Domingos, Daniel C. de Moraes, Mário F. C. Santos, José A. R. Curvelo, Brayan Bayona-Pacheco, Edgar A. Marquez, Anthony W. B. Martinez, Roberto G. S. Berlinck and Antonio Ferreira-Pereira
Mar. Drugs 2024, 22(11), 502; https://doi.org/10.3390/md22110502 - 5 Nov 2024
Viewed by 548
Abstract
Numerous Candida species are responsible for fungal infections; however, Candida albicans stands out among the others. Treatment with fluconazole is often ineffective due to the resistance phenotype mediated by transmembrane transporters and/or biofilm formation, mechanisms of resistance commonly found in C. albicans strains. [...] Read more.
Numerous Candida species are responsible for fungal infections; however, Candida albicans stands out among the others. Treatment with fluconazole is often ineffective due to the resistance phenotype mediated by transmembrane transporters and/or biofilm formation, mechanisms of resistance commonly found in C. albicans strains. A previous study by our group demonstrated that batzelladine D can inhibit the Pdr5p transporter in Saccharomyces cerevisiae. In the present study, our aim was to investigate the efficacy of batzelladine D in inhibiting the main efflux pumps of Candida albicans, CaCdr1p and CaCdr2p, as well as to evaluate the effect of the compound on C. albicans biofilm. Assays were conducted using a clinical isolate of Candida albicans expressing both transporters. Additionally, to allow the study of each transporter, S. cerevisiae mutant strains overexpressing CaCdr1p or CaCdr2p were used. Batzelladine D was able to reverse the fluconazole resistance phenotype by acting on both transporters. The compound synergistically improved the effect of fluconazole against the clinical isolate when tested in the Caenorhabditis elegans animal model. Moreover, the compound disrupted the preformed biofilm. Based on the obtained data, the continuation of batzelladine D studies as a potential new antifungal agent and/or chemosensitizer in Candida albicans infections can be suggested. Full article
(This article belongs to the Special Issue Marine Anti-Biofilm Compounds from Natural to Synthetic Compounds)
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Graphical abstract

Graphical abstract
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<p>Effect of batzelladine D on the growth of 95-142, AD/CaCDR1 and AD/CaCDR2 cells. Yeast strains were incubated in the presence of two-fold serial dilutions (50–0.39 µM) of batzelladine D at 30 or 37 °C for 48 h. * Significantly lower than the untreated control (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Chemosensitization of fluconazole-resistant strains by batzelladine D. Five-fold serial dilutions were spotted on YPD or Sabouraud agar in the presence or absence of subinhibitory fluconazole concentrations specific for each strain. Batzelladine D was also added to the medium at final concentrations of 5 and 10 µM. Positive chemoreversing control was conducted with FK506 at 10 µM. Negative chemoreversing controls were performed using agar medium without supplementation and DMSO 0.5%. * FK506 is not an effective inhibitor of the CaCdr2p; thus, it was not employed as a positive control for reversal on the AD/CaCDR2 strain.</p>
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<p>(<b>A</b>) Left: original and redocking superposition of FK506 inhibitor within the CaCdr1 protein; Right: a closer view of the superposition; (<b>B</b>) Left: Original and redocking pose superposition of milbemycin within CaCdr2 protein; Right: a closer view of the superposition.</p>
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<p>(<b>A</b>) batzelladine D-FK506 superposition into active site of CaCdr1 protein and molecular interactions diagram for FK506 and batzelladine D. (<b>B</b>) batzelladine D-milbemycin A4 superposition into active site of CaCdr2 protein and molecular interactions diagrams for both molecules.</p>
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<p>Effect of batzelladine D on <span class="html-italic">C. albicans</span> 95-142 biofilm formation. Yeast strains were incubated in the presence of two-fold serial dilutions (50–3.125 µM) of batzelladine D at 37 °C for 48 h. The values of the untreated control were set to 100%. * Significantly lower than the untreated control (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Effect of batzelladine D on <span class="html-italic">C. albicans</span> 95-142 preformed biofilm. (<b>A</b>) Mature biofilms were incubated at 37 °C for 24 h in the presence of two-fold serial dilutions (50–3.125 µM) of batzelladine D. The values of the untreated control were set to 100%. * Significantly lower than the untreated control (<span class="html-italic">p</span> &lt; 0.05). (<b>B</b>) Confocal microscopy images of the mature biofilm control (left) and mature biofilm treated with batzelladine D 50 µM (right).</p>
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<p>In vivo efficacy of batzelladine D and batzelladine D/fluconazole in <span class="html-italic">Caenorhabditis elegans</span> infected with <span class="html-italic">Candida albicans</span> 95-142. <span class="html-italic">C. elegans</span> worms were infected with <span class="html-italic">C. albicans</span> 95-142 and then treated with subinhibitory concentration of fluconazole (48 µg/mL); subinhibitory concentration of batzelladine D (3.125 µM); MIC value of batzelladine D (6.25 µM); effective concentration of batzelladine D against preformed biofilm (50 µM); and batzelladine D (3.125 µM) + fluconazole (48 µg/mL). Treatment with PBS (viability control), DMSO 0.5% (DMSO control), and MIC of fluconazole 128 µg/mL (FLC control) served as controls. * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Toxicity effect of batzelladine D against <span class="html-italic">C. elegans</span>. Nematodes were incubated in the presence of two-fold serial dilutions (50–3.125 µM) of batzelladine D at 26 °C for 72 h, and later classified as live and dead. The values of the untreated control were set to 100%. * Significantly lower than the untreated control (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Minimum energy structure for tacrolimus, milbemicyn and batzelladine D at wB97XD/6-31G++dp level of theory. (<b>A</b>) CaCdr1p with tacrolimus as inhibitor; (<b>B</b>) CaCdr2p with milbemycin as inhibitor; both, A and B represent the structures retrieved from PDB and unitpro, respectively.</p>
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33 pages, 6357 KiB  
Article
A Holistic Analysis on Risks of Post-Disaster Reconstruction Using RStudio Bibliometrix
by Merve Serter and Gulden Gumusburun Ayalp
Sustainability 2024, 16(21), 9463; https://doi.org/10.3390/su16219463 - 31 Oct 2024
Viewed by 596
Abstract
Post-disaster reconstruction (PDR) is a complex and unpredictable process, especially concerning the construction sector, where understanding associated risks is increasingly vital. This study investigates and evaluates the present condition of post-disaster reconstruction risk (RoPDR) and discerns research trends and deficiencies in the domain [...] Read more.
Post-disaster reconstruction (PDR) is a complex and unpredictable process, especially concerning the construction sector, where understanding associated risks is increasingly vital. This study investigates and evaluates the present condition of post-disaster reconstruction risk (RoPDR) and discerns research trends and deficiencies in the domain via a systematic literature review (SLR) and bibliometric analysis. The Web of Science (WoS) was preferred for its extensive repository of pivotal research publications and its integrated analytical capabilities for producing representative data. This study performed a comprehensive bibliometric analysis of 204 peer-reviewed journal articles regarding the risks associated with post-disaster reconstruction from 1993 to 2024, utilizing the R statistical programming package RStudio Bibliometrix R version 4.3.1 to map the research landscape, identify literature gaps, and analyze rising trends. As a result of the analyses, the risks of post-disaster reconstruction were classified into four main clusters. Despite numerous studies exploring post-disaster reconstruction through diverse perspectives and methodologies, the associated risks of these projects remain inadequately analyzed. This inaugural bibliometric study in the realm of RoPDR utilizes novel techniques, such as the h-index, thematic mapping, and trend topic analysis, to attain a comprehensive understanding. Hence, the outcome of this study will aid scholars and practitioners in thoroughly comprehending the present condition and identifying prospective research directions. Full article
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<p>Framework of methodology.</p>
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<p>Data gathering process.</p>
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<p>Distribution of RoPDR publication citations.</p>
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<p>Total number of articles, SCP, and MCP by the most active 20 countries.</p>
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<p>The top 10 most relevant and influential sources publishing RoPDR papers.</p>
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<p>Productivity patterns of the top 10 researchers in the RoPDR domain over time.</p>
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<p>Frequently used words in the field of RoPDRs.</p>
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<p>Keyword network analysis.</p>
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<p>Word cloud analysis of RoPDRs.</p>
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<p>Total frequency based on keywords.</p>
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<p>Thematic mapping.</p>
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<p>(<b>a</b>) Cluster analysis k = 5; (<b>b</b>) cluster analysis k = 4.</p>
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<p>Thematic evaluation of research on RoPDR (1993–2024) using Sankey diagrams.</p>
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<p>Trend topics in RoPDRs.</p>
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24 pages, 6486 KiB  
Article
Unexpected Course of Reaction Between (1E,3E)-1,4-Dinitro-1,3-butadiene and N-Methyl Azomethine Ylide—A Comprehensive Experimental and Quantum-Chemical Study
by Mikołaj Sadowski and Karolina Kula
Molecules 2024, 29(21), 5066; https://doi.org/10.3390/molecules29215066 - 26 Oct 2024
Viewed by 627
Abstract
In recent times, interest in the chemistry of conjugated nitrodienes is still significantly increasing. In particular, the application of these compounds as building blocks to obtain heterocycles is a popular object of research. Therefore, in continuation of our research devoted to the topic [...] Read more.
In recent times, interest in the chemistry of conjugated nitrodienes is still significantly increasing. In particular, the application of these compounds as building blocks to obtain heterocycles is a popular object of research. Therefore, in continuation of our research devoted to the topic of conjugated nitrodienes, experimental and quantum-chemical studies of a cycloaddition reaction between (1E,3E)-1,4-dinitro-1,3-butadiene and N-methyl azomethine ylide have been investigated. The computational results present that the tested reaction is realized through a pdr-type polar mechanism. In turn, the experimental study shows that in a course of this cycloaddition, only one reaction product in the form of 1-methyl-3-(trans-2-nitrovinyl)-Δ3-pyrroline is created. The constitution of this compound has been confirmed via spectroscopic methods. Finally, ADME analysis indicated that the synthesized Δ3-pyrroline exhibits biological potential, and it is a good drug candidate according to Lipinski, Veber and Egan rules. Nevertheless, PASS simulation showed that the compound exhibits weak antimicrobial, inhibitory and antagonist properties. Preliminary in silico research shows that although the obtained Δ3-pyrroline is not a good candidate for a drug, the presence of a nitrovinyl moiety in its structure indicates that the compound is an initial basis for further modifications. Full article
(This article belongs to the Special Issue Heterocyclic Compounds: Synthesis, Application and Theoretical Study)
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<p>Examples of the application of CNDs in organic synthesis.</p>
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<p>B3LYP/6-31G(d) ELF attractor positions of the core and valence basins for nitrodiene (<b>1</b>) and ylide (<b>2</b>) together with the most significant ELF valence basin populations. The ELF attractors are shown as pink spheres. The electron populations are given as the average number of electrons [e].</p>
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<p>B3LYP/6-31G(d) ELF localization domains for nitrodiene (<b>1</b>) and ylide (<b>2</b>) represented at an isosurface value of ELF = 0.75. For ELF localization domains, protonated basins are shown in blue, monosynaptic basins in red, disynaptic basins in green and core basins in magenta.</p>
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<p>B3LYP/6-31G(d) proposed ELF-based Lewis-like structures with the natural atomic charges for nitrodiene (<b>1</b>) and ylide (<b>2</b>) as well as the molecular electrostatic potential maps. Negative charges are coloured in red, while negligible charges are coloured in green. Natural atomic charges are given as the average number of electrons [e].</p>
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<p>B3LYP/6-31G(d) HOMO–LUMO energy gap ΔE diagram for nitrodiene (<b>1</b>) and ylide (<b>2</b>).</p>
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<p>B3LYP/6-31G(d) visualization of the flux of the electron density between nitrodiene (<b>1</b>) and ylide (<b>2</b>) together with the driving force of the process Δω parameter.</p>
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<p>B3LYP/6-31G(d) local electronic properties for nitrodiene (<b>1</b>) and ylide (<b>2</b>) presented as three-dimensional (3D) representations of Mulliken atomic spin densities for radical anion of <b>1</b><sup>−</sup> and radical cation <b>2</b><sup>+</sup>, together with the electrophilic P<sub>k</sub><sup>+</sup> and the nucleophilic P<sub>k</sub><sup>−</sup> Parr functions values (given in yellow), as well as the indices of the local electrophilicity ω<sub>k</sub> of <b>1</b><sup>−</sup> (given in red, in eV) and the local nucleophilicity N<sub>k</sub> of <b>2</b><sup>+</sup> (given in blue, in eV).</p>
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<p>B3LYP/6-31G(d) global electrophilicity and global nucleophilicity indices, together with local electronic properties for pyrrolidine (<b>3</b>), presented as three-dimensional (3D) representations of Mulliken atomic spin densities for radical anion of <b>3<sup>−</sup></b> and electrophilic P<sub>k</sub><sup>+</sup> Parr functions values (given in yellow), as well as the indices of the local electrophilicity ω<sub>k</sub> of <b>3<sup>−</sup></b> (given in red, in eV).</p>
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<p>B3LYP/6-31G(d) ELF attractor positions of the valence basins with the most significant ELF valence basin populations and proposed ELF-based Lewis-like structures with the natural atomic charges for pyrrolidine (<b>3</b>). The ELF attractors are shown as pink spheres, while negative charges in Lewis-like structures are coloured in red. The electron populations as well as natural atomic charges are given as the average number of electrons [e].</p>
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<p>B3LYP/6-31G(d) HOMO–LUMO energy gap ΔE diagram for pyrrolidine (<b>3</b>).</p>
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<p>B3LYP/6-31G(d) HOMO–LUMO energy gap ΔE diagram together with values of the relative global minimums, given in frame, for theoretical possible conformers of Δ<sup>3</sup>-pyrroline (<b>3a</b>).</p>
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<p>B3LYP/6-31G(d) computed structure of s-<span class="html-italic">trans</span>-1′-<span class="html-italic">trans</span> conformer of pyrrolidine (<b>3</b>).</p>
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<p>The bioavailability radar for 1-methyl-3-(<span class="html-italic">trans</span>-2-nitrovinyl)-Δ<sup>3</sup>-pyrroline (<b>3a</b>). The pink area represents the optimal range for each property, including lipophilicity, size, polarity, insolubility, insaturation and flexibility.</p>
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<p>Theoretically possible reaction paths of 32CA between nitrodiene (<b>1</b>) and ylide (<b>2</b>).</p>
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<p>Method of the three-step synthesis of (1<span class="html-italic">E</span>,3<span class="html-italic">E</span>)-1,4-dinitro-1,3-butadiene (<b>1</b>).</p>
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<p><span class="html-italic">In situ</span> synthesis method of N-methyl azomethine ylide (<b>2</b>).</p>
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<p>Theoretically possible reaction paths of 32CA between nitrodiene (<b>1</b>) and ylide (<b>2</b>), including the potential HNO<sub>2</sub> elimination from the formed cycloadducts (<b>3</b>) and (<b>4</b>).</p>
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22 pages, 3309 KiB  
Article
Cross-Layer Routing Protocol Based on Channel Quality for Underwater Acoustic Communication Networks
by Jinghua He, Jie Tian, Zhanqing Pu, Wei Wang and Haining Huang
Appl. Sci. 2024, 14(21), 9778; https://doi.org/10.3390/app14219778 - 25 Oct 2024
Viewed by 517
Abstract
Due to the physical characteristics of acoustic channels, the performance of underwater acoustic communication networks (UACNs) is more susceptible to the impacts of multipath and Doppler effects. Channel quality can serve as a measure of the reliability of underwater communication links. A cross-layer [...] Read more.
Due to the physical characteristics of acoustic channels, the performance of underwater acoustic communication networks (UACNs) is more susceptible to the impacts of multipath and Doppler effects. Channel quality can serve as a measure of the reliability of underwater communication links. A cross-layer routing protocol based on channel quality (CLCQ) is proposed to improve the overall network performance and resource utilization. First, the BELLHOP ray model is used to calculate the channel impulse response combined with the winter sound speed profile data of a specific sea area. Then, the channel impulse response is integrated into the communication system to evaluate the channel quality between nodes based on the bit error rate (BER). Finally, during the selection of the next hop node, a reinforcement learning algorithm is employed to facilitate cross-layer interaction within the protocol stack. The optimal relay node is determined by the channel quality index (BER) from the physical layer, the buffer state from the data link layer, and the node residual energy. To enhance the algorithm’s convergence speed, a forwarding candidate set selection method is proposed which takes into account node depth, residual energy, and buffer state. Simulation results show that the packet delivery rate (PDR) of the CLCQ is significantly higher than that of Q-Learning-Based Energy-Efficient and Lifetime-Extended Adaptive Routing (QELAR) and Geographic and Opportunistic Routing (GEDAR). Full article
(This article belongs to the Special Issue Recent Advances in Underwater Acoustic Signal Processing)
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<p>The schematic diagram of the network.</p>
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<p>The sound speed profile.</p>
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<p>Example of channel (transmit depth 1000 m, receive depth 878.1 m, distance 536.8 m).</p>
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<p>OFDM underwater acoustic communication system implementation process.</p>
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<p>BER at different receiving depths and distances (transmitting depth 800 m).</p>
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<p>Protocol framework.</p>
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<p>Packet structure.</p>
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<p>V-value of the source node.</p>
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<p>Total energy consumption under different <math display="inline"><semantics> <mrow> <msub> <mi>φ</mi> <mrow> <mi>e</mi> <mi>n</mi> <mn>1</mn> </mrow> </msub> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <msub> <mi>φ</mi> <mrow> <mi>e</mi> <mi>n</mi> <mn>2</mn> </mrow> </msub> </mrow> </semantics></math> values.</p>
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<p>Residual energy variance under different <math display="inline"><semantics> <mrow> <msub> <mi>φ</mi> <mrow> <mi>e</mi> <mi>n</mi> <mn>1</mn> </mrow> </msub> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <msub> <mi>φ</mi> <mrow> <mi>e</mi> <mi>n</mi> <mn>2</mn> </mrow> </msub> </mrow> </semantics></math> values.</p>
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<p>Average end-to-end delay under different <math display="inline"><semantics> <mrow> <msub> <mi>φ</mi> <mi>t</mi> </msub> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <msub> <mi>α</mi> <mn>1</mn> </msub> </mrow> </semantics></math>, and <math display="inline"><semantics> <mrow> <msub> <mi>α</mi> <mn>2</mn> </msub> </mrow> </semantics></math> values.</p>
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<p>PDR under different <math display="inline"><semantics> <mrow> <msub> <mi>φ</mi> <mi>q</mi> </msub> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <msub> <mi>φ</mi> <mi>t</mi> </msub> </mrow> </semantics></math> values.</p>
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<p>Total energy consumption of different protocols.</p>
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<p>Residual energy variance of different protocols.</p>
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<p>Average end-to-end delay of different protocols.</p>
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<p>PDR of different protocols.</p>
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35 pages, 2192 KiB  
Systematic Review
Advanced Digital Technologies in the Post-Disaster Reconstruction Process—A Review Leveraging Small Language Models
by Alok Rawat, Emlyn Witt, Mohamad Roumyeh and Irene Lill
Buildings 2024, 14(11), 3367; https://doi.org/10.3390/buildings14113367 - 24 Oct 2024
Viewed by 1038
Abstract
Post-disaster reconstruction of the built environment represents a key global challenge that looks set to remain for the foreseeable future, but it also offers significant implications for the future sustainability and resilience of the built environment. The purpose of this research is to [...] Read more.
Post-disaster reconstruction of the built environment represents a key global challenge that looks set to remain for the foreseeable future, but it also offers significant implications for the future sustainability and resilience of the built environment. The purpose of this research is to explore the current applications of advanced digital/Industry 4.0 technologies in the post-disaster reconstruction (PDR) process with a view to improving its effectiveness and efficiency and the sustainability and resilience of the built environment. The extant research literature from the Scopus database on built environment reconstruction is identified and described. In a novel literature review approach, small language models are used for the classification and filtering of technology-related articles. A qualitative content analysis is then carried out to understand the extent to which Industry 4.0 technologies are applied in current reconstruction practice, mapping their applications to specific phases of the PDR process and identifying dominant technologies and key trends in technology deployment. The study reveals a rapidly evolving landscape of technological innovation with transformative potential in enhancing the efficiency, effectiveness, and sustainability of rebuilding efforts, with dominant technologies including GIS, remote sensing, AI, and BIM. Key trends include increasing automation and data-driven decision-making, integration of multiple Industry 4.0/digital technologies, and a growing emphasis on incorporating community needs and local knowledge into reconstruction plans. The study highlights the need for future research to address key challenges, such as developing interoperable platforms, addressing the ethical implications of using AI and big data, and exploring the contribution of Industry 4.0/digital technologies to sustainable reconstruction practices. Full article
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<p>Literature search and filtering flow chart. Ollama [<a href="#B24-buildings-14-03367" class="html-bibr">24</a>] and Langchain [<a href="#B25-buildings-14-03367" class="html-bibr">25</a>].</p>
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<p>Overall trend analysis with papers focused on technology applications.</p>
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<p>Application of individual Industry 4.0 technologies in the PDR research.</p>
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<p>Heatmap of technologies vs. different phases.</p>
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<p>Summary mapping diagram of Industry 4.0 Technologies to PDR phases.</p>
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8 pages, 220 KiB  
Article
Prevalence of Diabetic Retinopathy Among Diabetic Patients from Northeastern Bulgaria
by Zornitsa Zlatarova, Elitsa Hristova, Kristina Bliznakova, Virginia Atanasova, Zhaneta Yaneva, Darina Koseva, Lidiya Zaduryan, Gabriela Vasileva, Daliya Stefanova and Klara Dokova
Diagnostics 2024, 14(20), 2340; https://doi.org/10.3390/diagnostics14202340 - 21 Oct 2024
Viewed by 551
Abstract
Background: Diabetic retinopathy (DR) is a leading cause of visual impairment globally among working-aged individuals. This study aims to update data on DR prevalence in Bulgaria. Methods: The present cross-sectional study was conducted between 1 January 2022 and 1 January 2023, using a [...] Read more.
Background: Diabetic retinopathy (DR) is a leading cause of visual impairment globally among working-aged individuals. This study aims to update data on DR prevalence in Bulgaria. Methods: The present cross-sectional study was conducted between 1 January 2022 and 1 January 2023, using a local diabetes registry from the city of Varna as a sampling framework. In total, 587 diabetic patients underwent DR examination. Data included demographics, diabetes type/duration, treatment, and ophthalmic history. DR status was assessed using indirect slit-lamp biomicroscopy or digital fundus photography, graded by the International Clinical Diabetic Retinopathy Scale. Results: Of 587 participants, 13 were excluded due to cataract-related ungradable images. The median age was 65 years (IQR 56–73), with a slight female predominance (54%). The overall prevalence of any DR was 39.9% (95% CI 35.9–44.0), with non-proliferative DR (NPDR) at 27.5%, proliferative DR (PDR) at 7.3%, and macular edema (DME) at 5%. Type 1 diabetes patients had significantly higher DR prevalence (68.8%) than type 2 (34.1%, p < 0.001). Men exhibited higher DR prevalence. Age and diabetes duration correlated positively with DR prevalence. Insulin treatment was associated with higher DR prevalence (55.6%) than oral antidiabetic treatment (22.5%, p < 0.001) for type 2 diabetes patients. Among those diagnosed with DR, 70.9% received treatment, mainly laser therapy. Conclusions: These findings provide epidemiological insights for future research and emphasize the need for a comprehensive national DR screening program in Bulgaria. Technological advancements enable proactive measures to mitigate DR-related visual impairment and blindness, including widespread screening, even in rural areas. Full article
(This article belongs to the Special Issue Updates on the Diagnosis and Management of Retinal Diseases)
15 pages, 2823 KiB  
Article
Proliferative Diabetic Retinopathy Microenvironment Drives Microglial Polarization and Promotes Angiogenesis and Fibrosis via Cyclooxygenase-2/Prostaglandin E2 Signaling
by Shuta Kishishita, Ayumi Usui-Ouchi, Yasuo Ouchi, Yuiko Hata, Nobuyuki Ebihara and Shintaro Nakao
Int. J. Mol. Sci. 2024, 25(20), 11307; https://doi.org/10.3390/ijms252011307 - 21 Oct 2024
Viewed by 669
Abstract
Diabetic retinopathy (DR) is the leading cause of visual impairment, particularly in the proliferative form (proliferative DR [PDR]). The impact of the PDR microenvironment on microglia, which are the resident immune cells in the central nervous system, and the specific pathological changes it [...] Read more.
Diabetic retinopathy (DR) is the leading cause of visual impairment, particularly in the proliferative form (proliferative DR [PDR]). The impact of the PDR microenvironment on microglia, which are the resident immune cells in the central nervous system, and the specific pathological changes it may induce remain unclear. This study aimed to investigate the role of microglia in the progression of PDR under hypoxic and inflammatory conditions. We performed a comprehensive gene expression analysis using human-induced pluripotent stem cell-derived microglia under different stimuli (dimethyloxalylglycine (DMOG), lipopolysaccharide (LPS), and DMOG + LPS) to mimic the hypoxic inflammatory environment characteristic of PDR. Principal component analysis revealed distinct gene expression profiles, with 76 genes synergistically upregulated under combined stimulation. Notably, prostaglandin-endoperoxide synthase 2 (encoding cyclooxygenase (COX)-2) exhibited the most pronounced increase, leading to elevated prostaglandin E2 (PGE2) levels and driving pathological angiogenesis and inflammation via the COX-2/PGE2/PGE receptor 2 signaling axis. Additionally, the upregulation of the fibrogenic genes snail family transcriptional repressor 1 and collagen type I alpha 1 chain suggested a role for microglia in fibrosis. These findings underscore the critical involvement of microglia in PDR and suggest that targeting both the angiogenic and fibrotic pathways may present new therapeutic strategies for managing this condition. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Therapeutics in Retinopathy)
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<p>Distinct global gene expression profiles in induced pluripotent stem cell-derived microglia (iMGs) under hypoxia and immune activation. Comprehensive gene expression profiles were analyzed to assess the effects of hypoxia and innate immune activation on human iMGs using lipopolysaccharide (LPS) and dimethyloxaloylglycine (DMOG) (<b>A</b>). The heatmap shows that DMOG stimulation resulted in the significant upregulation of 216 genes, whereas LPS stimulation upregulated 912 genes compared with the control. In addition, these differences were confirmed, highlighting a subset of genes that was synergistically upregulated by both stimuli (<b>B</b>). Pathway analysis of the differentially expressed genes indicated the activation of the vascular endothelial growth factor and hypoxia-inducible factor-1 signaling pathways under DMOG stimulation, indicating a hypoxic response (<b>C</b>). Conversely, LPS stimulation enhanced Toll-like receptor signaling, nuclear factor-kappaB signaling, and tumor necrosis factor signaling, suggesting heightened immune activation (<b>D</b>).</p>
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<p>Synergistic upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2) and pathological gene networks in induced pluripotent stem cell-derived microglia under hypoxia and immune activation. We found 76 genes that were significantly and synergistically upregulated by both innate immune-activating stimulation by lipopolysaccharide and hypoxic stimulation by dimethyloxaloylglycine compared with either stimulus alone (false discovery rate &lt; 0.1, fold change &gt; 1.5) (<b>A</b>). The top 20 synergistically upregulated genes are highlighted; the most significantly upregulated gene is PTGS2, which encodes cyclooxygenase 2 (<b>B</b>). Gene ontology analysis of the synergistically upregulated genes identified significant terms related to angiogenesis, cell migration, chemotaxis, and fibrosis (<b>C</b>).</p>
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<p>Synergistic upregulation of cyclooxygenase 2 and prostaglandin E2 in response to hypoxia and inflammation. Quantitative polymerase chain reaction for prostaglandin-endoperoxide synthase 2 (PTGS2) and enzyme-linked immunosorbent assay (ELISA) for prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) were performed under 200 μM dimethyloxaloylglycine (DMOG), 100 ng/mL lipopolysaccharide (LPS), or combined DMOG and LPS stimulation for 24 h. The expression of PTGS2 mRNA was significantly upregulated, showing a 10–20-fold increase with single LPS or DMOG stimulation and a 150–200-fold increase with combined DMOG and LPS stimulation compared with the control (<b>A</b>). ELISA measurements indicated increased levels of PGE2, but not PGF2α, in the culture supernatant under these conditions (<b>B</b>,<b>C</b>). Aqueous humor samples were collected from five patients with proliferative diabetic retinopathy (PDR) accompanied with diabetic macular edema (two males and three females; average age, 64.4 ± 6.2 years) and five age-matched patients without any retinal diseases as control (two males and three females; average age, 64.0 ± 10.1 years) for ELISA assay. Vitreous humor samples were also collected from five patients with PDR (four males and one female; average age, 57.6 ± 5.9 years) and five age-matched patients without any retinal diseases as control (three males and two females; average age, 61.0 ± 5.2 years). PGE2 concentrations were significantly elevated in the aqueous and vitreous humors of patients with PDR compared with those in the controls (<b>D</b>,<b>E</b>). * <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.</p>
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<p>Synergistic activation of angiogenesis- and fibrosis-related genes in induced pluripotent stem cell-derived microglia under hypoxia and inflammation. Quantitative polymerase chain reaction for genes associated with angiogenesis and fibrovascular proliferation in proliferative diabetic retinopathy (PDR) were performed under 200 μM dimethyloxaloylglycine (DMOG), 100 ng/mL lipopolysaccharide (LPS), or combined DMOG and LPS stimulation for 24 h. The expression levels of vascular endothelial growth factor A, matrix metalloproteinase 2, and interleukin-6, key contributors to pathological neovascularization in PDR, were significantly upregulated under combined DMOG and LPS stimulation compared with monostimulation (<b>A</b>–<b>C</b>). Snail family transcriptional repressor 1 (SNAI1), a master transcription factor that regulates mesenchymal transition, was upregulated under both DMOG and LPS stimulation (<b>D</b>). Collagen type I alpha 1 chain, a major extracellular matrix component induced by SNAI1 activation, markedly increased under combined stimulation (<b>E</b>). ** <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.</p>
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<p>Celecoxib inhibits cyclooxygenase 2 (COX-2) mediated inflammatory, angiogenic, and fibrotic gene expression in induced pluripotent stem cell-derived microglia (iMGs) under hypoxia and inflammation. We treated iMGs stimulated by 200 μM dimethyloxaloylglycine (DMOG) and 100 ng/mL lipopolysaccharide (LPS) with 10 μM celecoxib, the selective COX-2 inhibitor, for 24 h. Celecoxib treatment significantly downregulated prostaglandin E2 production in the culture supernatant (<b>A</b>). The quantitative polymerase chain reaction results showed that celecoxib markedly reduced the expression of interleukin-6 (IL-6) in both DMOG and LPS-stimulated iMGs (<b>B</b>). Celecoxib significantly decreased the expression of vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase 2, the critical drivers of pathological neovascularization, which were notably upregulated under combined DMOG and LPS stimulation (<b>C</b>). The expression of snail family transcriptional repressor 1, a key transcription factor for fibrosis, and its downstream target, collagen type I alpha 1 chain, was significantly reduced by celecoxib treatment (<b>D</b>). The expression of VEGFA and IL-6, which was elevated by DMOG + LPS, was suppressed in a dose-dependent manner by celecoxib (<b>E</b>). * <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.</p>
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<p>The cyclooxygenase 2/prostaglandin E2/PGE receptor 2 (EP2) axis as a central driver of angiogenesis and inflammation in induced pluripotent stem cell-derived microglia (iMGs), with distinct pathways governing fibrosis. The genes encoding prostaglandin receptors EP2 (PTGER2) and EP4 (PTGER4) were expressed in human iMGs and were notably upregulated by 200 μM dimethyloxaloylglycine (DMOG) and 100 ng/mL lipopolysaccharide (LPS) stimulation for 24 h, whereas the genes encoding EP1 (PTGER1) and EP3 (PTGER3) were not expressed (<b>A</b>). To pinpoint which prostaglandin receptors drive the upregulation of angiogenic and fibrogenic genes, we treated iMGs with specific antagonists PF04418948, targeting EP2, and GW627368, targeting EP4 receptors, under combined 200 μM DMOG and 100 ng/mL LPS stimulation for 24 h. Treatment of iMGs with PF04418948 significantly downregulated vascular endothelial growth factor A and interleukin-6 mRNA expression, underscoring the pivotal role of the EP2 receptor in mediating these pathways (<b>B</b>). However, SNAI1 and COL1A1 did not respond to EP2 or EP4 antagonists, indicating that they have different regulatory mechanisms (<b>C</b>). * <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.</p>
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8 pages, 400 KiB  
Communication
The Co-Design of a Locally Led Health Professional Education Curriculum in Lao People’s Democratic Republic
by Amy Gray, Sysavanh Phommachanh, Niranh Phoumindr and Mayfong Mayxay
Int. Med. Educ. 2024, 3(4), 426-433; https://doi.org/10.3390/ime3040032 - 17 Oct 2024
Viewed by 574
Abstract
(1) Background: There is a need to scale and transform health professional education (HPE) globally to not only improve the quantity but also the quality of health workers. This paper describes the approach undertaken by a Health University in Lao PDR. (2) Approach: [...] Read more.
(1) Background: There is a need to scale and transform health professional education (HPE) globally to not only improve the quantity but also the quality of health workers. This paper describes the approach undertaken by a Health University in Lao PDR. (2) Approach: The HPE curriculum was designed in an iterative process with key stakeholders from both the institution and government, with external expert advice. (3) Outcomes: The curriculum was successfully developed consisting of nine core modules and one elective module, reflecting both elements seen globally in HPE curricula as well as reflecting local needs. The content and teaching methods were validated and reviewed through piloting with local education leaders. (4) Conclusions: Despite the need to scale HPE globally, there are few examples of how this can be achieved in countries in which large gaps exist in HPE capacity. This paper provides one such example, through recognizing that sustained external partnerships will still be needed for successful future implementation. Full article
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<p>Responses on a 4-point Likert scale to surveys of piloted content including (a) its educational value, (b) engagement and interactivity, (c) whether it will change their practice, and (d) whether they feel able to teach the content. The numbers on the <span class="html-italic">y</span>-axis represent the percentage of responses in each category.</p>
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16 pages, 3319 KiB  
Article
Performance of Micropiled-Raft Foundations in Sand
by Adel Hanna and Farhad Nabizadeh
Geotechnics 2024, 4(4), 1065-1080; https://doi.org/10.3390/geotechnics4040054 - 15 Oct 2024
Viewed by 379
Abstract
Micropiles were first used to repair the damaged structures of “Scuola Angiulli” in Naples after World War II. They are known as small versions of regular piles, with a diameter of less than 30 cm, and are made of high-strength, steel casing and/or [...] Read more.
Micropiles were first used to repair the damaged structures of “Scuola Angiulli” in Naples after World War II. They are known as small versions of regular piles, with a diameter of less than 30 cm, and are made of high-strength, steel casing and/or threaded bars, produce minimal noise and vibration during installation, and use lightweight machinery. They are capable to withstand axial loads and moderate lateral loads. They are used for underpinning existing foundations and to restore historical buildings and to support moderate structures. In the literature, several reports can be found dealing with micropiles, yet little has been reported on Micropiled-Raft Foundations (MPR). This technology did not receive the recognition it deserved until the 1970s when its technical and economic benefits were noted. A series of laboratory tests and numerical modeling were developed to examine the parameters governing the performance of MPR, including the relative density of the sand, the micropile spacing, and the rigidity of the raft. The numerical model, after being validated with the present experimental results, was used to generate data for a wide range of governing parameters. The theory developed by Poulos (2001) (PDR) to predict the capacity of pile-raft foundations was adopted for the design of MPR. The PDR method is widely used by geotechnical engineers because of its simplicity. Full article
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<p>Schematic diagram of the test setup.</p>
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<p>Test in progress of four micropiled-raft system.</p>
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<p>Instrumentations installed on the experimental models. (<b>a</b>) Unpiled rafts. (<b>b</b>) One-micropiled raft. (<b>c</b>) Four-micropiled-raft system.</p>
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<p>Test results: load–settlement curve for unpiled-raft (D<sub>r</sub> = 45%).</p>
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<p>Test results: load–settlement curve for single pile (D<sub>r</sub> = 60%).</p>
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<p>Test results: load–settlement curve for single-pile raft. (<b>a</b>) D<sub>r</sub> = 30%. (<b>b</b>) D<sub>r</sub> = 45%. (<b>c</b>) D<sub>r</sub> = 60%.</p>
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<p>Test results: load–settlement curve for 4-micropiled raft. (<b>a</b>) (s/d = 3, D<sub>r</sub> = 30%). (<b>b</b>) (s/d = 3, D<sub>r</sub> = 45%).</p>
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<p>Test results: load–settlement curves for unpiled raft, single micropile, and MPR for s/d = 3.</p>
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<p>Comparison between experimental and numerical test results (unpiled raft 13 × 13 cm)—D<sub>r</sub> = 60%.</p>
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<p>Load versus pile spacing for MPR with rigid and semi-flexible raft.</p>
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<p>Load sharing for micropiles and raft: (<b>a</b>) s/d = 3, D<sub>r</sub> = 30%; (<b>b</b>) s/d = 3 D<sub>r</sub> = 45%.</p>
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<p>Ratio of the actual to anticipated stiffness of the MPRs.</p>
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13 pages, 1528 KiB  
Article
Experimental Performance Comparison of Proactive Routing Protocols in Wireless Mesh Network Using Raspberry Pi 4
by Dana Turlykozhayeva, Symbat Temesheva, Nurzhan Ussipov, Aslan Bolysbay, Almat Akhmetali, Sayat Akhtanov and Xiao Tang
Telecom 2024, 5(4), 1008-1020; https://doi.org/10.3390/telecom5040051 - 10 Oct 2024
Viewed by 935
Abstract
Nowadays, Wireless Mesh Networks (WMNs) are widely deployed in communication areas due to their ease of implementation, dynamic self-organization, and cost-effectiveness. The design of routing protocols is critical for ensuring the performance and reliability of WMNs. Although there have been numerous experimental works [...] Read more.
Nowadays, Wireless Mesh Networks (WMNs) are widely deployed in communication areas due to their ease of implementation, dynamic self-organization, and cost-effectiveness. The design of routing protocols is critical for ensuring the performance and reliability of WMNs. Although there have been numerous experimental works on WMNs in the past decade, only a few of them have been tested in real-world scenarios. This article presents a comparative analysis of three proactive routing protocols, OLSR, BATMAN, and Babel, using Raspberry Pi 4 devices. The evaluation, conducted at Al-Farabi Kazakh National University, covers both indoor and outdoor scenarios, focusing on key metrics such as bandwidth, Packet Delivery Ratio (PDR), and jitter. In outdoor scenarios, OLSR achieved the highest bandwidth at 2.9 Mbps, while BATMAN and Babel lagged. Indoor tests revealed that Babel initially outperformed with the highest bandwidth of 57.19 Mb/s but suffered from scalability issues, while BATMAN and OLSR exhibited significant declines in performance as network size increased. For PDR, BATMAN performed best with a decline from 100% to 42.8%, followed by OLSR with a moderate drop, and Babel with the greatest decrease. For jitter, OLSR showed the most stable performance, increasing from 0.281 ms to 2.58 ms at eleven nodes, BATMAN exhibited moderate increases, and Babel experienced the highest rise. Full article
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<p>WMN architecture.</p>
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<p>Sorting of WMN routing protocols.</p>
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<p>Raspberry Pi 4 Model B node (<b>a</b>) internal appearance and (<b>b</b>) external appearance.</p>
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<p>An indoor WMN testbed featuring orange nodes as endpoints and blue nodes as routers.</p>
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<p>Outdoor WMN testbed.</p>
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<p>Bandwidth (outdoor testbed).</p>
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<p>Bandwidth (indoor testbed).</p>
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<p>Packet Delivery Ratio.</p>
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<p>Jitter of 3 routing protocols.</p>
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16 pages, 2436 KiB  
Article
Cardiovascular Risk Factors as Independent Predictors of Diabetic Retinopathy in Type II Diabetes Mellitus: The Development of a Predictive Model
by Cristian Dan Roşu, Melania Lavinia Bratu, Emil Robert Stoicescu, Roxana Iacob, Ovidiu Alin Hațegan, Laura Andreea Ghenciu and Sorin Lucian Bolintineanu
Medicina 2024, 60(10), 1617; https://doi.org/10.3390/medicina60101617 - 2 Oct 2024
Viewed by 1392
Abstract
Background: Diabetic retinopathy (DR) is a leading cause of blindness in patients with type 2 diabetes mellitus (T2DM). Cardiovascular risk factors, such as hypertension, obesity, and dyslipidemia, may play a crucial role in the development and progression of DR, though the evidence [...] Read more.
Background: Diabetic retinopathy (DR) is a leading cause of blindness in patients with type 2 diabetes mellitus (T2DM). Cardiovascular risk factors, such as hypertension, obesity, and dyslipidemia, may play a crucial role in the development and progression of DR, though the evidence remains mixed. This study aimed to assess cardiovascular risk factors as independent predictors of DR and to develop a predictive model for DR progression in T2DM patients. Methods: A retrospective cross-sectional study was conducted on 377 patients with T2DM who underwent a comprehensive eye exam. Clinical data, including blood pressure, lipid profile, BMI, and smoking status, were collected. DR staging was determined through fundus photography and classified as No DR, Non-Proliferative DR (NPDR), and Mild, Moderate, Severe, or Proliferative DR (PDR). A Multivariate Logistic Regression was used to evaluate the association between cardiovascular risk factors and DR presence. Several machine learning models, including Random Forest, XGBoost, and Support Vector Machines, were applied to assess the predictive value of cardiovascular risk factors and identify key predictors. Model performance was evaluated using accuracy, precision, recall, and ROC-AUC. Results: The prevalence of DR in the cohort was 41.6%, with 34.5% having NPDR and 7.1% having PDR. A multivariate analysis identified systolic blood pressure (SBP), LDL cholesterol, and body mass index (BMI) as independent predictors of DR progression (p < 0.05). The Random Forest model showed a moderate predictive ability, with an AUC of 0.62 for distinguishing between the presence and absence of DR XGBoost showing a better performance, featuring a ROC-AUC of 0.68, while SBP, HDL cholesterol, and BMI were consistently identified as the most important predictors across models. After tuning, the XGBoost model showed a notable improvement, with an ROC-AUC of 0.72. Conclusions: Cardiovascular risk factors, particularly BP and BMI, play a significant role in the progression of DR in patients with T2DM. The predictive models, especially XGBoost, showed moderate accuracy in identifying DR stages, suggesting that integrating these risk factors into clinical practice may improve early detection and intervention strategies for DR. Full article
(This article belongs to the Special Issue Cardiovascular Diseases and Type 2 Diabetes: 2nd Edition)
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<p>The boxplot visualizes LDL levels in individuals with and without diabetic retinopathy. The median LDL levels appear to be similar between both groups, and the distribution of LDL levels is also relatively similar. There are a few outliers in both groups, but, overall, there does not seem to be a significant difference in LDL levels between those with and without DR, which is consistent with the <span class="html-italic">t</span>-test results.</p>
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<p>Trend in mean blood pressure across DR stages. This line graph illustrates the relationship between mean SBP and DBP and the progression of DR. As DR progresses, there is a clear upward trend in both systolic (blue line) and diastolic (green line) blood pressure, with the highest values being observed in patients with PDR.</p>
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<p>The confusion matrix for the XGBoost model predicting the presence of diabetic retinopathy. The model demonstrates moderate performance in distinguishing between patients with No DR and those with any stage of DR.</p>
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<p>Feature importance in the XGBoost model for predicting diabetic retinopathy.</p>
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<p>The confusion matrix for the XGBoost model predicting diabetic retinopathy stages.</p>
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Article
Sequential Immune Acquisition of Monoclonal Antibodies Enhances Phagocytosis of Acinetobacter baumannii by Recognizing ATP Synthase
by Dong Huang, Zhujun Zeng, Zhuolin Li, Mengjun Li, Linlin Zhai, Yuhao Lin, Rui Xu, Jiuxin Qu, Bao Zhang, Wei Zhao and Chenguang Shen
Vaccines 2024, 12(10), 1120; https://doi.org/10.3390/vaccines12101120 - 29 Sep 2024
Viewed by 782
Abstract
Objectives: The aim of this study was to prepare monoclonal antibodies (mAbs) that broadly target Acinetobacter baumannii and protect against infection by multi-drug-resistant (MDR) A. baumannii from different sources. Methods: mAb 8E6 and mAb 1B5 were prepared by sequentially immunizing mice [...] Read more.
Objectives: The aim of this study was to prepare monoclonal antibodies (mAbs) that broadly target Acinetobacter baumannii and protect against infection by multi-drug-resistant (MDR) A. baumannii from different sources. Methods: mAb 8E6 and mAb 1B5 were prepared by sequentially immunizing mice with a sublethal inoculation of three heterogeneous serotypes of pan-drug-resistant (PDR) A. baumannii, ST-208, ST-195, and ST-229. Results: The cross-recognition of heterogeneous bacteria (n = 13) by two mAbs and potential targets was verified, and the in vitro antibacterial efficacy of mAbs was assessed. The median killing rate of mAb 8E6 against A. baumannii in the presence of complement and dHL-60 cells was found to be 61.51%, while that of mAb 1B5 was 41.96%. When only dHL-60 cells were present, the killing rate of mAb 8E6 was 65.73%, while that of mAb 1B5 was 69.93%. We found that mAb 8E6 and mAb 1B5 broadly targeted MDR A. baumannii on the ATP synthase complex and were equipped with an antibacterial killing ability by enhancing the innate immune bacteriolytic effect of ST-208 and ST-195 strains. Both monoclonal antibodies were validated to protect against respiratory infection at 4 and 24 h via enhancing the release of innate immune substances and inflammatory cytokines, effectively shortening the disease period in mice. Conclusions: mAb 8E6 and mAb 1B5 significantly enhanced the opsonization process of phagocytosis against A. baumannii strains prevalent in southern China by targeting ATP synthase antigens thereof, resulting in protective effects in mice. Full article
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<p>Each round of the sequential immunization strategy utilizes one of the three strains of PDR <span class="html-italic">A. baumannii</span>, eliciting strong cross-immune responses from sera that are generated through multiple rounds of immunization. The data are presented as the mean ± standard deviation (SD). A two-way ANOVA was conducted; *, <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. 0001 versus isotype mAb group. There was no statistically significant difference in the OD450 nm values among the three strains of <span class="html-italic">A. baumannii</span> when comparing the two distinct continuous detection gradients.</p>
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<p>(<b>A</b>) The mAbs-mediated complement and neutrophil bactericidal effects. The mAb 8E6-mediated complement susceptibility to SZ-Ab61 (ST-229) <span class="html-italic">A. baumannii</span> by guinea pig serum of 100 times dilution; the dose of antibody was 0.5–25 ng. (<b>B</b>) The bactericidal ability of SZ-Ab22 (ST-195) of the complement enhanced by mAb 8E6 (25 ng/well) also appeared in guinea pig serum diluted in 1:100. (<b>C</b>) Both mAbs showed bactericidal ability of the complement and dHL-60 cells against immune strains. Significant differences were detected using the one-way or two-way ANOVA test; *, <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; 0.0001; ns, not significant versus isotype mAb group. All tests were repeated three times.</p>
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<p>(<b>A</b>) The mAb 1B5- and mAb 8E6-mediated killing heterogenous ST-208 and ST-195 <span class="html-italic">A. baumannii</span> with specificity when combined with guinea pig complement and dHL-60 cells. Each well was consistently replicated in three wells within each experimental cohort; *, <span class="html-italic">p</span> &lt; 0.05 versus isotype mAb group by Tukey’s post hoc test. The complement was diluted 3000 times to achieve a non-specific killing rate (NSK) &lt; 25% in the PBS control. The NSK was calculated as NSK = [1 − (number of colonies in complement control group/number of colonies in inactivated complement control group)] × 100%. (<b>B</b>) The bactericidal rates of mAb 8E6 and mAb 1B5 against 13 strains of antibiotic-resistance <span class="html-italic">A. baumannii</span> were combined, and the median values were marked with “+”, no statistically significant differences (<span class="html-italic">p</span> &gt; 0.05) were observed in the rates of bacterial killing among mAb 8E6 and mAb 1B5.</p>
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<p>The mAbs enhancing the release of immune substances. (<b>A</b>) Mice were infected with ST-208 and ST-229 <span class="html-italic">A. baumannii</span> via nasal intubation drip, and then immediately injected into the mice (n = 10). All mice survived the study period. Significant differences were detected using the Tukey’s Honestly Significant Difference test; *, <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 versus isotype mAb group. All tests were repeated three times. (<b>B</b>) The microscopic architecture of the lungs in mice inoculated with PDR <span class="html-italic">A. baumannii</span> was scrutinized following mAbs protection. The lung tissue was separated at a specified time point and fixed with 4% paraformaldehyde. The rest of the lung tissue homogenates were 10-fold diluted and counted. The sections were stained with hematoxylin and eosin stain and observed under 100× and 400× magnification. More inflammatory cells were observed in the immunized mice during the early stages of the disease. The normal tissue structure recovered more quickly in the immunized mice than in the control group. Inflammatory cells are indicated by yellow pointers, while small focal infiltrations of lymphocytes are represented by blue pointers. Dot infiltrations of lymphocytes and granulocytes are denoted by red pointers, and compensatory increases in the surrounding alveoli are illustrated with gray pointers.</p>
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<p>Mice were inoculated with <span class="html-italic">A. baumannii</span> and subsequently treated with either an antibody or a control treatment (n = 5). Lung tissues were harvested at 4 and 24 h post-infection to assess bacterial load and cytokine levels. (<b>A</b>) No significant disparity in pulmonary bacterial burden was observed between the groups treated with the two distinct antibodies and the control group. (<b>B</b>) The cytokine levels in the lungs of mice administered mAbs exhibited significant variation when compared to the control group; *, <span class="html-italic">p</span> &lt; 0.05 compared to the isotype mAb or the PBS, as determined by the least significant difference (LSD) test.</p>
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<p>(<b>A</b>) Antibodies mediated cross-recognize heterogenous <span class="html-italic">A. baumannii</span> identification. The mAb 8E6 and mAb 1B5 specifically target <span class="html-italic">A. baumannii</span>, as determined using whole-cell ELISA, which was not observed in the isotype mAb; ****, <span class="html-italic">p</span> &lt; 0.0001, versus isotype mAb group by Dunnett’s <span class="html-italic">t</span>-test. (<b>B</b>) Western blot lanes 1, 3, and 5 represent bacterial lysate protein samples SZ-AB57, SZ-AB22, and SZ-AB61, respectively. Meanwhile, lanes 2, 4, and 6 were the lysates of these three bacteria treated with protease K separately. (<b>C</b>) The gray values obtained from the two methods were aggregated and analyzed using a paired <span class="html-italic">t</span>-test; *, <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>LC-MS/MS protein spectrometry results. X-axis represents <span class="html-italic">m</span>/<span class="html-italic">z</span> (mass-to-charge ratio); Y-axis represents relative abundance. The results of co-immunoprecipitation of mAb 1B5 with strain ZH-AB01 are shown in (<b>A</b>), the mAb 1B5 with strain SZ-AB57 are shown in (<b>B</b>); the co-immunoprecipitation of mAb 8E6 with strain ZH-AB01 are shown in (<b>C</b>), the mAb 8E6 with strain SZ-AB57 are shown in (<b>D</b>).</p>
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<p>3D structure of antibody–antigen combination forecast. The light purple color represents the position of the antigen subunit in the macromolecular ATP synthase. Green region is the antibody variable region structure simulated by the LYRA database, and the yellow region is the complementarity determining region identification combined with antigen epitope prediction. (<b>A</b>) The mAb 1B5 adheres to the subunit a. (<b>B</b>) mAb 8E6 adheres to the c ring.</p>
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