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44 pages, 13101 KB  
Review
Neural Melanocortin Receptors in Fish: Insights into Growth Regulation and Aquaculture Advancement
by Ren-Lei Ji and Ya-Xiong Tao
Biomolecules 2026, 16(6), 839; https://doi.org/10.3390/biom16060839 - 8 Jun 2026
Viewed by 409
Abstract
Understanding and regulating fish growth is vital for the economic sustainability of aquaculture. The melanocortin-3 and -4 receptors (MC3R/MC4R, known as neural MCRs), integral components of the leptin–melanocortin circuit, play crucial roles in vertebrate energy homeostasis and growth. Abnormal neural MCR signaling contributes [...] Read more.
Understanding and regulating fish growth is vital for the economic sustainability of aquaculture. The melanocortin-3 and -4 receptors (MC3R/MC4R, known as neural MCRs), integral components of the leptin–melanocortin circuit, play crucial roles in vertebrate energy homeostasis and growth. Abnormal neural MCR signaling contributes to human obesity. In teleosts, Mc4r was first comprehensively studied in goldfish in 2003. Since then, Mc4r has been characterized in various teleosts. Genetic and pharmacological reduction of neural Mcr signaling can increase feeding or growth in several fish models, although its aquaculture value must be evaluated using production endpoints such as feed conversion, body composition, reproduction, welfare, and biosafety. Furthermore, neural Mcrs also play a role in modulating reproductive processes and sexual function in teleosts. This review systematically examines recent progress on the roles of fish neural Mcrs, offering an overview of basic molecular characteristics, tissue distribution, and pharmacology. Physiological roles and mechanisms in growth regulation are reviewed. Finally, the potential and limitations of targeting neural Mcrs for aquaculture-relevant traits are discussed. This work contributes to our understanding of the evolution of energy homeostasis regulation in vertebrates, providing a foundation for healthier and more efficient aquaculture practices. Full article
(This article belongs to the Special Issue Vertebrate Comparative Genomics)
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41 pages, 12382 KB  
Review
A Review of Magnetically Controlled Continuum Robots: Principles, Classification, and Applications
by Mengyu Zhang, Liansheng Song, Wei Yu, Xindi An, Shuai Ren, Jiongzheng Zhang, Shuaida Wang, Jiefei Li, Junyang Li, Ying Li, Jianing Li and Pan Liao
Magnetochemistry 2026, 12(6), 66; https://doi.org/10.3390/magnetochemistry12060066 - 8 Jun 2026
Viewed by 202
Abstract
Magnetically controlled continuum robots (MCRs) emerge as a novel type of flexible robotic system that overcomes the physical limitations of traditional rigid-link structures, exhibiting high compliance, minimal invasiveness, and high spatial freedom. Through non-invasive, precise manipulation using magnetic fields, MCRs can achieve navigation [...] Read more.
Magnetically controlled continuum robots (MCRs) emerge as a novel type of flexible robotic system that overcomes the physical limitations of traditional rigid-link structures, exhibiting high compliance, minimal invasiveness, and high spatial freedom. Through non-invasive, precise manipulation using magnetic fields, MCRs can achieve navigation and positioning in complex and confined microenvironments such as blood vessels and cavities in the human body. Furthermore, MCRs have attracted increasing attention for minimally invasive intervention because they combine structural compliance with remote magnetic actuation. In this study, we first introduce the driving control of MCRs, including the driving principle and driving system. Next, we discuss different types of robots, such as guiding and steering robots, variable stiffness robots, multimodal motion robots, and bio-inspired continuum robots, as well as their fabrication materials and manufacturing processes. Subsequently, we analyze the achievements of these robots in the medical field, including cardiovascular treatment, cavity diagnosis and treatment, and bone and joint treatment. The review also discusses current challenges in control accuracy, biocompatibility, system integration, and clinical translation. Finally, we briefly summarize the research and discuss the current challenges and future development directions of MCRs. Full article
(This article belongs to the Special Issue Design and Application of Magnetic Microrobotics)
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9 pages, 770 KB  
Brief Report
Antimicrobial Resistance and Molecular Characteristics in Tigecycline-Resistant Escherichia coli Isolates from Broilers in Jinan City, China
by Rong Xi, Ban Li, Yunchen Zhou, Chengbo Wen, Yue Wu, Zhiyong Wu, Dexian Zhang and Jichang Li
Microorganisms 2026, 14(6), 1264; https://doi.org/10.3390/microorganisms14061264 - 4 Jun 2026
Viewed by 205
Abstract
The emergence of plasmid-mediated tigecycline resistance in food-producing animals poses a significant threat to global public health by compromising a last-resort antimicrobial. This study investigated the prevalence, antimicrobial susceptibility profiles, and molecular genetic characteristics of tigecycline-resistant Escherichia coli (E. coli) isolated [...] Read more.
The emergence of plasmid-mediated tigecycline resistance in food-producing animals poses a significant threat to global public health by compromising a last-resort antimicrobial. This study investigated the prevalence, antimicrobial susceptibility profiles, and molecular genetic characteristics of tigecycline-resistant Escherichia coli (E. coli) isolated from broiler cecal samples in the Jinan region of Shandong Province, China, between 2020 and 2024. Antimicrobial susceptibility testing showed that high-level resistance to colistin (87.5%, 14/16), florfenicol (81.3%, 13/15), and enrofloxacin (75.0%, 12/16) was observed. Notably, a single isolate was resistant to meropenem (6.3%, 1/16). Whole-genome sequencing and subsequent in silico analysis demonstrated that all 16 tigecycline-resistant isolates harbored the tigecycline resistance gene tet(X4), the primary determinant of resistance. Molecular typing identified a diverse population structure, with sequence type 224 (ST224) being the dominant clone, accounting for 37.5% (6/16) of the isolates. The genetic milieu of resistance was complex, characterized by the co-existence of tet(X4) with multiple other clinically important resistance genes, including the mobile colistin resistance gene mcr-1 (87.5%, 14/16) and various extended-spectrum β-lactamase genes such as blaCTX-M variants and, critically, blaNDM-5. Furthermore, an array of virulence factor genes was identified, with a particularly high prevalence of the toxin gene astA (68.8%, 11/16) and the bacteriocin gene cma (50.0%, 8/16), indicating pathogenic potential. This convergence of resistance and virulence in a foodborne pathogen highlights an urgent need for continuous One Health surveillance to mitigate the risks posed by these potentially untreatable “superbugs” to both animal and human health. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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30 pages, 8266 KB  
Review
Current State of the Fight Against Antimicrobial Resistance: What Are the Different Strategies for Tomorrow?
by Hicham Wahnou, Riad El Kebbaj, Béatrice Demoré, Youness Limami and Raphaël Emmanuel Duval
Antibiotics 2026, 15(6), 564; https://doi.org/10.3390/antibiotics15060564 - 1 Jun 2026
Viewed by 1021
Abstract
Antimicrobial resistance (AMR) is a leading global cause of death, with recent World Health Organization (WHO) data revealing that one in six laboratory-confirmed bacterial infections shows resistance to at least one antibiotic treatment. This review comprehensively analyzes the AMR landscape in 2026, detailing [...] Read more.
Antimicrobial resistance (AMR) is a leading global cause of death, with recent World Health Organization (WHO) data revealing that one in six laboratory-confirmed bacterial infections shows resistance to at least one antibiotic treatment. This review comprehensively analyzes the AMR landscape in 2026, detailing its evolution, mechanisms, and the innovative strategies being deployed to combat it. Driven by Darwinian selection and accelerated by factors like antibiotic overuse during the Coronavirus Disease 2019 (COVID-19) pandemic (predominantly in hospitalized patients with suspected bacterial co-infection), AMR is propelled by a diverse molecular arsenal in bacteria. Key mechanisms include enzymatic drug inactivation (e.g., the diversifying β-lactamase superfamily), target site modification (e.g., mcr genes conferring colistin resistance), efflux pumps, and biofilm formation. The rapid global spread of these traits is facilitated by a dynamic “mobilome”, a network of plasmids and transposons that shuttle resistance genes between species. This crisis has sparked a major scientific mobilization. Advances include the discovery of novel antibiotic scaffolds like lariocidin and the regulatory approval of critical new antibiotic/inhibitor combinations such as sulbactam/durlobactam and aztreonam/avibactam, which target highly resistant Gram-negative bacteria. Moreover, the first-in-class antibiotic gepotidacin offers a new option for urinary tract infections. Beyond traditional drugs, the pipeline is diversifying to include phage therapy, antivirulence strategies, and artificial intelligence-guided drug discovery. This diversification is critical as it helps preserve the effectiveness of existing Medically Important Antimicrobials (MIAs), those deemed essential for human medicine, by providing alternative or adjunctive treatment options. However, scientific innovation alone is insufficient. This review argues that lasting success requires parallel progress in global policy and infrastructure. Strategic priorities beyond 2026 must include finalizing and funding updated global action plans, strengthening real-time surveillance and diagnostic capacity, especially in low-resource settings, and implementing new economic models to de-risk antibiotic development. Embedding effective antimicrobial stewardship within universal health coverage and pandemic preparedness plans is crucial. Ultimately, defeating AMR demands an unprecedented, coordinated global effort that outpaces the relentless adaptability of bacterial pathogens. Full article
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21 pages, 7924 KB  
Article
Genomic and GWAS-Based Insights into Antimicrobial Resistance in Shewanella algae Isolated from Penaeus monodon
by Ponsit Sathapondecha, Wichai Pornthanakasem, Timpika Thepsuwan, Pacharaporn Angthong, Wiyada Chumpol, Kamonwan Lunha, Suganya Yongkiettrakul and Wanilada Rungrassamee
Antibiotics 2026, 15(4), 405; https://doi.org/10.3390/antibiotics15040405 - 16 Apr 2026
Viewed by 937
Abstract
Background/Objectives: The emergence of antimicrobial-resistant (AMR) pathogens in aquaculture ecosystems poses a significant risk to both food security and human health. Shewanella species are recognized as significant AMR reservoirs, yet their prevalence and resistance mechanisms within a shrimp-related ecosystem remain poorly characterized. This [...] Read more.
Background/Objectives: The emergence of antimicrobial-resistant (AMR) pathogens in aquaculture ecosystems poses a significant risk to both food security and human health. Shewanella species are recognized as significant AMR reservoirs, yet their prevalence and resistance mechanisms within a shrimp-related ecosystem remain poorly characterized. This study aimed to perform a genotypic and phenotypic characterization of S. algae VK101, isolated from wild-caught black tiger shrimp (Penaeus monodon) broodstock. Methods: A complete 5.21 Mb genome was generated using a hybrid Illumina and Oxford Nanopore sequencing approach. Antimicrobial susceptibility was evaluated for 21 antibiotics via Minimum Inhibitory Concentration (MIC) testing. Comparative pangenomics and genome-wide association studies (GWAS) across 125 S. algae genomes were conducted to identify novel resistance determinants. Results: MIC analysis revealed that VK101 was resistant to ampicillin (>16 µg/mL) and colistin (8 µg/mL), while showing intermediate susceptibility to imipenem and ciprofloxacin. In silico analysis identified 205 antimicrobial resistance genes (ARGs), including a perfect hit for the fluoroquinolone resistance gene qnrA3. Notably, no mcr genes were detected. Although VK101 exhibited moderate resistance (8 µg/mL), GWAS across the broader S. algae population linked a specific lptA mutation (K140N) to high-level resistance (64 µg/mL). Other GWAS-identified genes (e.g., czcA, ampC, and oprM) likely represent indirect associations driven by genetic linkage or clade-specific markers rather than direct causal factors. Conclusions: These findings highlighted the presence of multidrug-resistant S. algae in wild-caught P. monodon broodstock, reflecting the occurrence of antimicrobial resistance in aquatic environments. Colistin resistance in these isolates was primarily mediated by chromosomal variants rather than mobile mcr elements, indicating the need for integrated genomic surveillance within the aquaculture value chain. Full article
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16 pages, 1097 KB  
Article
Inferred Mobility-Resolved Resistome Architecture Suggests Recurrent Co-Resistance Modules on a Conserved Chromosomal Backbone in Multidrug-Resistant Escherichia coli from Intensive Swine Production in Hungary
by Ádám Kerek, Balázs Nagyházi, Gergely Álmos Tornyos, Levente Hunor Husz, Máté Hetyésy, Eszter Kaszab, Enikő Fehér, Patrik Mag and Ákos Jerzsele
Antibiotics 2026, 15(4), 367; https://doi.org/10.3390/antibiotics15040367 - 2 Apr 2026
Viewed by 722
Abstract
Background: Multidrug-resistant (MDR) Escherichia coli in intensive pig production represents a persistent animal health and One Health concern. Here, we integrated quantitative phenotypic susceptibility data with whole-genome sequencing (WGS) to characterize the resistome and its inferred genomic context (chromosomal vs. plasmid-predicted contigs and [...] Read more.
Background: Multidrug-resistant (MDR) Escherichia coli in intensive pig production represents a persistent animal health and One Health concern. Here, we integrated quantitative phenotypic susceptibility data with whole-genome sequencing (WGS) to characterize the resistome and its inferred genomic context (chromosomal vs. plasmid-predicted contigs and mobile genetic element (MGE)-proximal regions) in swine-associated MDR E. coli from Hungary. Methods: A total of 203 E. coli isolates from large-scale pig farms were tested by broth microdilution. Based on resistance-oriented screening from an extended-spectrum β-lactamase (ESBL)-screen-positive pool, 116 isolates were subjected to whole-genome sequencing (WGS) as a resistance-enriched subset. Resistance determinants were annotated using the Comprehensive Antibiotic Resistance Database (CARD). Results: Resistance-oriented screening indicated frequent β-lactamase activity and ESBL screening positivity (110/203 and 127/203 isolates, respectively), consistent with strong antimicrobial selection pressure in the source population. Across the full phenotypic panel, 78/203 isolates (38.4%) met the MDR definition (non-susceptible to ≥3 antimicrobial classes), with marked between-farm variation (p < 0.001) but no age-group effect (p = 0.75). Non-β-lactam minimum inhibitory concentration (MIC) distributions showed pronounced, site-dependent high-MIC “tails”, most notably for tetracyclines, trimethoprim–sulfamethoxazole, fluoroquinolones, and colistin. In the WGS cohort (n = 116), we detected 82 distinct resistance determinants (5433 total occurrences), featuring a conserved chromosomal backbone enriched for intrinsic multidrug resistance components and lipid A modification pathways, alongside common plasmid- and MGE-associated acquired ARG modules involving tetracycline (tetA/tetB), sulfonamide/trimethoprim (sul/dfrA), aminoglycoside-modifying enzymes, and phenicol determinants (floR/cat). High-priority mobile determinants were rare but present, including mcr-1 (3/116; plasmid-associated) and plasmid-mediated quinolone resistance qnrB5 (2/116). Conclusions: Importantly, mobility/context inferences are restricted to this ESBL-screen-enriched WGS subset. Swine-associated E. coli from Hungarian large-scale farms harbors complex resistance architectures shaped by co-selection of mobile ARG modules on top of a pervasive chromosomal resistance backbone. Mobility-aware surveillance and stewardship are warranted to mitigate dissemination risks at the animal–environment–human interface. Full article
(This article belongs to the Special Issue Genomic Surveillance of Antimicrobial Resistance (AMR))
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24 pages, 8862 KB  
Article
Assessing Ecological Vulnerability and Multi-Strategic Approaches for Enhancing Ecological Efficiency: Case Study of Upper and Middle Reaches of the Yellow River Basin
by Chenyang Sun, Kaixi Liu, Yuqian Wang, Yunzheng Wang, Yuqi Li and Siyuan Liu
Land 2026, 15(4), 560; https://doi.org/10.3390/land15040560 - 29 Mar 2026
Viewed by 577
Abstract
The watershed boundaries in arid and semi-arid regions are critical zones where ecological vulnerability and socio-economic development are in severe conflict. The upper and middle reaches of the Yellow River basin are a typical example of this dilemma. Intensive land use and human [...] Read more.
The watershed boundaries in arid and semi-arid regions are critical zones where ecological vulnerability and socio-economic development are in severe conflict. The upper and middle reaches of the Yellow River basin are a typical example of this dilemma. Intensive land use and human developmental interventions in this region have severely disrupted the integrity and balance of the ecosystem. While spatially designated, networked conservation areas can effectively promote the integrity and balance of regional ecosystems, these areas may fail to capture dynamic changes in vulnerability. This study develops a “functional diagnosis-structural diagnosis-integrated optimization” framework. It integrates various scenarios to diagnose vulnerability under uncertainty and identifies bottlenecks in ecological networks. For functional diagnosis, the coupling of the sensitivity–resilience–pressure (SRP) model and the Ordered Weighted Averaging (OWA) algorithm accurately locates vulnerable areas within the regional ecosystem. In terms of structural diagnosis, the Morphological Spatial Pattern Analysis (MSPA), Minimum Cumulative Resistance model (MCR), and Circuit Theory are integrated to identify structural bottlenecks. The main findings of this study are as follows: (1) Functional Diagnosis: The coupling of SRP and OWA reveals the non-linear vulnerability responses to policy preferences and identifies areas that consistently exhibit functional vulnerability across different scenarios. (2) Structural Diagnosis: The circuit theory combined with MSPA and MCR analysis identifies 72 ecological pinch points. These bottlenecks represent the weakest structural nodes crucial for maintaining regional ecological robustness. (3) Coupled Delineation and Differentiated Restoration Strategies: High vulnerability areas identified by SRP and consistently vulnerable areas identified by OWA are combined to delineate four distinct ecological restoration units: Alpine Fragile Matrix Unit, Loess Hilly Soil Conservation Unit, Anthropogenic Pressure Pinch Point Unit, Key Structural Stepping Stone Unit. Differentiated ecological restoration strategies are proposed based on the varying sensitivity, resilience, and pressure characteristics of these units. The “functional-structural” coupled ecological vulnerability evaluation framework can precisely identify vulnerable areas. The delineated restoration units and their corresponding restoration strategies provide reference and supplementation for the protected areas system, offering transferable tools for enhancing regional ecological efficiency. Full article
(This article belongs to the Special Issue National Parks and Natural Protected Area Systems)
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49 pages, 41462 KB  
Article
Planning of Cultural Heritage Network Based on the MCR Model and Circuit Theory in Shenyang City, China
by Ou Hao, Xiaojing Mu and Zhanyu Xie
Buildings 2026, 16(7), 1311; https://doi.org/10.3390/buildings16071311 - 26 Mar 2026
Cited by 1 | Viewed by 768
Abstract
This study uses Shenyang as a case to integrate multi-source dynamic data with spatial modeling. A comprehensive resistance surface was planned using 12 indicators across the natural, built, and socio-economic dimensions, with objective weighting via the CRITIC method. A hierarchical corridor network was [...] Read more.
This study uses Shenyang as a case to integrate multi-source dynamic data with spatial modeling. A comprehensive resistance surface was planned using 12 indicators across the natural, built, and socio-economic dimensions, with objective weighting via the CRITIC method. A hierarchical corridor network was generated based on the MCR model and circuit theory, validated by chi-square goodness-of-fit tests and network structural analysis. The results indicate that socio-economic factors, particularly path activity frequency, dominate the spatial patterns of the corridors, confirming that the network captures connectivity rooted in human activity rather than simply replicating transportation infrastructure. The distribution of national, provincial, and municipal heritage sites across the three higher-importance tiers (L1–L3) shows no significant deviation from the regional baseline, validating the network’s inherent de-hierarchization capacity. Network structure analysis further confirms that this equitable network simultaneously exhibits robust connectivity. The resultant network displays a distinct core–periphery structure with a monocentric-multinuclear radial pattern, forming a four-tier corridor system (core, primary, secondary, and local) that provides an actionable framework for graded protection and targeted interventions. This study advances cultural heritage conservation from passive isolation towards proactive systemic network governance, offering a transferable pathway for the sustainable preservation of heritage in high-density urban environments. Full article
(This article belongs to the Collection Strategies for Sustainable Urban Development)
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17 pages, 2418 KB  
Article
Characterization of an Escherichia coli ST156 Isolate Harboring an IncHI2-Type Plasmid Co-Carrying blaNDM-5 and mcr-1.1 Genes from Urban Wastewater Treatment Plants in Fengxian, Shanghai
by Qingyuan Zhang, Xiaohong Xie, Lixin Tao, Jian Wang, Yuan Shi, Huangfei Sheng, Chuanlong Liu, Hongwei Zhao, Meihua Liu and Jun Feng
Antibiotics 2026, 15(3), 275; https://doi.org/10.3390/antibiotics15030275 - 6 Mar 2026
Viewed by 850
Abstract
Background: The emergence of carbapenem-resistant enterobacteriaceae (CRE) co-harboring the mcr-1.1 gene and carbapenemase-encoding genes poses a severe threat to public health. Urban wastewater treatment plants (WWTPs) act as natural reservoirs and hotspots for the dissemination of antimicrobial resistance genes (ARGs). This study [...] Read more.
Background: The emergence of carbapenem-resistant enterobacteriaceae (CRE) co-harboring the mcr-1.1 gene and carbapenemase-encoding genes poses a severe threat to public health. Urban wastewater treatment plants (WWTPs) act as natural reservoirs and hotspots for the dissemination of antimicrobial resistance genes (ARGs). This study aimed to elucidate the molecular characteristics of CRE carrying mcr-1.1 in urban WWTPs. Methods: Samples were collected from the influent of urban WWTPs in Fengxian, Shanghai, from April 2024 to March 2025. mcr-1.1-positive Escherichia coli (E. coli) isolates were screened using real-time PCR, and their antimicrobial susceptibility was determined via the broth microdilution method. Plasmid conjugation assays were performed with E. coli C600 as the recipient strain. Whole-genome sequencing (WGS) was carried out to analyze the molecular characteristics of mcr-1.1-positive E. coli isolates. Results: A total of 312 samples were collected, and 5 (1.6%) mcr-1.1-positive E. coli isolates were identified. All isolates were multidrug-resistant (MDR) but susceptible to tigecycline (TIG). WGS of strain EC0176 (sequence type 156 [ST156], enteroaggregative E. coli [EAEC]) detected the presence of blaNDM-5, blaTEM-1, blaCTX-M-55, and mcr-1.1 as well as related virulence genes. Further analysis revealed that pEC0176 was an IncHI2-type plasmid co-harboring mcr-1.1, blaNDM-5, arr-3, aph(4)-Ia, aph(3′)-Ia, aac(3)-IVa, and mph(A). The plasmid pEC0176 harbored similar backbones as p20014-MCR, p2017.03.02CC_1, pSC2017167-mcr-256k, pEC17CM13_MCR and pGDE043-mcr1, including the type IV secretion system (T4SS) and IncHI-type conjugal transfer genes. Conjugation experiments confirmed that pEC0176 could be horizontally transferred into E. coli C600, with an average transfer efficiency of 3.3 × 10−2. Phylogenetic analysis showed that the MCR-1 protein of EC0176 is closely related to that of two human-derived E. coli strains from China (GenBank accession: AVR64822.1 and WP_076611062.1). Conclusions: To our knowledge, this is the first report of E. coli ST156 carrying an IncHI2-type plasmid co-harboring mcr-1.1 and blaNDM-5 from urban WWTPs in Fengxian, Shanghai. Our findings underscore the severe status of bacterial antimicrobial resistance and emphasize the necessity of enhancing antimicrobial resistance surveillance in urban WWTPs. Full article
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31 pages, 706 KB  
Article
Applying Action Research to Developing a GPT-Based Assistant for Construction Cost Code Verification in State-Funded Projects in Vietnam
by Quan T. Nguyen, Thuy-Binh Pham, Hai Phong Bui and Po-Han Chen
Buildings 2026, 16(3), 499; https://doi.org/10.3390/buildings16030499 - 26 Jan 2026
Viewed by 639
Abstract
Cost code verification in state-funded construction projects remains a labor-intensive and error-prone task, particularly given the structural heterogeneity of project estimates and the prevalence of malformed codes, inconsistent units of measurement (UoMs), and locally modified price components. This study evaluates a deterministic GPT-based [...] Read more.
Cost code verification in state-funded construction projects remains a labor-intensive and error-prone task, particularly given the structural heterogeneity of project estimates and the prevalence of malformed codes, inconsistent units of measurement (UoMs), and locally modified price components. This study evaluates a deterministic GPT-based assistant designed to automate Vietnam’s regulatory verification. The assistant was developed and iteratively refined across four Action Research cycles. Also, the system enforces strict rule sequencing and dataset grounding via Python-governed computations. Rather than relying on probabilistic or semantic reasoning, the system performs strictly deterministic checks on code validity, UoM alignment, and unit price conformity in material (MTR), labor (LBR), and machinery (MCR), given the provincial unit price books (UPBs). Deterministic equality is evaluated either on raw numerical values or on values transformed through explicitly declared, rule-governed operations, preserving auditability without introducing tolerance-based or inferential reasoning. A dedicated exact-match mechanism, which is activated only when a code is invalid, enables the recovery of typographical errors only when a project item’s full price vector well matches a normative entry. Using twenty real construction estimates (16,100 rows) and twelve controlled error-injection cases, the study demonstrates that the assistant executes verification steps with high reliability across diverse spreadsheet structures, avoiding ambiguity and maintaining full auditability. Deterministic extraction and normalization routines facilitate robust handling of displaced headers, merged cells, and non-standard labeling, while structured reporting provides line-by-line traceability aligned with professional verification workflows. Practitioner feedback confirms that the system reduces manual tracing effort, improves evaluation consistency, and supports documentation compliance with human judgment. This research contributes a framework for large language model (LLM)-orchestrated verification, demonstrating how Action Research can align AI tools with domain expectations. Furthermore, it establishes a methodology for deploying LLMs in safety-critical and regulation-driven environments. Limitations—including narrow diagnostic scope, unlisted quotation exclusion, single-province UPB compliance, and sensitivity to extreme spreadsheet irregularities—define directions for future deterministic extensions. Overall, the findings illustrate how tightly constrained LLM configurations can augment, rather than replace, professional cost verification practices in public-sector construction. Full article
(This article belongs to the Special Issue Knowledge Management in the Building and Construction Industry)
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28 pages, 2243 KB  
Review
Colistin Resistance in Gram-Negative Bacteria: Mechanisms, Transmission, and Novel Intervention Strategies
by Shah Zeb, Arzoo Nazir, Muhammad Fazal Hameed, Sadia Ikram, Syed Zeeshan Haider Naqvi, Muhammad Shoaib, Patrick Butaye, Zhiqiang Wang, Ruichao Li and Xiaoyu Lu
Microorganisms 2026, 14(1), 173; https://doi.org/10.3390/microorganisms14010173 - 13 Jan 2026
Cited by 6 | Viewed by 2775
Abstract
Multidrug resistance (MDR) in Gram-negative bacteria is a global issue and needs to be addressed urgently. MDR can emerge through genetic mutations and horizontal gene transfer and deteriorate under antibiotic selective pressure. The emergence of resistance to last-resort antibiotics, which are used to [...] Read more.
Multidrug resistance (MDR) in Gram-negative bacteria is a global issue and needs to be addressed urgently. MDR can emerge through genetic mutations and horizontal gene transfer and deteriorate under antibiotic selective pressure. The emergence of resistance to last-resort antibiotics, which are used to treat MDR bacteria, is of particular concern. Colistin has been recognized as a last-line antibiotic for the treatment of MDR Gram-negative bacterial infections caused by Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Recently, the increasing reports of colistin resistance pose a significant threat to public health, caused by both acquired and intrinsic mechanisms. The review aimed to elucidate the trends in colistin resistance, the use of colistin in human and veterinary medicine, underlying resistance mechanisms and transmission pathways, and potential mitigation of this emerging threat through novel intervention strategies. Colistin resistance is mediated by plasmid-encoded phosphoethanolamine transferases (mcr-1 to mcr-10) and chromosomal lipid A remodeling pathways. In Escherichia coli, resistance involves mcr-1–10, acrB efflux mutations, pmrA/pmrB, arnBCADTEF, and mgrB inactivation. Klebsiella pneumoniae exhibits mcr-1, mcr-8, mcr-9, mgrB disruption and phoP/phoQ–pmrAB activation. Acinetobacter baumannii harbors mcr-1–4, while Salmonella enterica and Enterobacter spp. carry mcr variants with arnBCADTEF induction. Therapeutic options include adjunct strategies such as antimicrobial peptides, nanomaterials, therapeutic adjuvants, CRISPR-Cas9-based gene editing, probiotics, vaccines, and immune modulators to restore susceptibility. This review identified that specific and wide actions are required to handle the growing colistin resistance, including genomic surveillance, tracing novel resistance mechanisms, and the application of alternative management strategies. The One Health approach is considered a key strategy to address this growing issue. Full article
(This article belongs to the Special Issue Resistance of Gram-Negative Bacteria to Last-Resort Antibacterials)
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37 pages, 1355 KB  
Review
Risk Assessment of Chemical Mixtures in Foods: A Comprehensive Methodological and Regulatory Review
by Rosana González Combarros, Mariano González-García, Gerardo David Blanco-Díaz, Kharla Segovia Bravo, José Luis Reino Moya and José Ignacio López-Sánchez
Foods 2026, 15(2), 244; https://doi.org/10.3390/foods15020244 - 9 Jan 2026
Cited by 3 | Viewed by 1196
Abstract
Over the last 15 years, mixture risk assessment for food xenobiotics has evolved from conceptual discussions and simple screening tools, such as the Hazard Index (HI), towards operational, component-based and probabilistic frameworks embedded in major food-safety institutions. This review synthesizes methodological and regulatory [...] Read more.
Over the last 15 years, mixture risk assessment for food xenobiotics has evolved from conceptual discussions and simple screening tools, such as the Hazard Index (HI), towards operational, component-based and probabilistic frameworks embedded in major food-safety institutions. This review synthesizes methodological and regulatory advances in cumulative risk assessment for dietary “cocktails” of pesticides, contaminants and other xenobiotics, with a specific focus on food-relevant exposure scenarios. At the toxicological level, the field is now anchored in concentration/dose addition as the default model for similarly acting chemicals, supported by extensive experimental evidence that most environmental mixtures behave approximately dose-additively at low effect levels. Building on this paradigm, a portfolio of quantitative metrics has been developed to operationalize component-based mixture assessment: HI as a conservative screening anchor; Relative Potency Factors (RPF) and Toxic Equivalents (TEQ) to express doses within cumulative assessment groups; the Maximum Cumulative Ratio (MCR) to diagnose whether risk is dominated by one or several components; and the combined Margin of Exposure (MOET) as a point-of-departure-based integrator that avoids compounding uncertainty factors. Regulatory frameworks developed by EFSA, the U.S. EPA and FAO/WHO converge on tiered assessment schemes, biologically informed grouping of chemicals and dose addition as the default model for similarly acting substances, while differing in scope, data infrastructure and legal embedding. Implementation in food safety critically depends on robust exposure data streams. Total Diet Studies provide population-level, “as eaten” exposure estimates through harmonized food-list construction, home-style preparation and composite sampling, and are increasingly combined with conventional monitoring. In parallel, human biomonitoring quantifies internal exposure to diet-related xenobiotics such as PFAS, phthalates, bisphenols and mycotoxins, embedding mixture assessment within a dietary-exposome perspective. Across these developments, structured uncertainty analysis and decision-oriented communication have become indispensable. By integrating advances in toxicology, exposure science and regulatory practice, this review outlines a coherent, tiered and uncertainty-aware framework for assessing real-world dietary mixtures of xenobiotics, and identifies priorities for future work, including mechanistically and data-driven grouping strategies, expanded use of physiologically based pharmacokinetic modelling and refined mixture-sensitive indicators to support public-health decision-making. Full article
(This article belongs to the Special Issue Research on Food Chemical Safety)
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17 pages, 5577 KB  
Article
Tracking Global Transmission Dynamics of the Plasmid-Mediated mcr Gene: A Genomic Epidemiological Analysis
by Jinzhao Long, Xin Wang, Mengyue Liu, Jie Wu, Haiyan Yang, Shuaiyin Chen and Guangcai Duan
Microorganisms 2026, 14(1), 28; https://doi.org/10.3390/microorganisms14010028 - 22 Dec 2025
Viewed by 914
Abstract
The emergence and spread of mobile colistin resistance (mcr) genes pose a significant challenge in controlling multidrug-resistant Gram-negative pathogens. Understanding the epidemiology of mcr-carrying plasmids is essential for mitigating their dissemination across humans, animals, and the environment. To characterize their [...] Read more.
The emergence and spread of mobile colistin resistance (mcr) genes pose a significant challenge in controlling multidrug-resistant Gram-negative pathogens. Understanding the epidemiology of mcr-carrying plasmids is essential for mitigating their dissemination across humans, animals, and the environment. To characterize their spatiotemporal dynamics on a global scale, we analyzed an extensive collection of 5,549 mcr-carrying plasmids spanning 1995 to the present. We found that cross-genera transmission patterns of mcr-carrying plasmids varied across four distinct periods. Initially, IncHI2/HI2A plasmids provided a survival advantage across genera and regions, followed by IncI2, and ultimately by IncX4. Moreover, the three plasmid lineages (i.e., IncX4, IncI2, and IncHI2/HI2A) have reached a stable distribution across diverse bacterial hosts and geographic regions through horizontal gene transfer and clonal expansion. By integrating sequence similarity clustering of plasmids and mcr-related genetic environments, we identified 79 cross-genus, 43 intra-E. coli, and 10 intra-S. enterica transmission units. Molecular dating analysis traced the origin of IncX4 plasmids to 1990 in animal hosts, with phylogenetic evidence indicating potential cross-host, -genus, and -region exchange. Notably, IncP1 plasmids emerged as important vectors of mcr-1 and mcr-3 spread, particularly in Southeast Asia, warranting enhanced surveillance. These findings provide critical insights into the global transmission networks of plasmid-mediated mcr genes and underscore the urgent need for coordinated interventions. Full article
(This article belongs to the Special Issue Advances in Microbial Genomics in the AMR Field)
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26 pages, 3785 KB  
Systematic Review
One Health Antimicrobial Resistance in Qatar: A Comprehensive Systematic Review and Meta-Analysis of Animal, Food, and Environmental Reservoirs
by Lubna I. Abu-Rub, Ristha Kamar, Cut Salsabila Fatin, Susu M. Zughaier and Nahla O. Eltai
Antibiotics 2025, 14(12), 1219; https://doi.org/10.3390/antibiotics14121219 - 3 Dec 2025
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Abstract
Background: Antimicrobial resistance (AMR) is a global threat that extends beyond clinical settings, impacting animals, food, and the environment. To the best of our knowledge, this review presents the first systematic evaluation of AMR and antimicrobial resistance genes (ARGs) in non-human sources [...] Read more.
Background: Antimicrobial resistance (AMR) is a global threat that extends beyond clinical settings, impacting animals, food, and the environment. To the best of our knowledge, this review presents the first systematic evaluation of AMR and antimicrobial resistance genes (ARGs) in non-human sources in Qatar, using a One Health framework. Methods: Following PRISMA 2020 guidelines, we searched five major databases: PubMed, Scopus, Web of Science, Embase, Google Scholar (only 3 pages) and QRDI, without date restrictions for studies on AMR and ARGs in animals, food, and environmental sources in Qatar. Only primary studies from Qatar reporting phenotypic or genotypic AMR/ARG data in animals, food, or the environment were included; all human-focused, non-Qatar, or non-primary research were excluded. Eligible studies were screened and analyzed using GraphPad Prism 10.4 and StatsDirect, applying random- or fixed-effects models based on heterogeneity and assessed for quality using the JBI checklist for prevalence. Results: Fifteen eligible studies published up to 2025 were included. Escherichia coli was the most frequently reported organism. High resistance rates were observed in the Access group antibiotics, such as ampicillin (0.50; 95% CI: 0.47–0.53) and tetracycline (0.50; 95% CI: 0.45–0.55), as well as in the Watch group antibiotics, including ciprofloxacin (0.40; 95% CI: 0.36–0.44) and fosfomycin (0.26; 95% CI: 0.20–0.32). Resistance to Reserve group antibiotics was comparatively lower, with pooled estimates of 0.14 (95% CI: 0.08–0.20) for colistin and 0.11 (95% CI: 0.05–0.25) for carbapenems, though lower, remains concerning. The overall pooled estimate for multidrug resistance (MDR) was 0.56 (95% CI: 0.36–0.72), and poultry was identified as the main reservoir, particularly to Critically Important Antimicrobials (CIAs). ARGs, including blaCTX-M, blaTEM, mcr-1, and qnr, were detected across all sectors, with wastewater showing a notable ARG burden. Data on other livestock species remain limited. Limitations include a few studies, variable quality, and inconsistent methods affecting comparability and precision. Conclusions: This review highlights significant AMR and ARG prevalence in non-human sources in Qatar and underscores the urgent need for a national One Health surveillance strategy incorporating WHO AWaRe and CIA frameworks to address this escalating public health threat. Full article
(This article belongs to the Special Issue Antibiotic Resistance: A One-Health Approach, 2nd Edition)
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25 pages, 1363 KB  
Review
The Public Health Risks of Colistin Resistance in Dogs and Cats: A One Health Perspective Review
by Juliana Menezes, Laura Fernandes, Cátia Marques and Constança Pomba
Antibiotics 2025, 14(12), 1213; https://doi.org/10.3390/antibiotics14121213 - 2 Dec 2025
Cited by 2 | Viewed by 1366
Abstract
Colistin, a polymyxin antibiotic considered a last-line treatment for multidrug-resistant Gram-negative infections, has been widely used in livestock, promoting resistance in bacterial populations that can disseminate through the environment. Although rarely used in companion animals, dogs and cats can acquire and spread colistin-resistant [...] Read more.
Colistin, a polymyxin antibiotic considered a last-line treatment for multidrug-resistant Gram-negative infections, has been widely used in livestock, promoting resistance in bacterial populations that can disseminate through the environment. Although rarely used in companion animals, dogs and cats can acquire and spread colistin-resistant strains through shared environments, acting as potential reservoirs of resistance. Reliable detection of resistant strains remains challenging due to technical limitations of routine susceptibility tests. Despite these constraints, epidemiological studies demonstrate the global presence of colistin-resistant bacteria in companion animals, with multiple plasmid-mediated colistin-resistant genes (mcr) identified in different bacteria species. Evidence of clonal and plasmid-mediated sharing of resistant strains between companion animals, humans, and, in some cases, food-producing animals highlights the complex and multidirectional nature of transmission. Although the directionality of transmission remains difficult to establish, the detection of colistin-resistant bacteria in companion animals is concerning. Addressing this challenge requires a One Health approach, integrating coordinated surveillance and infection and control measures in veterinary practices to safeguard the effectiveness of this critical last-resort antibiotic. This review summarizes current knowledge on colistin resistance mechanisms, diagnostic challenges, epidemiology, and the potential for interhost transmission, highlighting the role of dogs and cats as potential reservoirs of colistin resistance. Full article
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