Search Results (1,266)

Background: Although surgical antibiotic prophylaxis (SAP) is considered a standard of care for preventing surgical site infections, the rising incidence of antimicrobial resistance (AMR) increases the likelihood of infections caused by multidrug-resistant organisms (MDROs), which may be associated with worse surgical outcomes. Methods: A multidisciplinary working group was convened by the Italian Multidisciplinary Society for the Prevention of Healthcare-Associated Infections (SIMPIOS) to define key measures for optimizing SAP in the era of AMR. Selecting the most appropriate SAP in patients colonized with MDROs is a complex decision that cannot be generalized, as it depends on both host factors and the specific surgical procedure. At present, there is limited evidence of SAP in these patients. Results: This position paper aims to provide practical guidance for optimizing SAP in the context of an AMR era. It is structured in three sections: (1) core principles of surgical antibiotic prophylaxis; (2) the role of screening, decolonization, and targeted prophylaxis for MDROs; and (3) barriers to changing surgeons’ prescribing behaviours. Conclusions: The working group developed 15 recommendation statements based on scientific evidence. Full article

RNA interference (RNAi) is a powerful mechanism of post-transcriptional gene regulation in which small interfering RNA (siRNA) is utilized to target and degrade specific RNA sequences. In this study, experiments were conducted to evaluate the efficacy of combination siRNA therapy against enterovirus 71 (EV71) and the potential of this therapy to delay or prevent the emergence of resistance in vitro. siRNAs targeting multiple genes of EV71 were designed, and the effects of a cocktail of siRNAs on viral replication were assessed compared to those of single-siRNA treatment. Cotransfection of multiple siRNAs targeting different protein-coding genes of the EV71 genome effectively suppressed escape mutants resistant to RNAi. Combination therapy with siRNAs targeting multiple viral genes successfully prevented viral escape mutations over five passages. By contrast, serial passaging with a single siRNA led to the rapid emergence of resistance, with mutations identified in the siRNA target sites. The combination of siRNAs specifically targeting different regions demonstrated an additive effect and was more effective than individual siRNAs at inhibiting EV71 replication. This study supports the effectiveness of combination therapy using siRNAs targeting multiple genes of EV71 to inhibit viral replication and prevent the emergence of resistant escape mutants. Overall, the findings identify RNAi targeting multiple viral genes as a potential strategy for therapeutic development against viral diseases and for preventing the emergence of escape mutants resistant to antiviral RNAi. Full article

Chromium (Cr), a toxic heavy metal, poses significant environmental and health risks when industrial effluents containing Cr are discharged untreated. Addressing this challenge, this study developed a selective chromium removal strategy using IRA-900 resin in a sulfuric acid system with sodium phosphite (NaH₂PO₃) as a complexing agent. In the NaH₂PO₃-H₂SO₄ system, IRA-900 resin exhibited exceptional selectivity for Cr³⁺ with minimal co-adsorption of competing ions. The adsorption process followed the Langmuir isotherm model (R² > 0.99), indicating monolayer chemisorption dominated by homogeneous active sites, and achieved a maximum capacity of 103.56 mg·g⁻¹. Characterization via XPS, FT-IR, and SEM-EDS revealed a two-step mechanism: Cr³⁺ reacts with H₂PO₃⁻ to form an anionic complex, and then the complex undergoes electrostatic interaction and ion exchange with chloride ions (Cl⁻) on the quaternary ammonium groups of the resin. The chromium-loaded resin demonstrated remarkable structural stability, resisting Cr³⁺ desorption under conventional elution conditions. This property provides a novel pathway for chromium solidification in industrial wastewater, effectively minimizing secondary pollution risks. This work advances the design of ligand-assisted ion-exchange systems for targeted heavy metal removal, offering both high selectivity and environmental compatibility in wastewater treatment. Full article

Background: Antibody-drug conjugates (ADCs) have ushered in a new era of precision oncology by combining the targeting specificity of monoclonal antibodies with the potent cytotoxicity of chemotherapeutic drugs. However, the cellular and molecular mechanisms underlying their dose-limiting ocular toxicity remain unclear. Elahere™, the first FDA-approved ADC targeting folate receptor α (FRα), demonstrates remarkable efficacy in platinum-resistant ovarian cancer but causes keratitis and other ocular toxicities in some patients. Notably, FRα is not expressed in the corneal epithelium—the primary site of damage—highlighting the urgent need to elucidate its underlying mechanisms. The aim of this study was to identify the cell-type-specific molecular mechanisms underlying Elahere-induced ocular toxicity. Methods: Sprague-Dawley rats were treated with intravenous Elahere (20 mg/kg) or vehicle weekly for five weeks. Ocular toxicity was determined by clinical examination and histopathology. Corneal single-cell suspensions were analyzed using the BD Rhapsody single-cell RNA sequencing (scRNA-seq) platform. Bioinformatic analyses to characterize changes in corneal cell populations, gene expression, and signaling pathways included cell clustering, differential gene expression, pseudotime trajectory inference, and cell-cell interaction modeling. Results: scRNA-seq profiling of 47,606 corneal cells revealed significant damage to the ocular surface and corneal epithelia in the Elahere group. Twenty distinct cell types were identified. Elahere depleted myeloid immune cells; in particular, homeostatic gene expression was suppressed in phagocytic macrophages. Progenitor populations (limbal stem cells and basal cells) accumulated (e.g., a ~2.6-fold expansion of limbal stem cells), while terminally differentiated cells decreased in corneal epithelium, indicating differentiation blockade. Endothelial cells exhibited signs of injury and inflammation, including reduced angiogenic subtypes and heightened stress responses. Folate receptor alpha, the target of Elahere, was expressed in endothelial and stromal cells, potentially driving stromal cells toward a pro-fibrotic phenotype. Fc receptor genes were predominantly expressed in myeloid cells, suggesting a potential mechanism underlying their depletion. Conclusions: Elahere induces complex, multi-compartmental ocular toxicity characterized by initial perturbations in vascular endothelial and immune cell populations followed by the arrest of epithelial differentiation and stromal remodeling. These findings reveal a cascade of cellular disruptions and provide mechanistic insights into mitigating Elahere-associated ocular side effects. Full article

Background/Objectives: The herbicide resistance of blackgrass (Alopecurus myosuroides Huds.) is one of the most serious problems in the winter cereal monoculture in Europe. Recently, Greek farmers expressed complaints of reduced susceptibility of this weed to winter wheat herbicides. Keeping this in mind, this study focused on the investigation of blackgrass resistance to herbicides at both phenotypic and molecular levels. Methods: Whole-plant rate-response pot assays were conducted to study the possible evolution of resistance (cross- or multiple-resistance) in a blackgrass population to ACCase- and ALS-inhibiting herbicides. Analysis of the ACCase gene sequence, herbicide metabolism study and competition with winter wheat studies were also conducted. Results: High levels of cross-resistance mainly to the ACCase post-emergence clodinafop-propargyl, medium to fenoxaprop-P-ethyl, cycloxydim, pinoxaden, as well as lower levels of resistance to ALS-inhibitors (mesosulfuron-methyl + iodosulfuron-methyl-sodium and pyroxsulam) were confirmed. In addition, the pre-emergence soil-applied herbicides chlorotoluron + diflufenican and prosulfocarb provided excellent control of the S and R blackgrass populations. The analysis of the ACCase gene sequence revealed a point mutation at position 1781, resulting in an amino acid substitution from isoleucine (Ile) to leucine (Leu). Furthermore, the combined application of the herbicides with piperonyl butoxide (PBO, applied 2 h before herbicide application) indicated that there was herbicide metabolism, which may be mediated by cytochrome P450. The R blackgrass population, when grown in competitive interaction with winter wheat, produced more tillers and aboveground fresh weight compared to the S population and caused greater reduction in winter wheat. Conclusions: The results suggest that a blackgrass population has developed multiple resistance to ACCase- and ALS-inhibiting herbicides, due to ACCase gene mutation and herbicide metabolism. No fitness cost and no compromised competitive ability associated with the blackgrass resistance were observed. Full article

Acinetobacter baumannii is an opportunistic pathogen associated with severe bloodstream infections. It exhibits a high level of multidrug resistance, posing major clinical challenges. Antisense peptide nucleic acids (PNAs) represent a promising alternative to conventional antibiotics; however, their therapeutic efficacy depends on optimal delivery and molecular design. In this study, we aimed to enhance the antibacterial activity of PNAs against A. baumannii by systematically optimizing cell-penetrating peptides (CPPs), PNA length, target region, and chemical modifications. The efficacy and safety of CPP–PNA constructs were evaluated using a comprehensive set of approaches, including determination of minimum bactericidal and minimum inhibitory concentrations, quantitative reverse transcription polymerase chain reaction, Western blotting, and cytotoxicity assays. Three CPP–PNA constructs targeting carA were synthesized. Among these, the KFFK (FFK)₂–PNA conjugate showed the strongest bacterial growth-inhibitory effect, while the addition of extra lysine residues reduced its efficacy. Further analyses showed that a 10-mer alpha (α)-PNA modification targeting the ribosomal binding site of carA had the greatest inhibitory effect. These results underscore the importance of rational CPP design and PNA optimization in developing effective antisense antimicrobials against A. baumannii. Full article

Background/Objectives: Escherichia coli is one of the leading causes of surgical site infections (SSIs) and poses a growing public health concern due to its increasing antimicrobial resistance. High rates of extended-spectrum beta-lactamase (ESBL) production among E. coli strains complicate treatment outcomes and emphasize the need for effective surveillance and control strategies. Methods: A total of 691 E. coli isolates from general surgery clinics (2020–2025) were identified using MALDI-TOF MS. Antibiotic susceptibility data and patient variables were cleaned, encoded, and used to predict resistance using the Random Forest, CatBoost, and Naive Bayes algorithms. SMOTE addressed class imbalance, and model performance was assessed through various validation methods. Results: Among the three machine learning models tested, Random Forest (RF) showed the best performance in predicting antibiotic resistance of E. coli, achieving median accuracy, precision, recall, and F1-scores of 0.90 and AUC values up to 0.99 for key antibiotics. CatBoost performed similarly but was less stable with imbalanced data, while Naive Bayes showed lower accuracy. Feature importance analysis highlighted strong inter-antibiotic resistance links, especially among β-lactams, and some influence of demographic factors. Conclusions: This study highlights the potential of simple, high-performing models using structured clinical data to predict antimicrobial resistance, especially in resource-limited clinical settings. By incorporating machine learning into antimicrobial resistance (AMR) surveillance systems, our goal is to support the advancement of rapid diagnostics and targeted antimicrobial stewardship approaches, which are essential in addressing the growing challenge of multidrug resistance. Full article

Background: Mycobacterium avium (Mav) is a leading cause of pulmonary disease among non-tuberculous mycobacteria (NTMs) due to its extensive antibiotic resistance profile. The essential Rel protein is a bifunctional enzyme, which is sensitive to environmental stress and regulates cellular guanosine-3′,5′-bispyrophosphate ((p)ppGpp). Increased levels of the alarmone thereby initiate a survival response, contributing to bacterial persistence and virulence. Objectives: MavRel harbors an unusual extension at the N-terminal domain (NTD), which we aim to characterize its possible regulatory role in maintaining (p)ppGpp homeostasis. We also studied whether the TGS domain retains its regulation capacity in MavRel and the binding propensity of the ACT domain to valine. Methods: Molecular dissection of MavRel was performed to generate a series of truncates to quantify the synthetase and hydrolase activities. Binding experiments with tRNA and valine were carried out via tryptophan quenching assay and NMR, respectively. Results: Bi-catalytic regulation of MavRel was found to be predominantly governed by the residues 37–50 at the NTD extension in its free state. The TGS domain was shown to harbor the capacity to bind with deacylated tRNA and represses synthetase activity to a lower degree compared to the NTD extension. We also characterized the dimeric Mav ACT-domain and the interacting residues contributing to its affinity with valine to function as a nutrient sensor. Conclusions: The mapping of the unique NTD regulatory element of MavRel reveals its functional relevance to coordinate the catalytic states of synthetase and hydrolase, hence underscores the prospect to drive inhibitor development targeting this novel site against Mav infections. Full article

Background: Drug resistance (DR) mediated by ABC transporters in the cytoplasmic membrane has been one of the best studied mechanisms of DR in vitro. More recently, it has also been suggested that ABC transporters expressed on lysosomal membranes could increase the sequestration of anticancer drugs in lysosomes, thereby reducing their concentration at target sites, and causing DR. Unfortunately, convincing evidence that such a DR mechanism actually exists is lacking, even in the case of in vitro experiments. Methods: This hypothetical study using simplified models evaluates the effect of ABC transporter-mediated accumulation of anticancer drugs in lysosomes on their concentration at target sites under standard in vitro conditions. Results: Calculations show that an ABC transporter resident on the plasma membrane must create and maintain a relatively small concentration gradient between extracellular space and the target site to reduce the drug concentration at the target site by, for example, half. In contrast, if a lysosomal ABC transporter is to also halve the concentration of the drug at the target site, then it must create and maintain a huge concentration gradient between lysosomes and target sites. It is very likely that massive accumulation of drugs in lysosomes would have a negative effect on the function of the lysosomes themselves. Conclusions: The results of this hypothetical study strongly suggest that the mechanism of DR mediated by lysosomal ABC transporters is questionable, as it requires enormous accumulation of the drug in lysosomes, which would likely also impair their function. Therefore, it is highly unlikely that this hypothetical DR mechanism could actually be utilized by tumor cells to defend against the cytotoxic effects of chemotherapy in vitro. Full article

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and the lung is one of the most frequent metastatic sites for HCC. In this study, we aimed to identify a mild active substance in Morus alba L. that can inhibit the pulmonary metastasis of HCC and reduce the drug resistance of clinical therapies. Further deepen the understanding of the anti-cancer functions of the mulberry active substances. In this study, we have screened and identified a flavonoid compound extracted from the root bark of the Morus alba L. named Kuwanon A (KA). Our research demonstrated that KA directly targeted the YWHAB (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta) and mediated its dimer dissociation. Thereby inhibiting the MAPK pathway and affecting downstream biological functions, including cell cycle arrest and migration/invasion inhibition. The experiment results proved that KA could inhibit the proliferation and metastasis of highly metastatic HCC cells both in vitro and in vivo. Additionally, when KA was combined with the clinical drug sorafenib, it exhibited a synergistic effect in inhibiting HCC cell proliferation, migration, and invasion. In conclusion, KA demonstrated a favorable anti-tumor effect in HCC cells. Full article

Drought stress critically constrains agricultural productivity in arid and semi-arid regions, necessitating the development of drought-tolerant crop varieties for sustainable food security. This study evaluated drought tolerance in 222 foxtail millet (Setaria italica) germplasms from diverse Chinese agroecological zones from 2021–2023 at a specialized identification site in Xinjiang. Field experiments used a randomized complete block design comparing normal irrigation (3000 m³/ha) with drought stress (1800 m³/ha) across 12 morpho-agronomic traits including plant height, spike characteristics, biomass, and yield components. Drought stress significantly reduced all parameters, with yield exhibiting the highest sensitivity (drought tolerance coefficient = 0.58). Principal component analysis indicated that the first three components explained 82.70% of phenotypic variance, with yield-related parameters contributing the most to genotypic differentiation. Integrated evaluation using comprehensive drought tolerance coefficient (DTC), drought resistance index (DRI), and D-values classified germplasms into five categories: highly resistant (4.50%), resistant (11.71%), moderately resistant (57.21%), sensitive (16.22%), and highly sensitive (10.36%). Correlation and stepwise regression analyses identified five critical indicators: stem basal thickness, single plant biomass, spike weight, grain weight per spike, and yield. The predictive model demonstrated exceptional accuracy (R² = 0.9998), enabling efficient screening using the targeted traits. The elite germplasms T125 (92) and Baogu 23 (135) consistently ranked as the most drought-tolerant across all methods. These findings establish a robust methodological framework for evaluating drought tolerance in foxtail millet and provide practical selection criteria for developing climate-resilient cultivars. The identified germplasms and evaluation indices significantly contribute to agricultural sustainability in water-limited environments, supporting food security in regions that are increasingly affected by climate-induced drought stress. Full article

Eryngium foetidum L. belongs to the Apiaceae family and is a perennial herb. The entire plant is rich in essential oils, which have a distinctive aroma similar to cilantro. This plant exhibits significant biological activity and possesses characteristics such as disease resistance and antimicrobial properties, showing great potential in medical and food applications. Additionally, its essential oil has substantial commercial value. Mitochondria play a crucial role as organelles within plant cells; however, the mitochondrial genome of E. foetidum remains underexplored. To fill this research gap, we conducted sequencing and assembly of the mitochondrial genome of E. foetidum, aiming to uncover its genetic mechanisms and evolutionary trajectories. Our investigation reveals that the mitochondrial genome of E. foetidum is a circular structure, similar to that of other species, with a length of 241,660 bp and a GC content of 45.35%, which is within the range observed in other organisms. This genome encodes 59 genes, comprising 37 protein-coding sequences, 18 tRNA genes, and 4 rRNA genes. Comparative analysis highlighted 16 homologous regions between the mitochondrial and chloroplast genomes, with the longest segment spanning 992 bp. By analyzing 37 protein-coding genes (PCGs), we identified 479 potential RNA editing sites, which induce the formation of stop codons in the nad3 and atp6 genes, as well as start codons in the ccmFC, atp8, nad4L, cox2, cox1, and nad7 genes. Meanwhile, the genome shows a preference for A/T bases and A/T-ending codons, with 32 codons having a relative synonymous codon usage (RSCU) value greater than 1. The codon usage bias is relatively weak and mainly influenced by natural selection. Most PCGs are under purifying selection (Ka/Ks < 1), while only a few genes, such as rps7 and matR, may be under positive selection. Phylogenetic analysis of mitochondrial PCGs from 21 species showed E. foetidum at the basal node of Apiaceae, consistent with the latest APG angiosperm classification and chloroplast genome-based phylogenetic relationships. In summary, our comprehensive characterization of the E. foetidum mitochondrial genome not only provides novel insights into its evolutionary history and genetic regulation but also establishes a critical genomic resource for future molecular breeding efforts targeting mitochondrial-associated traits in this economically important species. Full article

Background/Objectives: Understanding variabilities in the Major Histocompatibility Complex class I (MHC I) gene is essential for evaluating immunogenetic diversity in clariid catfish. MHC I plays a critical role in immune defense by presenting endogenous antigens to cytotoxic T cells. Therefore, we aimed to investigate the genetic diversity, selection patterns, and phylogenetic relationships of MHC I alleles in three important clariid catfish species (Clarias gariepinus, Clarias macrocephalus, and Clarias batrachus) across wild and hatchery populations in Thailand. Methods: Targeted next-generation sequencing of a 174 bp fragment partial exon 6 of MHC I-UAA gene was performed, along with phylogenetic analyses, neutrality tests and dN/dS analyses. Results: Overall, 91 novel alleles were identified in 674 individuals, all of which were novel (100% novelty), with none matching existing reference sequences, thereby revealing extensive variation in population-specific variants. Phylogenetic analyses revealed allele sharing among species, which was consistent with balanced selection. Neutrality tests and dN/dS analyses provided evidence of both purifying and diversifying selection, with episodic positive selection detected at multiple codon sites associated with the antigen-binding α1 domain. Distinct selection patterns among populations, influenced by local environmental conditions and human pressures, along with high allele richness, are reflected in the diversity of immunogenetic variations. Conclusions: These findings provide critical insights into immune adaptation and highlight the potential of MHC I as a functional marker for genetic monitoring. Although a causal relationship between MHC I polymorphism and disease resistance is debated, studies suggest associations with pathogen survival, indicating future implications for aquaculture breeding and conservation, particularly in marker-assisted selection for broodstock management in Thailand. Full article

The undesirable properties of bioactive substances (such as poor solubility and low stability) and various barriers in the gastrointestinal tract (gastric acid, digestive enzymes, mucus and intestinal epithelial cells) hinder their absorption and utilisation by the human body. Nanodelivery systems have been proven to effectively address the above problems, particularly targeted nanodelivery systems, which have more advantages in improving the bioavailability of bioactive substances. However, many studies have not included all barriers. Furthermore, given that the small intestine is the main site for the absorption of bioactive substances in the human body, this review primarily discusses targeted nanodelivery systems designed for the gastrointestinal barrier and summarises how to construct a nanodelivery system that can resist the adverse effects of the gastrointestinal tract and target the small intestine for the absorption of bioactive substances. This paper proposes that the ideal system is the active targeted nanodelivery system that targets enterocytes and its future development trend is discussed. This review aims to provide new insights for the rational design of nanodelivery platforms that efficiently target the small intestine and promote the absorption of bioactive substances, as well as promote the development of fields such as personalised nutrition and nutritional intervention. Full article

Malaria persists as a paradigmatic model of co-evolutionary complexity, emerging from the dynamic interplay among a human host, Anopheles vectors, and Plasmodium falciparum parasites. In human populations, centuries of selective pressures have sculpted an intricate and heterogeneous immunogenetic landscape. Classical adaptations, such as hemoglobinopathies, are complemented by a diverse array of genetic polymorphisms that modulate innate and adaptive immune responses. These genetic traits, along with the acquisition of functional immunity following repeated exposures, mitigate disease severity but are continually challenged by the parasite’s highly evolved mechanisms of antigenic variation and immunomodulation. Such host adaptations underscore an evolutionary arms race that perpetually shapes the clinical and epidemiological outcomes. Intermediaries in malaria transmission have evolved robust responses to both natural and anthropogenic pressures. Their vector competence is governed by complex polygenic traits that affect physiological barriers and immune responses during parasite development. Recent studies reveal that these mosquitoes exhibit rapid behavioral and biochemical adaptations, including shifts in host-seeking behavior and the evolution of insecticide resistance. Mechanisms such as enhanced metabolic detoxification and target site insensitivity have emerged in response to the widespread use of insecticides, thereby eroding the efficacy of conventional interventions like insecticide-treated bed nets and indoor residual spraying. These adaptations not only sustain transmission dynamics in intervention saturated landscapes but also challenge current vector control paradigms, necessitating the development of innovative, integrated management strategies. At the molecular level, P. falciparum exemplifies evolutionary ingenuity through extensive genomic streamlining and metabolic reconfiguration. Its compact genome, a result of strategic gene loss and pruning, is optimized for an obligate parasitic lifestyle. The repurposing of the apicoplast for critical anabolic functions including fatty acid, isoprenoid, and haem biosynthesis highlights the parasite’s ability to exploit host derived nutrients efficiently. Moreover, the rapid accumulation of mutations, coupled with an elaborate repertoire for antigenic switching and epigenetic regulation, not only facilitates immune escape but also accelerates the emergence of antimalarial drug resistance. Advanced high throughput sequencing and functional genomics have begun to elucidate the metabolic epigenetic nexus that governs virulence gene expression and antigenic diversity in P. falciparum. By integrating insights from molecular biology, genomics, and evolutionary ecology, this study delineates the multifaceted co-adaptive dynamics that render malaria a recalcitrant global health threat. Our findings provide critical insights into the molecular arms race at the heart of host–pathogen vector interactions and underscore promising avenues for the development of next generation therapeutic and vector management strategies aimed at sustainable malaria elimination. Full article