Search Results (2,217)

As a representative form of extreme weather, typhoons inflict widespread and systemic damage, posing a severe threat to the livestock industry. The stress they induce, typhoon stress (TS), is an unavoidable and complex environmental challenge that severely disrupts the ovarian function of Wenchang chickens. In this preliminary study, we employed a two-group comparison design (n = 6 per group) integrating behavioral observations, serum biochemical assays, histopathological examinations, and molecular analyses (qPCR, 16S rDNA sequencing, and transcriptome sequencing) to explore the role of the microbiota–gut–brain–ovarian axis (MGBOA) in this process. The findings revealed that TS markedly reduced water intake and locomotor activity, while it elevated serum corticosterone (CORT) and oxidative stress markers. It also induced shifts in gut microbiota composition, including a decrease in Bacteroides and an increase in Escherichia–Shigella. Furthermore, TS compromises duodenal intestinal barrier integrity, as evidenced by downregulation of the tight junction proteins TJP1 and CLDN1, structural damage to intestinal villi, and a reduced villus-to-crypt ratio. In the hypothalamus, VIP mRNA expression was upregulated, while GHSR expression was downregulated; the expression of the tight junction protein CLDN5 was also reduced. In the ovary, reproductive potential was suppressed, manifested by a reduction in follicle number and downregulation of STAR expression. Ovarian transcriptome analysis highlighted enrichments in pathways associated with inflammation (e.g., Toll-like receptor signaling) and lipid metabolism (e.g., PPAR signaling). These results support the hypothesis that TS impairs egg production via the MGBOA, providing preliminary mechanistic insights into how environmental stressors might disrupt animal productivity through MGBOA-mediated pathways. Full article

To reveal how the characteristic flavor of jasmine tea is generated, this study analyzed the coordinated changes in sensory properties, chemical components, and aroma migration behavior during scenting. Sensory evaluation, biochemical assays, and headspace solid-phase microextraction–gas chromatography–mass spectrometry (HS-SPME-GC-MS) integrated with orthogonal partial least squares discriminant analysis (OPLS-DA) and relative odor activity value (rOAV) filtering were applied to tea samples before and after scenting. After scenting, aroma and taste scores increased significantly, and liquor color shifted from tender green to pale yellow. Amino acids and soluble sugars increased, while astringent substances such as tea polyphenols and catechins decreased. Key floral compounds, including cis-3-hexenyl benzoate and methyl anthranilate, were transferred from jasmine flowers to the tea base and enriched, likely contributing to the typical aroma profile. The retention rate of aroma in spent flowers was positively correlated with hydrophobicity (logP, r > 0.46, p < 0.01) and negatively with polarity (TPSA, r > −0.42, p < 0.05), suggesting regulation by hydrophobic partitioning. In contrast, aroma transfer to the tea base showed no simple correlation with any single physicochemical parameter, suggesting multi-factor regulation. This study provides insights into the scenting process and offers a theoretical reference for quality control in jasmine tea production. Full article

Highland barley (Hordeum vulgare var. nudum), a member of the genus Hordeum in the family Poaceae, represents a unique cultivated crop adapted to the Qinghai–Tibet Plateau. Weed infestation has long posed a serious threat to the yield and quality of highland barley, and the lack of effective weed management strategies has become a major constraint in its production. Pyroxsulam is an acetolactate synthase (ALS)-inhibiting herbicide widely used for weed control in highland barley fields. This study investigated the molecular mechanisms underlying the response of highland barley to pyroxsulam by integrating physiological, biochemical, and transcriptomic analyses. ALS activity assays showed that the resistant variety ‘Qing0306’ exhibited a significant increase in relative ALS activity within 1–4 days after pyroxsulam treatment. qRT-PCR analysis revealed a rapid induction of HvnALS expression, which was significantly higher in ‘Qing0306’ than in ‘Qing0160’ on the first day after treatment (p < 0.01), indicating that resistance is primarily associated with target-enzyme overexpression rather than target-site mutations. Moreover, transgenic Arabidopsis lines overexpressing HvnP450 and HvnGSTs displayed enhanced tolerance to pyroxsulam, as evidenced by an increased root length and fresh weight compared with wild-type plants. This study provides mechanistic insights that support the genetic improvement of pyroxsulam-resistant highland barley. Full article

Polyamines, putrescine, spermidine and spermine, are essential polycationic metabolites present in all eukaryotic cells, where they regulate fundamental processes including nucleic acid stabilization, translation, and stress responses. Spermidine synthase (SPDS), a member of the aminopropyltransferase (APT) family, catalyzes the transfer of an aminopropyl group from decarboxylated S-adenosylmethionine (dc-SAM) to putrescine to form spermidine. Although genomic analyses predict the presence of SPDS homologs in multiple fungal species, polyamine biosynthesis has not been experimentally characterized in the multidrug-resistant fungal pathogen Candidozyma auris. Here, we report the biochemical and functional characterization of the C. auris spermidine synthase, CauSpe3. The CauSPE3 gene complemented a Saccharomyces cerevisiae spe3Δ mutant demonstrating conserved function in vivo. Recombinant CauSpe3 was expressed in Escherichia coli, purified and analyzed using the fluorescence-based DAB-APT assay, which uses 1,2-diacetylbenzene (DAB) for polyamine detection. CauSpe3 catalyzed efficient conversion of putrescine to spermidine in the presence of dc-SAM, with K_half values of 65.5 ± 7.11 µM for putrescine and 66.9 ± 2.09 µM for dc-SAM, and V_max values of 7.1 ± 0.57 and 7.9 ± 0.12 nmol·µg⁻¹·min⁻¹, respectively. A catalytic-site mutant and heat-inactivated enzyme showed no detectable activity, and product formation was confirmed by means of thin-layer chromatography and mass spectrometry. These findings establish CauSpe3 as a functional spermidine synthase. Full article

Bacteroides fragilis is a major commensal bacterium of the human colon. However, enterotoxigenic B. fragilis (ETBF) secretes B. fragilis toxin (BFT), a zinc-dependent metalloprotease that cleaves E-cadherin and promotes chronic inflammation and colorectal tumorigenesis. Despite extensive research, the cellular receptor for BFT remains unidentified. In this study, we developed His-tagged recombinant BFT variants including both catalytically active and inactive forms to facilitate biochemical and functional analyses. Functional assays confirmed that the active variant retained proteolytic activity and induced characteristic cellular responses, while the inactive variant served as an effective negative control. These results establish a robust experimental platform for BFT receptor identification and mechanistic studies of BFT-host interactions. The active and inactive BFT variants provide essential molecular tools for investigating ETBF pathogenicity and developing therapeutic interventions. Full article

Background: Ectopic fat deposition has been demonstrated to play a critical role in the onset and progression of renal dysfunction. However, research on renal parenchymal fat deposition and its association with renal dysfunction in type 2 diabetes mellitus (T2DM) remains limited, particularly regarding its association with early kidney injury. The present study aimed to further investigate the relationship between renal fat fraction (FF) and biomarkers of kidney injury, thereby providing new evidence for the potential link between intrarenal fat accumulation and early renal impairment in T2DM. Methods: This cross-sectional study enrolled 60 patients with T2DM. Renal FF was quantitatively assessed using magnetic resonance imaging (MRI). Clinical characteristics, body composition parameters, and biochemical indices were collected. Levels of kidney injury biomarkers, including tumor necrosis factor receptors 1 (TNF-R1), tumor necrosis factor receptors 2 (TNF-R2), chitinase-3-like protein 1 (YKL-40), and kidney injury molecule-1 (KIM-1), were measured using enzyme-linked immunosorbent assay (ELISA). To evaluate the correlations between fat distribution and inflammatory biomarkers, Pearson correlation analysis was performed. Furthermore, linear regression analysis was conducted to explore the associations between renal FF and kidney injury biomarkers with adjustments for potential confounders such as smoking status, diabetes duration, and visceral fat. Lasso regression was used to screen variables. Results: The results demonstrated that renal FF was significantly positively correlated with serum YKL-40 (r = 0.3, p = 0.021), TNF-R1 (r = 0.246, p = 0.042), and urinary KIM-1 (r = 0.396, p = 0.004), indicating a close association between renal fat accumulation and early kidney injury biomarkers. In regression analyses adjusted for age, sex, and duration of diabetes, the associations between renal FF and these biomarkers remained significant. After further adjustment for potential confounders, including smoking history, alcohol consumption, hypertension, renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, glucagon-Like Peptide-1 (GLP-1) receptor agonists, and lipid-lowering drugs, renal FF remained significantly associated with TNF-R1 (β = 0.327, p = 0.015), KIM-1 (β = 0.352, p = 0.021), and YKL-40 (β = 0.275, p = 0.025). Moreover, even after additional adjustment for visceral fat, the associations of renal FF with TNF-R1 and KIM-1 persisted. After using the Benjamini–Hochberg procedure for false discovery rate, the relationship between renal FF and KIM-1 had a significant difference. Variables of age and gender were excluded to build the parsimonious modeling using Lasso regression. It suggested that renal fat accumulation may contribute to kidney injury independently of visceral adiposity. Conclusions: The study systematically demonstrates a significant association between renal FF and early biomarkers of kidney injury in T2DM, which may suggest the potential role of renal fat accumulation in the pathogenesis of diabetic nephropathy. These findings provide clinical data support for the development of a fat-targeted intervention study. Future research should further elucidate the long-term mechanistic role of renal FF in diabetic nephropathy, as well as its potential value in early diagnosis and therapeutic applications. Full article

Thalassemia is a hereditary hemoglobinopathy characterized by ineffective erythropoiesis, chronic hemolysis, and transfusion-related iron overload, which collectively contribute to oxidative stress and organ dysfunction. The present study aimed to investigate the relationships between iron metabolism, oxidative stress biomarkers, and immune cell function across different clinical conditions. Peripheral blood samples were obtained from healthy individuals and patients with iron deficiency anemia, obesity, thalassemia trait (TT), β-thalassemia HbE (BTE), and β-thalassemia major (BTM). Hematological parameters were measured using automated hematology analyzers, while biochemical indicators, including liver enzymes and bilirubin, were determined using clinical chemistry assays. Iron overload was evaluated using serum iron parameters and T2*-weighted magnetic resonance imaging. Oxidative stress biomarkers, including reduced glutathione, thiobarbituric acid-reactive substances, and total antioxidant capacity, were assessed spectrophotometrically. Flow cytometric analysis was used to measure reactive oxygen species, redox-active iron, and lipid peroxide levels in granulocytes and lymphocytes. Thalassemia patients exhibited severe anemia, elevated liver enzymes, increased bilirubin levels, and significant alterations in iron metabolism compared with healthy controls. Hepatic iron accumulation was more common than cardiac iron deposition, particularly in BTE patients. Granulocyte oxidative burst activity was significantly reduced in thalassemia patients, whereas lymphocyte responses remained relatively preserved. Increased variability in glutathione levels suggested activation of intracellular antioxidant defense mechanisms in response to chronic oxidative stress. These findings highlight the complex interplay between iron overload, oxidative stress, and the immune cell dysfunction associated with thalassemia, thereby providing insights into improved monitoring and therapeutic strategies. Full article

Cannabinoids are high-value bioactive compounds whose sustainable production remains challenging, prompting interest in biocatalytic and microbial platforms as alternatives to plant extraction. In this study, we investigated the heterologous expression and functionality of two key cannabinoid-related enzymes in the photosynthetic microalga Chlamydomonas reinhardtii: the aromatic prenyltransferase, NphB_G286S/Y288A from Streptomyces sp., and the plant-derived cannabidiolic acid synthase (CBDAS) from Cannabis sativa. Codon-optimized genes were introduced into the nuclear genome of C. reinhardtii using several construct configurations and promoters, and stable transformants were generated and characterized for genomic integration, transcript accumulation, protein production, enzymatic activity, and cannabinoid-related metabolite formation. While NphB protein accumulation was achieved under the PSAD promoter control, CBDAS was not detected at the protein level under any condition tested. In vitro enzymatic assays using soluble algal protein extracts from NphB-expressing lines confirmed catalytic activity, yielding cannabigerolic acid (CBGA), reaching up to 633 ± 58 µg L⁻¹. However, no CBGA production was detected in vivo, despite substrate supplementation. These results indicate that, although bacterial prenyltransferase can be functionally expressed in C. reinhardtii, efficient metabolic conversion in vivo is limited by cellular and biochemical constraints, including substrate availability, intracellular compartmentalization, and potential competition with endogenous pathways. In contrast, the absence of detectable CBDAS highlights the challenges associated with expressing complex plant oxidocyclases in this photosynthetic host. Overall, this work provides mechanistic insights into enzyme compatibility and metabolic bottlenecks in microalgal systems and outlines key considerations for the future development of photosynthetic platforms for cannabinoid biocatalysis. Full article

Larix olgensis, a keystone timber species in Northeast China, is increasingly threatened by Neofusicoccum laricinum-induced shoot blight, a devastating disease that compromises forest health and necessitates sustainable management strategies. Here, we demonstrate that the endophytic bacterium Bacillus amyloliquefaciens JL54 elicits multifaceted defense responses in L. olgensis, enhancing resistance to pathogen infection. Greenhouse assays revealed that JL54 pretreatment reduced disease incidence by 12.5% and achieved 43.75% control efficacy while maintaining host vigor. Histochemical analyses identified JL54-induced rapid hydrogen peroxide (H₂O₂) accumulation, extensive lignin deposition, and localized programmed cell death (PCD), indicative of a primed immune response. Transcriptomic analyses uncovered distinct temporal defense patterns: early-stage responses (0 h post-inoculation) were characterized by upregulation of cutin, suberin, and wax biosynthesis pathways, reinforcing physical barriers, whereas late-stage responses (12 h post-inoculation) were dominated by ribosome- and proteostasis-related pathways (e.g., heat shock proteins [HSPs], glutathione S-transferases [GSTs]) to mitigate cellular damage. Biochemical assays corroborated these findings, with JL54 colonization reducing membrane lipid peroxidation (27.2% decrease in malondialdehyde content) and significantly elevating the activity of key defense enzymes, including peroxidase (POD), phenylalanine ammonia-lyase (PAL), and GST. Phytohormone profiling implicated jasmonic acid (JA) as the central mediator of induced systemic resistance (ISR), with JL54-potentiated JA signaling preceding pathogen containment. Collectively, these results demonstrate that JL54 contributes to a coordinated defense strategy in L. olgensis, integrating structural reinforcement (cuticle/lignin), oxidative stress management, and JA-mediated immune priming. These insights advance the understanding of endophyte-conferred resistance in conifers and highlight JL54’s potential as a biocontrol agent for sustainable forestry. Full article

Diet form is increasingly recognized as a welfare-relevant factor in intensive aquaculture, yet the effects of feed cooking on fish behavioral and physiological welfare remain poorly characterized. Juvenile southern catfish (Silurus meridionalis; 6.18 ± 0.52 g) were reared for 6 weeks in an indoor recirculating aquaculture system and fed either raw grass carp (Ctenopharyngodon idella) muscle (fish fed raw muscle, FR) or cooked grass carp muscle (fish fed cooked muscle, FC; 15 min ramp to ~100 °C followed by 2–3 min at ~100 °C). Locomotor activity and anxiety-like behavior were assessed using the open-field test and an annular light–dark preference assay, respectively. Flow-through respirometry further revealed a significantly lower standard metabolic rate (SMR) in FC fish than in FR fish, decreasing from 10.30 to 6.83, which represents a 33.7% reduction. Endocrine and biochemical analyses showed that cooking significantly decreased serum total triiodothyronine (T3) by 23.8%, whereas routine serum biochemical indices remained unchanged. In brain tissue, dopamine (DA) was significantly reduced by 7.2% in the FC group, and RT-qPCR analysis of dopamine-related genes further showed a significant downregulation of the rate-limiting synthesis gene th. These results indicate that cooking primarily downshifts the activity-energy axis in southern catfish and is accompanied by coordinated thyroid and dopaminergic changes. To our knowledge, this is the first integrated study to evaluate the behavioral, metabolic, and neuroendocrine effects of cooked feed in S. meridionalis, providing a short-term phenotypic baseline for assessing welfare-relevant feeding scenarios in aquaculture. Full article

Streptococcus parauberis is a major pathogen responsible for streptococcosis in both marine and freshwater fish species, causing substantial economic losses in aquaculture. The increasing prevalence of multidrug resistance has highlighted the urgent need for alternative disease control strategies. Interference with bacterial quorum sensing (QS) systems represents a promising approach. This study aimed to identify and biochemically characterize an Rgg-family transcriptional regulator and evaluate its potential as a target for quorum sensing-related regulatory interference in vitro. We hypothesized that this Rgg regulator may function as a quorum sensing-associated transcription factor capable of promoter binding and modulation by small molecules. Bioinformatic analyses were used to identify the rgg gene encoding an Rgg-family transcriptional regulator and predict its structural features. The gene was cloned, heterologously expressed, and purified. Promoter binding activity was examined using electrophoretic mobility shift assay (EMSA), and key amino acid residues were identified through site-directed mutagenesis. The inhibitory effect of the cyclic peptide cyclosporin A (CsA) on Rgg-promoter binding was further assessed. The rgg gene (864 bp) encoding a 287-amino-acid protein (34.1 kDa) was successfully identified and expressed. Purified Rgg specifically bound to its own promoter region in a concentration-dependent manner. Mutations at conserved arginine residues R12 and R15 within the helix-turn-helix DNA-binding domain abolished promoter binding activity. Furthermore, CsA disturbed Rgg-promoter binding in a dose-dependent manner. This study provides the first in vitro characterization of an Rgg-family transcriptional regulator in fish-derived S. parauberis. The findings expand current understanding of Rgg-family regulators potentially associated with quorum sensing in aquatic streptococci and provide a preliminary basis for further investigation of quorum sensing-related regulatory interference strategies for controlling streptococcal diseases in aquaculture. Full article

To address the challenge of depleting traditional feed resources, this study aimed to biovalorize sweet potato waste (SPW), a major byproduct of the Japanese shochu industry, into a high-value functional animal feed. An innovative two-stage solid-state fermentation (SSF) was employed, featuring an initial aerobic stage with Aspergillus oryzae for substrate degradation, followed by an anaerobic stage with Lactobacillus plantarum for nutritional enhancement. To optimize this complex, multi-variable process, the predictive performance of Artificial Neural Network (ANN) and Random Forest (RF) machine learning models was compared based on an augmented experimental dataset (N = 80). To ensure statistical robustness and prevent data leakage, a repeated k-fold cross-validation strategy was implemented. The RF model demonstrated significantly superior accuracy and reliability than the ANN model, particularly in predicting the primary metric, crude protein (R² = 0.61 ± 0.04 vs. R² = 0.12 ± 0.15). Subsequently, the validated RF model was integrated with a Constrained Differential Evolution (CDE) algorithm for global parameter optimization. The optimized process was predicted to yield a final product with a crude protein content of 25.0%, alongside significant increases of 114.1% in total amino acids and 123.9% in essential amino acids. These projections were experimentally validated in vitro, confirming the model’s accuracy with a relative error of less than 5%. Furthermore, comprehensive biochemical assays demonstrated a massive degradation of anti-nutritional factors and significant enhancements in total phenolic content and antioxidant activity. This study provides a scientifically validated, data-driven framework for the valorization of SPW. It confirms the superior efficacy of ensemble learning methods for optimizing complex bioprocesses with limited data, offering a contribution to the development of a circular bioeconomy and sustainable feed resources. Full article

Rapid population growth is intensifying global energy demand and waste generation. Slaughterhouse waste is creating important environmental problems. Transforming this into renewable energy through technologies like anaerobic digestion offers a sustainable pathway to reduce environmental impacts and support the energy transition. The main objective of this study was to examine the biodegradability of the slaughterhouse semi-liquid fraction (S), slaughterhouse liquid fractions (L), and their mixtures (25%, 50%, and 75%) through a two-phase anaerobic co-digestion (TPAcD) process. Batch reactors were operated in two separate microbiological and thermal phases. In the first, a thermophilic 55 °C–acidogenic stage, biochemical hydrogen potential (BHP) assays were conducted to evaluate green hydrogen production, while in the second, a mesophilic 35 °C–methanogenic stage, biochemical methane potential (BMP) assays were carried out to assess biomethane generation. The most relevant findings revealed that while liquid fractions maximized hydrogen recovery, overall yields remained limited due to competitive metabolic pathways. Notably, the 25L:75S configuration optimized hydrolysis, with a 1280% increase in soluble COD, establishing the semi-liquid fraction as a critical organic reservoir for thermophilic–acidogenic activity. In the subsequent stage, the acidogenic pre-treatment significantly enhanced methanogenesis, where the same 25L:75S mixture exhibited a synergistic methane yield of 495.46 mL CH₄/g VS. This 13.8% improvement over the theoretical additive potential confirms that strategic substrate balancing overcomes individual feedstock limitations, maximizing energy recovery in sequential anaerobic digestion. These results highlight the potential of phase-separated anaerobic co-digestion as a strategy to improve the valorization of slaughterhouse wastes. Full article

The increasing demand for different value-added products from natural seaweeds requires a sustainable cultivation method for the regular supply of biomass and to safeguard the natural ecosystem from overexploitation. This study evaluated laboratory acclimatization of the green seaweed Acrosiphonia orientalis (DGR: 2.71 ± 0.21%; GPP: 12.55 ± 0.1 mg O₂ L⁻¹ day⁻¹), followed by a comparative evaluation of its physicochemical and biochemical characteristics, metabolite profile, and antiproliferative activity compared with naturally harvested seaweed. Metabolite profiling identified 47 compounds exhibiting differential accumulation patterns, with the natural specimens enriched in omega-3 polyunsaturated fatty acids, including docosahexaenoic acid, and the laboratory-acclimatized specimens exhibited elevated arachidonic acid levels. Amino acid profiling revealed higher concentrations of essential and non-essential amino acids in the natural specimens, with prominent levels of phenylalanine and aspartic acid, while the lab-acclimatized specimens were enriched in isoleucine, methionine, proline, and cysteine. The lab-acclimatized specimens exhibited significantly enhanced water absorption (WSC: 6 ± 0.25 mL/g DW; WHC: 2.68 ± 0.11 g/g DW) and higher total sugar (47.11 ± 0.52% Glc eq. DW) and phenolic contents (51.28 ± 0.54 mg GAE g⁻¹ extract), while the natural specimens had a superior oil-holding capacity (OHC: 1.8 ± 0.12 g/g DW); higher total flavonoid (123.62 ± 2.97 mg Q g⁻¹ extract), protein (5.11 ± 0.36 µg BSA eq/mg DW), and chlorophyll contents (8.82 ± 0.58 mg/L); and higher antioxidant activities (ABTS-EC₅₀: 67.33 ± 0.97 μg/mL extract). The mineral analysis revealed distinct elemental profiles, with enrichment of sodium, magnesium, and calcium in the lab-acclimatized specimens and a more favorable Na/K ratio (0.14 vs. 0.78) in the natural specimens. Of note, extracts from both seaweeds exhibited significant dose-dependent antiproliferative activity against HeLa cervical cancer cells (Wild EC₅₀: 118.63 ± 14.14 µg/mL extract; lab EC₅₀: 153.35 ± 10.18 µg/mL extract), suppressed colony formation in soft agar assays, induced nuclear condensation (based on Hoechst staining), and modulated the expression of key oncogenes (upregulating NDRG1, TP53, and CASP3 and downregulating BCL2, MYC, and CCND1). Collectively, this study provides an approach to acclimatize A. orientalis that may be utilized for developing a cultivation method. Moreover, this green seaweed has a great potential to be used for nutraceutical and functional food applications. Full article

Mycoplasma pneumoniae is a significant pathogen responsible for community-acquired respiratory infections in children and adolescents, with the rising prevalence of macrolide-resistant M. pneumoniae (MRMP), particularly in Asia, presenting critical treatment challenges. Our previous study inferred that a macrolide efflux pump may contribute to macrolide resistance in M. pneumoniae in addition to the common point mutations in 23S rRNA gene. This study aimed to define the specific pump and confirm its role. Through comparative genomic analysis, we identified a candidate gene, MPN_080, encoding an ABC transporter permease, which was further characterized using phylogenetic analysis, AlphaFold-based structural modeling, and biochemical assays. Overexpression of MPN_080 from an erythromycin-resistant isolate in the erythromycin-sensitive M129 resulted in a significant increase in minimum inhibitory concentrations (MICs) from <0.125 µg/mL to 1 µg/mL, while similar overexpression of MPN_080 derived from M129 did not affect MICs. Notably, this resistance mechanism operates independently of M. pneumoniae virulence factors, as evidenced by unaltered colonization capacity in NCI-H292 cells and consistent immune response patterns across both strains. Our findings establish MPN_080 as a novel determinant of macrolide resistance functioning associated with enhanced ATPase activity. These insights into non-classical resistance mechanisms may guide future diagnostic and therapeutic strategies against MRMP. Full article