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Effects of apple phenolics on the human metabolome: modulation of key metabolic pathways.

Apples are widely recognized for their potential health benefits, partly attributed to their phenolic compounds. However, their impact on human metabolism remains incompletely understood. This study investigated metabolic effects of apple-derived phenolic compounds using untargeted metabolomics approach across multiple biofluids. In a crossover intervention study, 30 healthy men consumed a phenolic-rich apple juice or a placebo for two weeks. Blood, urine and saliva samples were collected before and after each intervention and analyzed by direct infusion ultra-high resolution mass spectrometry. Consumption of apple phenolic compounds resulted in significant alterations of the human metabolome, including increased levels of phenolic-derived degradation products and microbial-associated metabolites across all biofluids. Pathway enrichment analysis revealed pronounced effects on phenylalanine and tyrosine metabolism, as well as linoleic and arachidonic acid metabolism, Overall, these findings demonstrate that apple phenolic compounds induce measurable, microbiota-associated and systemic metabolic changes, providing new insights into their metabolic fate and biological relevance.

Humans

LitCTL1: A novel C-type lectin involved in the mucosal and cellular immunity of the common periwinkle Littorinalittorea.

C-type lectins (CTLs) are vital pattern-recognition receptors (PRRs) that mediate innate immune responses in mollusks, yet their characterization in Caenogastropoda, the largest gastropod group, remains limited. This study characterizes LitCTL1, a novel secreted single-domain C-type lectin from the common periwinkle, Littorina littorea. The 199-amino acid polypeptide contains a conserved carbohydrate recognition domain with canonical QPD and WND motifs and is predicted to form a homodimer. Uniquely, LitCTL1 was localized in both circulating hemocytes and mucus-secreting epithelial cells of the foot, mantle, and hypobranchial gland - the first report of such dual localization for a molluscan lectin, linking systemic and mucosal defense. Expression analysis revealed that LitCTL1 is constitutively expressed in hemocytes. Functional assays with recombinant LitCTL1 demonstrated its role as a potent opsonin with hemagglutinating activity, significantly enhancing hemocyte spreading and the phagocytosis of zymosan. Genomic analysis reveals that LitCTL1 belongs to a rapidly diversifying, genus-specific expansion distinct from conserved perlucin-like lineages. These results identify LitCTL1 as a key effector molecule in both systemic and mucosal innate immunity, likely reflecting an evolutionary adaptation to the microbial challenges of the intertidal environment.

Animals

Ramu stunt virus genome reveals previously unreported segments and nucleocapsid domain duplication in Mechlorovirus.

Ramu stunt virus (RmSV), a member of the genus Mechlorovirus within the family Phenuiviridae, was previously described as a six-segmented RNA virus infecting sugarcane. In this study, we re-examined type material and additional isolates using high-throughput sequencing and RT-PCR validation, revealing that RmSV possesses a nine-segmented genome, making it the largest reported in the Phenuiviridae. This expanded architecture includes duplicated RNA segments (RNA 2a and RNA 2b) encoding nucleocapsid-like proteins and two novel segments (RNA 7 and RNA 8). Comparative analysis showed that RNA 2a and 2b share about 84% amino acid identity, while RNA 5 encodes a third nucleocapsid homolog, indicating unprecedented domain redundancy. Structural modeling confirmed that all three nucleocapsid proteins maintain a conserved fold despite low sequence identity, with electrostatic mapping suggesting differential RNA-binding potential. Additionally, RNA 6 encodes a hypothetical protein structurally similar to the rice stripe virus disease-specific S-protein, implicating a role in symptom development. Transcript abundance analysis revealed RNA 6 as the most highly expressed segment across isolates. These findings revise the genomic composition of RmSV, highlight mechanisms of genome plasticity and adaptive evolution in plant-infecting bunyaviruses, and underscore practical implications for diagnostic assay design, resistance breeding, and biosecurity surveillance.

Genome, Viral

Molecular mechanisms of neuroendocrine regulation of molting in the Chinese mitten crab (Eriocheir sinensis): A transcriptomic analysis based on eyestalk ablation model.

Molting disability severely restricts the sustainable aquaculture of the Chinese mitten crab, yet the neuroendocrine mechanisms coordinating physiological responses remain poorly understood. Using unilateral eyestalk ablation to remove the primary source of molt-inhibiting hormone (MIH), we performed time-resolved transcriptomic profiling of the thoracic ganglion at 24 h (early premolt) and 48 h (ecdysis) post-ablation. We identified 2825 differentially expressed genes and uncovered a biphasic molecular response. At 24 h, the thoracic ganglion activates pathways associated with neuromuscular adaptation, oxidative stress, and cardiac muscle contraction. Notably, the arachidonic acid metabolism pathway is selectively rewired: cytochrome P450 ω-hydroxylases (CYP2J2, CYP4V2) are upregulated, while competing branches (epoxide hydrolase, cyclooxygenase) are suppressed, promoting local synthesis of the potent vasoconstrictor 20-HETE within the thoracic ganglion. This enzymatic switch provides a mechanistic link between MIH withdrawal and the local generation of elevated hemolymph pressure required for molting. By 48 h, the transcriptional program shifts toward chitin-based extracellular matrix remodeling, glycosphingolipid biosynthesis, and synaptic reorganization. Collectively, our findings redefine the thoracic ganglion as an active neuroendocrine integrator that translates reduced MIH signaling into phased physiological outputs, revealing a "neuro-endocrine-hemolymph pressure" regulatory axis. This study provides novel molecular targets (e.g., CYP2J2, CHS1, UGCG) for mitigating molting disability in E. sinensis aquaculture.

Animals

Discovery and characterization of multifunctional bioactive peptides from Alaska Pollock (Gadus chalcogrammus) milt: hybrid in silico, in vitro, and proteomic approaches.

The growing demand for multifunctional bioactive peptides has sparked interest in underutilized marine by-products as sustainable bioresources. This study explored Alaska Pollock (Gadus chalcogrammus) milt protein as a novel source of peptides with anti-inflammatory, anti-hypertensive, and anti-diabetic effects. Protein composition was analyzed via LC-MS, followed by in silico digestion and bioactivity prediction. Molecular docking identified peptides targeting DPP-IV, α-glucosidase, ACE, GLP-1 receptor, COX-2, MuRF1, and the 20S proteasome. Among the candidates, a promising peptide (CLPPH) was synthesized and validated in vitro, demonstrating inhibitory effects on nitric oxide production, DPP-IV, ACE, and α-glucosidase. These results highlight CLPPH's potential as a multifunctional bioactive peptide and support the valorization of Alaska Pollock milt as a sustainable source for functional foods and nutraceutical applications.

Animals

The RrWRKY75-mediated activation of ascorbate synthesis in Rosa roxburghii Tratt contributes to salt stress tolerance.

L-Ascorbic acid (AsA) is a key antioxidant that alleviates oxidative stress in plants. Previous yeast one-hybrid (Y1H) screening identified RrWRKY75 as a transcription factor capable of binding to the promoter of RrGGP2 (GDP-L-galactose pyrophosphatase 2), a key structural gene responsible for massive AsA accumulation in Rosa roxburghii fruit. The function of RrWRKY75 in plant stress responses remains unclear. Here, RrWRKY75 is verified to specifically bind to the RrGGP2 promoter and activate its transcription. This positive regulatory effect on RrGGP2 transcript levels and AsA accumulation is further confirmed through overexpression or silencing of RrWRKY75 in R. roxburghii fruit or callus. Among various abiotic stress conditions, RrWRKY75 expression is significantly induced by salt stress. Upon its overexpression in callus or Arabidopsis thaliana, elevated AsA levels and antioxidant capacity are observed, thereby enhancing salt tolerance. Interestingly, RrWRKY75 also binds to the promoter of RrUNE12, a salt-responsive factor in R. roxburghii, and activates its expression. Moreover, yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assays confirm the physical interaction between RrWRKY75 and RrUNE12, which jointly upregulates RrGGP2 expression and AsA production. Collectively, RrWRKY75 boosts AsA biosynthesis and salt tolerance both by directly trans-activating RrGGP2 and by synergizing with RrUNE12 through transcriptional activation and protein complex formation. These findings provide insights into the regulatory role of RrWRKY75 in abiotic stress tolerance and offer valuable genetic resources for R. roxburghii germplasm improvement.

Rosa

Early proteomic and metabolic signatures of liver and eye in OAT-deficient mice.

Ornithine aminotransferase (OAT) deficiency causes hyperornithinemia and gyrate atrophy (GA) of the choroid and retina, a rare inherited retinal degeneration. To understand the early molecular changes that make the eye susceptible to damage, we performed quantitative proteomic and metabolomic profiling of liver, retina, and retinal pigment epithelium and choroid (RPE/Cho) from OAT-deficient (Oatrhg) mice prior to detectable vision impairment. In addition to reduced OAT expression and elevated ornithine, methylation-related metabolites such as N(6)-methyl-lysine were altered in all examined tissues of Oatrhg mice. In the liver, excess ornithine was directed into urea cycle metabolism, together with altered expression of detoxification enzymes and histone H2B proteins. In contrast, the retina showed minimal proteomic changes but pronounced alterations in amino acid pathways that support glutamate homeostasis. The RPE/Cho demonstrated the most extensive proteomic changes, particularly in mitochondrial metabolism, cytoskeleton, and extracellular matrix, along with changes in metabolites involved in lysine metabolism, energy metabolism, and antioxidant capacity. Incubation with 13C lysine demonstrated that lysine was primarily degraded in RPE/Cho but not the retina, and ornithine enhanced lysine degradation in an OAT-dependent manner. Together, these findings highlight common and tissue-specific impacts of OAT on the liver and ocular tissues and provide insight into early molecular changes that contribute to the selective vulnerability of the eye in GA. Proteomics data are available via ProteomeXchange (PXD063614) and metabolomics data via MassIVE repository (MSV000101103).

Animals

Spatially confined electrochemical strategy with DNA-assembled nanogaps for SNP detection.

Accurate detection of low-abundance single nucleotide polymorphisms (SNPs) against a large excess of homologous wild-type sequences requires both selective molecular recognition and effective transduction of small sequence differences into measurable signals. Here, we report a spatially confined electrochemical strategy that couples sequence-selective recognition with size-dependent mass-transport gating. DNA-hybridization-driven self-assembly of gold nanoparticles (AuNPs) forms a three-dimensional self-assembled electrode (3D-SAE) with a DNA-defined interparticle architecture. Competitive probes (SP/WP) convert single-base recognition into distinct molecular-size states: the SNP-associated pathway preferentially triggers a hybridization chain reaction (HCR), generating bulky AuNP-anchored HCR/methylene blue complexes (Au@HCR/MB) with reduced electrochemical accessibility through the porous 3D-SAE, whereas the wild-type pathway does not trigger HCR and maintains a high-current response from more readily accessible MB-containing species. Thus, sequence recognition is translated into a molecular-size difference and subsequently into an electrochemical signal through differential mass transport. Under buffer conditions, the platform achieved a statistically estimated detection limit of ∼0.47 fM and a quantitative range of 1 fM-100 pM. It discriminated a 0.1% mutant abundance in a fragmented genomic-DNA background. The downstream signal-transduction chemistry is enzyme-free and isothermal. This work establishes a mechanistical recognition-size-conversion-mass-transport-gating architecture for electrochemical nucleic acid analysis.

Polymorphism, Single Nucleotide

Distinct cell morphotypes of Aureobasidium melanogenum ZN exhibit differential functional profiles in promoting maize growth.

Black yeast-like fungi of the genus Aureobasidium exhibit morphological plasticity, but whether distinct cellular states within the same genetic background are associated with different plant growth-promoting functions remains unclear. Here, yeast-like cells (YL), swollen cells (SC), and chlamydospores (CH) of Aureobasidium melanogenum ZN were characterized. YL was associated mainly with siderophore production and laccase activity, SC with extracellular polysaccharide accumulation, and CH with phosphate mobilization and higher ammonia and IAA production. Whole-genome and comparative genomic analyses revealed a shared repertoire related to nutrient acquisition, auxin-associated metabolism, extracellular oxidation, and carbohydrate remodeling, with expansions in nutrient- and cell-surface-related gene families. Transcriptomic and metabolomic analyses showed distinct deployment of these capacities, with CH exhibiting broad reprogramming of tryptophan-associated, nitrogen, phosphate, central-carbon, and amino-acid metabolism. In maize, CH at the optimal inoculation concentration of 105 CFU·mL-1 produced the strongest growth promotion, increasing plant height, dry biomass, root length, root surface area, and root volume by 58.6%, 365.1%, 191.0%, 194.3%, and 222.4%, respectively. Consistent with this pronounced growth phenotype, maize root transcriptomics showed coordinated CH-induced responses involving root development, nutrient transport, redox regulation, and root-interface remodeling. Root-zone tracking showed greater short-term stability and persistence of CH. These findings identify cellular state as an important functional dimension of Aureobasidium-plant interactions and provide a basis for developing fungal inoculants with defined beneficial cellular states.

Zea mays

Associations of clinical and laboratory parameters with pediatric urolithiasis composition: A retrospective, single-center study.

OBJECTIVE: To investigate demographic, clinical, and laboratory factors associated with distinct stone compositions in children. METHODS: This retrospective study included 237 children aged <14 years who underwent stone composition analysis between July 2008 and November 2023. Demographic, clinical, and laboratory data were collected, and propensity score matching (PSM) was used to control for confounding factors. RESULTS: The urate component (uric acid anhydrous, ammonium acid urate, and sodium urate) was most prevalent in infants, males, and non-Han children, whereas the calcium oxalate component predominated in older children. Analysis of coexisting components revealed urate is the most common partner to calcium oxalate (67.6%), and vice versa (82.8%). Struvite most frequently coexisted with carbonate apatite (60%), while carbonate apatite most often coexisted with calcium oxalate (54%). After PSM, the urate component was independently associated with host metabolic dysregulation, including lower high-density lipoprotein (&#x3b2; = -0.175, 95% CI: -0.279 to -0.071, p = 0.001) and with coagulation dysfunction, as evidenced by a prolonged prothrombin time (&#x3b2; = 0.595, 95% CI: 0.125 to 1.064, p = 0.014). Additionally, preoperative urinary tract infection (UTI) and congenital urinary tract anomalies were independently associated with both carbonate apatite and struvite components, with directionally consistent but quantitatively unstable signals in the struvite cohort, whereas the calcium oxalate component exhibited an inverse association with UTI (OR = 0.156, 95% CI: 0.030 to 0.819, p = 0.028). Furthermore, the carbonate apatite component was also independently associated with an elevated systemic immune-inflammation index (&#x3b2; = 416.53, 95% CI: 60.05 to 773.01, p = 0.024) and systemic inflammation response index (&#x3b2; = 1.286, 95% CI: 0.086 to 2.487, p = 0.038). CONCLUSION: Urate component was prevalent in infants, males, and non-Han children, whereas calcium oxalate predominated in older children. After adjusting for confounders, urate composition was associated with metabolic abnormalities, the carbonate apatite component was linked to infection and anatomical malformations, and a similar directional pattern was observed in the struvite cohort.

Humans

Strategy for enhanced production of A40926B0 in Nonomuraea gerenzanensis using an efficient CRISPR/AsCas12f1 system.

The global emergence of vancomycin-resistant Gram-positive pathogens underscores the urgent need for efficient production of novel lipoglycopeptide antibiotics. Dalbavancin, a last-resort therapeutic agent, relies on its key biosynthetic precursor A40926B0, whose industrial manufacture is severely limited by the low yield of wild-type Nonomuraea gerenzanensis and inefficient genetic tools for this rare actinomycete. Here, we developed a high-efficiency CRISPR/AsCas12f1 genome editing system and applied systematic metabolic engineering to boost A40926B0 biosynthesis. First, conjugation conditions were optimized to elevate the transfer efficiency in N. gerenzanensis D11. The hypercompact AsCas12f1 nuclease showed markedly lower cytotoxicity than SpCas9 and enabled 100% gene deletion efficiency with preferred PAMs (TTTG, CTTG, GTTG). Second, we strengthened the shikimate pathway via multiple genetic strategies: overexpressing feedback-resistant DAHP synthase (aroG fbr ) and chorismate mutase/prephenate dehydrogenase (tyrA fbr ), as well as knocking out pheA. This manipulation blocks the phenylalanine synthetic branch and redirects metabolic flux toward the l-tyrosine branch. Third, we engineered the branched-chain fatty acid (BCFA) pathway via promoter replacement of bkdA2B2C2, LipAB, fabF and deletion of acdH to enhance isododecanoyl side-chain supply. The combinatorial engineering yielded strain B-13, which produced 1740&#x202f;mg/L A40926B0 in shake flasks. Finally, 50-L fed-batch fermentation with continuous maltodextrin feeding further increased the titer to 1817&#x202f;mg/L, the highest reported titer to date. This work establishes a robust CRISPR editing tool for N. gerenzanensis and provides valuable engineering references for precursor-oriented strain improvement targeting lipoglycopeptide antibiotics, offering insights for the industrial scale production of A40926B0.

A40926B0

Effects of six weeks of guanidinoacetic acid supplementation with and without creatine monohydrate on cognitive function and markers of health in healthy adults.

BACKGROUND: Guanidinoacetic acid (GAA) supplementation has been reported to increase brain creatine content more effectively than creatine monohydrate (CrM). However, the effects on cognitive function are unclear. PURPOSE: The purpose of this proof-of-concept exploratory clinical trial was to determine whether GAA supplementation with and without CrM affects cognitive function and/or markers of health. METHODS: In a double-blind, randomized, and counterbalanced manner, 58 healthy and active adults (33 females, 35.5&#x2009;&#xb1;&#x2009;14 years, 76.2&#x2009;&#xb1;&#x2009;14 kg) ingested a PLA (PLA, 2 &#xd7; 6 g/d maltodextrin), GAA (2 &#xd7; 1 g/d)&#x2009;+&#x2009;PLA (2 &#xd7; 5 g/d), or GAA (2 &#xd7; 1 g/d)&#x2009;+&#x2009;CrM (2 &#xd7; 5 g/d) for six weeks. The participants donated fasting blood samples and completed a battery of tests and questionnaires assessing various aspects of function, mood, stress, sleep quality, and markers of health at baseline and after six weeks of supplementation. Data were analyzed using General Linear Model (GLM) multivariate and univariate with repeated measures, and mean changes from baseline with 95% confidence intervals, and Chi-squared analysis, and considered significant when the probability of error was 0.05 or less, and approaching significance (p&#x2009;>&#x2009;0.05-p&#x2009;<&#x2009;0.10). RESULTS: GAA supplementation tended to improve overall reaction time (-241.8&#x2009;ms [-533, 50], p&#x2009;=&#x2009;0.10) while significant interaction effects were observed in overall reaction time (p&#x2009;=&#x2009;0.031-330 ms [-629, -31]) and YES reaction time (-290&#x2009;ms [-484, -96], p&#x2009;=&#x2009;0.004) while recalled correct reaction time (-178&#x2009;ms [-374, 21], p&#x2009;=&#x2009;0.078) and recalled correct YES (7.4 % [-1, 15.8], p&#x2009;=&#x2009;0.084) approached significance compared to PLA. Limited to no effects were observed on the Delayed Picture Recognition Task Test, Digit Vigilance Task Test, Corsi Block Task Test, or Stroop Color-Word Task Test. The amount of time engaged in moderate physical activity was significantly greater (p&#x2009;<&#x2009;0.05) in the GAA group compared to PLA. Participants in the GAA group reported a lower frequency of controlling irritations (p&#x2009;=&#x2009;0.036), and feeling like difficulties are mounting (p&#x2009;=&#x2009;0.053) on the Perceived Stress Scale. Some positive and potentially undesirable effects were observed in sleep quality assessments. The quality of life assessment revealed that participants in the GAA group reported less frequent feelings of being worn out (p&#x2009;=&#x2009;0.068) and that their health was excellent (p&#x2009;=&#x2009;0.092) while those in the GAA&#x2009;+&#x2009;CrM group reported more frequent limitations when bending, kneeling, or stooping (p&#x2009;=&#x2009;0.053), more often feeling full of life (p&#x2009;=&#x2009;0.081), and less frequency in feeling downhearted and depressed (p&#x2009;=&#x2009;0.066). No clinically meaningful changes were observed in blood markers or self-reported side effects among the groups. CONCLUSION: Dietary supplementation with GAA (2 g/d) and the combination of CrM (10 g/d&#x2009;+&#x2009;GAA 2 g/d) for six weeks improved delayed verbal episodic recognition memory and retrieval speed and some measures of perceived stress, sleep quality, and quality of life. However, most cognitive tests were not affected, particularly when comparing the GAA to the PLA group; there were some inconsistencies in the findings, and several differences only approached significance. Additional research is needed before conclusions can be drawn. Clinical trial registration: ISRCTN68542582.

Humans

PdIr bimetallic nanozyme engineered metal-organic frameworks integrated dual-mode sensor toward Stx2 detection in food.

Shiga toxin II (Stx2) has attracted extensive attention due to its toxicity and pathogenicity, making the development of sensitive detection methods urgent. This study constructed a dual-mode sensing platform for the sensitive detection of Stx2 in food. Composite material UIO-66@PdIr with peroxidase-like activity and fluorescent properties was synthesized and combined with cDNA as the signal probe, while aptamer-modified magnetic beads served as the capture probe. Specific binding of Stx2 to the aptamer triggered the release of the signal probe, enabling colorimetric and fluorescence signal readout. The colorimetric mode showed a linear range of 0.05-100&#xa0;ng/mL with an LOD of 0.039&#xa0;ng/mL, and the fluorescence mode exhibited 0.01-1000&#xa0;ng/mL with an LOD of 0.0097&#xa0;ng/mL. Additionally, this method was successfully applied to the detection of Stx2 in food, and the recovery rates were 94.33%&#xa0;&#x223c;&#xa0;102.20%. It indicated that the constructed sensor holds great practical potential for Stx2 detection.

Food Contamination

Molecular adaptation of caspase genes to salinity stress in the tropical sea cucumber Stichopus monotuberculatus: A comparative analysis across echinoderms.

Apoptosis is an essential physiological process that plays a critical role in development and tissue homeostasis. Caspases, as central regulators of apoptosis, are crucial in controlling inflammation and cell death. In this study, we investigated the caspase gene family in Stichopus monotuberculatus to explore their potential roles in salinity stress adaptation. Five caspase genes were identified from the genome of S. monotuberculatus, including Smcaspase3, Smcaspase6, Smcaspase8a, Smcaspase8b, and Smcaspase8c. Phylogenetic analysis revealed that these Smcaspase genes clustered into distinct caspase subfamilies and showed high conservation with homologs from other echinoderms and representative vertebrates. Conserved motif and gene structure analyses showed relatively similar structural patterns within each clade, whereas divergence was observed among different subfamilies. Promoter analysis identified numerous cis-acting elements related to gene regulation, immune response, and growth and development. Expression profiling under salinity stress showed that Smcaspase8a was significantly upregulated, particularly under prolonged stress, whereas the other genes exhibited limited transcriptional responses. Our findings highlight caspase function in salinity stress and provide the foundation of molecular salinity adaptation mechanisms in S. monotuberculatus.

Animals

Specialized pro-resolving mediators in obesity and overweight conditions: A systematic review of human and animal evidence on comparative differences and associations.

Obesity and overweight are characterized by persistent low-grade inflammation. Specialized pro-resolving mediators (SPMs), polyunsaturated fatty acid-derived metabolites, actively promote inflammatory resolution, and their dysregulation has been linked to unresolved inflammation and metabolic disturbances in obesity. This systematic review synthesized human and animal evidence on adiposity-related differences and associations in SPMs and SPM precursors. The protocol was prospectively registered in PROSPERO (CRD420251067464). PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched up to 22 May 2026. Eligible studies included human and animal research comparing SPMs and/or SPM precursors between overweight/obese and normal-weight/lean groups or assessing their associations with adiposity indices. Due to heterogeneity across matrices and analytical platforms, findings were synthesized narratively. Twenty-seven unique studies were included, providing 28 experimental datasets (14 animal and 14 human). The most consistent alterations were observed in adipose tissue and circulation, where overweight/obesity was frequently associated with lower concentrations of SPMs and/or SPM precursors. In humans, circulating Resolvin E1 showed reproducible reductions and was inversely associated with adiposity measures in several cohorts. In contrast, selected metabolites, including SPM Lipoxin A4 and the SPM precursors 15-HETE and 18-HEPE, exhibited mixed directionality across studies. Evidence for hepatic and central nervous system compartments was limited and heterogeneous. Overall, available evidence suggests that excess adiposity is associated with altered SPM and precursor profiles, most consistently in adipose tissue and circulation, whereas hepatic and central nervous system findings remain inconsistent. Future studies using standardized quantification and tissue-specific designs are needed to clarify whether targeting pro-resolving pathways has translational potential in obesity-related metabolic dysfunction.

Animals

A horizontally acquired gene mediates insect cocoon pigmentation in the eri silkmoth, Samia ricini.

Holometabolous insects make cocoons during larval-pupal metamorphosis to protect the pupal phase. The materials used for cocoon construction vary widely. Lepidopteran insects typically secrete silk to form cocoons, which display diverse colors. The eri silkworm, Samia cynthia ricini, is an economically important domesticated species that mostly produces white cocoons, with some varieties producing red cocoons. The enzyme kynureninase (KYNU), acquired from bacteria by horizontal gene transfer, has previously been implicated in insect coloration, while the tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) has been identified as a red pigment. However, exactly how KYNU is involved in cocoon pigmentation remains unclear. Here, we report that a horizontally transferred bacterial gene encoding KYNU regulates red cocoon formation. Metabolomic analysis revealed a high accumulation of 3-HAA in red cocoons, confirming its role as the primary pigment and associating the coloration with tryptophan metabolism. Quantitative real-time polymerase chain reaction (qPCR) analysis indicated that SrKYNU is highly expressed in the silk glands and significantly downregulated in the red cocoon strain compared to the white cocoon strain. Genomic sequencing identified a 141 bp deletion in the upstream regulatory region of KYNU in the red cocoon strain compared to the white cocoon strain. Dual-luciferase assays confirmed that this deletion significantly reduced promoter activity. CRISPR/Cas9 knockout of SrKYNU in the white-cocoon strain resulted in mutants producing red cocoons with elevated 3-HAA content. These findings reveal that the horizontally transferred gene SrKYNU exhibits tissue-specific expression and regulates cocoon coloration in S. ricini, illustrating that horizontal gene transfer can play an important role in regulating an insect physiological process.

Animals

Risk prediction models for blood transfusion in patients undergoing total hip and knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and evaluate published risk prediction models for perioperative blood transfusion in patients undergoing total hip or knee arthroplasty (THA/TKA). METHODS: We systematically searched PubMed, Web of Science, the Cochrane Library, and Embase from inception to May 31, 2025. Two researchers independently screened the literature, extracted data, and assessed the risk of bias and applicability using the Prediction model Risk Of Bias Assessment Tool (PROBAST). The area under the receiver operating characteristic curve (AUC) values were pooled via a meta-analysis using Stata 18.0. RESULTS: d Fourteen studies containing 36 prediction models were included. The incidence of blood transfusion among THA/TKA patients ranged from 3.2% to 30.8%. Preoperative hemoglobin (Hb) level, tranexamic acid (TXA) use, operative duration, intraoperative blood loss, and age were the most frequently incorporated predictors. Model sensitivity ranged from 58% to 94.5%, and specificity ranged from 71.3% to 94%. Meta-analysis showed that the pooled AUC value of the 13 validated models was 0.87 (95% CI: 0.85-0.90), suggesting good discriminatory performance. All models were rated as having a high risk of bias. The applicability of four studies was rated as unclear. CONCLUSION: Although the included studies demonstrated promising discriminative ability of prediction models for blood transfusion in THA/TKA, all were assessed as having a high risk of bias using the PROBAST tool. Therefore, future research should prioritize the development of models with larger sample sizes, rigorous study designs, and multicenter external validation.

Humans

Ecotoxicological responses of aquatic macrophytes to 2,4-D: A global synthesis of species sensitivity and ecological risk.

The widespread use of 2,4-dichlorophenoxyacetic acid (2,4-D) has raised concern about its persistence, mobility, and effects on non-target aquatic vegetation in freshwater ecosystems. Here, we provide a global synthesis of the ecotoxicological responses of aquatic macrophytes to 2,4-D based on a PRISMA-guided systematic review of 86 peer-reviewed studies published between 1947 and 2025. A consistent gradient of species-specific sensitivity was observed across macrophyte growth forms. The submerged species Myriophyllum spicatum showed high susceptibility, with EC&#x2085;&#x2080; values of 0.04-0.182 mg/L and marked growth inhibition at low concentrations, whereas floating species such as Lemna minor and Pontederia crassipes were more tolerant, requiring higher concentrations (7.08 to >100 and 8.1 mg/L, respectively) to produce comparable effects. Importantly, this sensitivity ranking was consistent across laboratory and field experimental settings. These interspecific differences likely reflect variation in herbicide uptake, translocation, and detoxification capacity associated with growth form. The overlap between EC&#x2085;&#x2080; values for M. spicatum and regulatory thresholds for 2,4-D in surface waters suggests that current limits may be insufficient to protect sensitive submerged macrophyte communities. Regarding remediation, L. minor and Salvinia natans emerged as the most promising candidates for phytoremediation, while P. crassipes showed limited capacity to reduce herbicide concentrations in water. Despite advances, no study directly compared oxidative stress biomarkers between submerged and floating species, representing a critical gap in understanding the biochemical basis of the sensitivity gradient. Overall, this synthesis highlights the need to account for taxon-dependent sensitivity when evaluating the ecological risks of 2,4-D and provides a basis for improving regulatory frameworks and management of herbicide contamination in freshwater ecosystems.

2,4-Dichlorophenoxyacetic Acid