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PubMed2026

Toxicological effects of propyl 4-hydroxybenzoate on gallstone pathogenesis: An integrated mendelian randomization, network toxicology, and experimental study.

BACKGROUND: Gallstone disease is a prevalent digestive disorder with substantial global socioeconomic burden. Propyl 4-hydroxybenzoate (PP), a widely used paraben preservative, exhibits potential metabolic and hepatic toxicity, yet its role in gallstone pathogenesis remains unclear. This study aimed to explore the causal association between PP exposure and gallstone formation and the underlying mechanism. METHODS: Two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) data. Network toxicology, molecular docking, and molecular dynamics simulation were applied to screen for core targets. In vivo experiments, transcriptome sequencing, Western blot (WB), and ELISA were conducted for mechanistic validation. RESULTS: MR confirmed a causal link between circulating PP levels and an elevated risk of gallstones (P < 0.05), with AKT1 identified as the key target. In mice, PP aggravated gallstone formation by activating the AKT1-NF-κB-CXCL1 pathway, enhancing hepatic inflammation and neutrophil extracellular traps (NETs) formation; these effects were reversed by AKT inhibition. CONCLUSION: PP promotes gallstone formation via the AKT1-NF-κB-CXCL1-NETs axis. Our findings highlight PP as an environmental risk factor for gallstones, providing novel insights into their prevention and targeted therapy.

Animals↗

PubMed2026

Proteomic and phosphoproteomic profiles of time-dependent dynamic changes in LPS-induced macrophage polarization.

The temporal proteomic and phosphoproteomic reprogramming during early M1 macrophage polarization (0-6 h) remains poorly understood. We performed time-resolved proteomic and phosphoproteomic analyses of LPS-stimulated RAW264.7 macrophages at seven time points within 6 h. Time-clustering of differentially expressed molecules revealed two patterns: initial change with partial recovery, and sustained dysregulation. Upregulated proteins and phosphorylation sites were enriched in the Rho GTPase signaling pathway, T-cell receptor signaling pathway, NF-κB cascade, osteoclast differentiation pathway, and antiviral immune pathway. Downregulated pathways were associated with cell cycle regulation, chromatin remodeling, RNA metabolism, and mRNA processing, indicating resource reallocation to prioritize acute inflammatory responses. Kinase-substrate network analysis confirmed the mitogen-activated protein kinase (MAPK), cyclin-dependent kinase (CDK), protein kinase B (AKT), and ribosomal S6 kinase (RSK) families as core upstream phosphorylation regulators. Integrated analysis revealed synergistic and antagonistic relationships between proteomic and phosphoproteomic changes. This study provides a temporal molecular atlas of M1 polarization, delineating inflammatory signaling dynamics and offering a basis for therapeutic target discovery in inflammatory diseases. SIGNIFICANCE: Macrophage M1 polarization is a central event in innate immune defense against pathogenic invasion, yet its dysregulation is a pivotal driver of the onset and progression of a broad spectrum of inflammation-associated disorders, spanning autoimmune diseases, infectious conditions and inflammatory bone diseases, making the dissection of its molecular regulatory mechanisms an urgent research priority in immunology and translational medicine. Dynamic molecular events within 0-6 h after LPS stimulation are critical for initiating and shaping M1 inflammatory activation, yet systematic time-resolved proteomic and phosphoproteomic profiling remains insufficient.In this study, we comprehensively characterized temporal proteome and phosphoproteome changes at seven consecutive time points during macrophage polarization, clarified two distinct dynamic molecular patterns, identified core signaling pathways and key kinase regulators involved in inflammatory reprogramming, and uncovered the leading role of post-translational phosphorylation modifications in initiating polarization. This work delineates the time-series molecular atlas of early macrophage activation, provides novel insights into the temporal regulatory mechanism of inflammatory signaling networks, and lays a solid experimental foundation for exploring new intervention targets and regulatory nodes in clinical translational research.

Lipopolysaccharides↗

PubMed2026

Human iPSC-EV-loaded nanofiber stent coatings accelerate vascular repair by enhancing EGFR/HIF-1α signaling and suppressing ROCK1-mediated remodeling.

Arterial disease management is shifting from antiproliferative drug-eluting stents toward approaches that restore endothelial function and modulate smooth muscle cell (SMC) behavior. Stem cell-derived extracellular vesicles (EVs) carry miRNAs that promote endothelial proliferation and migration while restraining aberrant SMC growth and inflammation. Here, human induced pluripotent stem cell (iPSC)-derived EVs were collected by ultracentrifugation and incorporated into 50:50 poly (lactic-co-glycolic acid) (PLGA 503) core-shell nanofibrous membranes, which were fabricated as stent coatings for sustained release to overcome rapid clearance and poor tissue retention. EVs derived from three independent iPSC lines all enhanced tube formation in human umbilical vein endothelial cells (HUVECs) under hypoxic and serum-starved conditions and revealed a trend toward reduced platelet-derived growth factor-BB (PDGF-BB)-induced smooth muscle cell (SMC) migration. The fabricated core-shell nanofibers enabled sustained EV release, maintaining therapeutic efficacy for 28 days. Small RNA sequencing (NGS) analysis demonstrated that EVs from these independent iPSC lines shared miR-148a-3p and members of the miR-92 family, which collectively accounted for more than 75% of the reads within the 25 top-expressed miRNA set. In vitro, iPSC-EVs enhanced HUVEC proliferation and survival signaling by downregulating the negative regulators ERRFI1 and VHL, which are specific targets of miR-148a-3p and the miR-92 family, thereby activating the EGFR and HIF-1α axes and driving downstream ERK1/2 and VEGF expression under hypoxic and serum starvation stress conditions. Concurrently, iPSC-EVs prevented PDGF-BB-induced SMC phenotypic switching by downregulating ROCK1, a target of miR-148a-3p, thereby inhibiting downstream AKT and ERK signaling and preserving contractile markers while suppressing the synthetic phenotype. In vivo, the iPSC-EV-functionalized scaffolds significantly accelerated re-endothelialization and inhibited neointimal hyperplasia, evidenced by the upregulation of angiogenic factors (VEGF, CD31) and the concurrent suppression of pathological remodeling markers (α-SMA, MMPs) and inflammatory cytokines (IL-6, TGF-β1). Therefore, iPSC-EVs enriched with specific miRNAs and delivered via PLGA 503 core-shell nanofibers promote endothelial repair while suppressing SMC overgrowth, providing a promising strategy for vascular healing.

Core-shell nanofibers↗

PubMed2026

A novel peptide encoded by circTLL1 drives osimertinib resistance in lung cancer by modulating the NT5C2/Ras/PI3K axis.

BACKGROUND: Acquired resistance to osimertinib, a third-generation EGFR tyrosine kinase inhibitor, remains a major clinical challenge in the treatment of non-small cell lung cancer (NSCLC). Although circular RNAs (circRNAs) have been increasingly implicated in drug resistance, most studies have focused on their canonical role as microRNA sponges, while their capacity to encode functional micropeptides remains largely unexplored. This study aimed to identify novel circRNAs involved in osimertinib resistance and to characterize their regulatory functions at the protein level. METHODS: Osimertinib-resistant (OR) NSCLC cell lines were established and validated. High-throughput RNA sequencing was performed to compare the circRNA expression profiles between parental and OR cells. The function of the candidate circRNA was assessed through a series of in vitro and in vivo experiments, including cell viability assays, apoptosis analysis, and xenograft mouse models. Mechanistic investigations involved mass spectrometry, co-immunoprecipitation and western blotting to explore its protein-coding potential and downstream signaling pathways. RESULTS: We identified a novel circRNA, termed circTLL1, that was stably and significantly upregulated in OR-NSCLC cells. Functionally, overexpression of circTLL1 promoted osimertinib resistance, whereas its knockdown restored drug sensitivity both in vitro and in vivo. Mechanistically, we discovered that circTLL1 harbors an open reading frame (ORF) that is translated into a novel 90-amino-acid protein, which we designated circTLL1-90aa. Further investigation revealed that circTLL1-90aa directly interacts with and promotes the degradation of 5'-nucleotidase, cytosolic II (NT5C2), thereby uncoupling nucleotide metabolism from its normal regulatory constraints. The consequent downregulation of NT5C2 leads to elevated GTP levels and leading to the sustained activation of the downstream Ras/PI3K/AKT signaling pathway. CONCLUSION: Our findings unveil a previously unrecognized circRNA/micropeptide/metabolism cascade underlying osimertinib resistance. The identification of the circTLL1-90aa/NT5C2/Ras/PI3K axis not only expands the functional repertoire of the non-coding genome but also provides new insights into the complexity of drug resistance. Given its selective upregulation in resistant cells, circTLL1-90aa holds promise both as a predictive biomarker for treatment stratification and as an actionable therapeutic target, offering a novel strategy to overcome osimertinib resistance in NSCLC patients.

Pyrimidines↗

PubMed2026

Three-dimensional porous nano-hydroxyapatite@gelatin composite as efficient adsorbent for uranyl ion removal from low-level radioactive wastewater.

The contamination of water resources by uranyl (UO22+) ions poses significant environmental and health risks, requiring the development of efficient and sustainable remediation strategies. Adsorption-based techniques have emerged as promising approaches in the field of UO22+ removal, but the design of cost-effective, high-capacity, and environmentally friendly adsorbents remains challenging. In this study, a three-dimensional porous nano-hydroxyapatite@gelatin (nHAP@Ge) composite was synthesized through glutaraldehyde cross-linking, combining the structural stability of Ge with the high uranium affinity of nHAP. The optimized nHAP@Ge, with a nHAP:Ge mass ratio of 1:0.5, exhibited exceptional UO22+ removal efficiency (97 %), along with high adsorption capacity (364.03 mg/g). Systematic characterizations using scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, and X-ray photoelectron spectroscopy (XPS) methods revealed that the porous structure and surface functional groups (-OH, Ca2+, and PO43-) of the material synergistically contributed to binding UO22+ species. Furthermore, the incorporation of nHAP into the Ge framework resulted in enhanced thermal stability while significantly improving the UO22+ adsorption performance. This work presents a scalable, eco-friendly, and recyclable strategy for the effective treatment of uranium-contaminated water, with potential applications in nuclear wastewater treatment and environmental remediation.

Adsorption↗

PubMed2026

Divergent responses of the gill, hepatopancreas, and eyestalk to acute alkalinity stress in Penaeus vannamei: Osmoregulatory compromise, metabolic trade-off, and endocrine disruption.

The expansion of aquaculture into inland saline-alkali waters is constrained by high carbonate alkalinity (CA), a severe environmental stressor for crustaceans. However, the systemic molecular mechanisms underlying its lethal toxicity remain poorly understood. In this study, we employed a comparative transcriptomic approach to investigate the tissue-specific responses of Pacific white shrimp, Penaeus vannamei, under acute lethal stress (48 h-LC50). We focused on three functionally distinct organs: the gill, hepatopancreas, and eyestalk. The results revealed a systemic but highly tissue-specific transcriptomic response. The gill, as the primary interface, exhibited severe structural impairment and critical failure of osmoregulation, highlighted by the significant downregulation of delta-1-pyrroline-5-carboxylate synthetase (P5CS). In contrast, the hepatopancreas initiates a profound metabolic trade-off, sacrificing growth-related pathways to bolster a robust antioxidant defense system, as evidenced by the activation of sulfur metabolism and high protein turnover. The eyestalk displayed a striking disconnect between hyperactivated stress signaling pathways (e.g., mTOR/FoxO) and the collapse of its protein secretory machinery, marked by the suppression of the ER translocon component Sec61. Collectively, our findings suggest that lethal alkalinity toxicity in P. vannamei results from systemic collapse driven by a complex interplay of osmoregulatory failure, metabolic trade-offs, and endocrine disruption. This study provides a comprehensive molecular snapshot of an organism at its physiological limit, offering novel insights into the adaptive strategies and ultimate tolerance boundaries of crustaceans in extreme environments.

Animals↗

PubMed2026

Discrepancies in CPAK classification between CT and long-leg radiography: a systematic review and meta-analysis.

OBJECTIVE: To determine whether substantial differences in coronal plane alignment of the knee phenotype distribution, as well as systematic angular measurement discrepancies, exist between CT and long-leg radiography. MATERIALS AND METHODS: From February 2021 to April 2025, we searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for studies comparing CT- and long-leg radiography-derived coronal plane alignment classifications of the knee in patients with osteoarthritis. The primary outcome was distribution of coronal plane alignment phenotypes. Secondary outcomes included differences in medial proximal tibial angle, lateral distal femoral angle, arithmetic hip-knee-ankle angle, and joint line obliquity. RESULTS: Four studies (1,134 knees) were included. Compared with long-leg radiography-derived classification, CT-derived classification increased type I phenotypes (risk difference: 0.10; 95% confidence interval: 0.01-0.20; P = 0.040) and decreased type III (risk difference: -0.04; 95% confidence interval: -0.07 to -0.01; P = 0.020) and type V phenotypes (risk difference: -0.04; 95% confidence interval: -0.07 to -0.01; P = 0.004). CT yielded significantly lower medial proximal tibial angle (weighted mean difference: - 1.18°; P < 0.001), arithmetic hip-knee-ankle angle (weighted mean difference: - 0.95°; P < 0.001), and joint line obliquity (weighted mean difference: - 1.40°; P < 0.001) than long-leg radiography. Heterogeneity was high for type I phenotype (I2 = 81%), lateral distal femoral angle (I2 = 70%), and joint line obliquity (I2 = 69%). CONCLUSION: Discrepancies between CT-based software-generated and long-leg radiography-derived measurements substantially affect coronal plane alignment classification and angular parameters. Surgeons should consider these modality-specific variations and employ compensatory verification strategies to ensure optimal alignment.

Humans↗

PubMed2026

Transcriptomics reveals species-specific adaptive strategies to calorie restriction in two Argopecten scallops with distinct lifespans.

Calorie restriction (CR) is a well-established non-genetic intervention for lifespan extension in multiple model organisms. Seasonal food shortage in cold and temperate seas may mimic CR, inducing in bivalves a response similar to that in vertebrates and thereby prolonging life expectancy. However, the relationship and the mechanism underlying the food availability and lifespan in bivalves remain largely unexplored. Two closely related scallop species the short-lived warm-water Argopecten irradians (lifespan <2 years) and the longer-lived cold-water Argopecten purpuratus (7-10 years) provide an ideal comparative system to investigate species-specific adaptive strategies. In this study, we subjected both species to CR for 30 and 56 days and performed comparative transcriptomic profiling, weighted gene co-expression network analysis (WGCNA), and physiological assays to elucidate their distinct molecular responses. Transcriptomic analysis revealed that A. purpuratus exhibited substantially more DEGs than A. irradians at both time points under CR, with both species showing downregulation of metabolic pathways but to different extents. A. irradians mounted an early nutrient-sensing response at 30 days (IGF1R, PIK3R3, INSR suppression), indicating acute sensitivity to limitation; by contrast, A. purpuratus displayed delayed FoxO activation at 56 days, along with its downstream effectors NFKBIA, CREB3L4, and SMAD4, suggesting a gradual adaptive program may link to its extended lifespan. WGCNA identified three negatively correlated modules in each species, with coral2 being the most prominent in A. irradians and darkolivegreen in A. purpuratus. The former was dominated by ciliary motility genes, whereas the latter featured coordinated repression of oxidative phosphorylation. Additionally, both species exhibited conserved suppression of mTOR/S6K growth signaling and activation of cellular maintenance programs. Collectively, these findings expand the understanding of CR-mediated longevity regulation in bivalves and provide candidate gene resources for future functional studies and breeding programs.

Pectinidae↗

PubMed2026

Morphology-Encoded Colorimetric Hydrogen Sensing Using Embedded Reactive Pd Absorbers in Fabry-Perot Cavities.

Chemical reactions offer a powerful strategy for generating visible optical responses through localized changes in absorption, dielectric environment, and interfacial wetting. A palladium (Pd)-embedded Fabry-Perot cavity is introduced as a reaction-active optical platform in which structural color is governed by intracavity absorption coupled with reaction-induced dielectric perturbation. Positioning Pd within the dielectric spacer creates a spatially controllable reactive absorber whose vertical location relative to the standing-wave field dictates wavelength-selective absorption within the cavity. The morphology of the embedded Pd layer provides an additional design parameter by modulating both optical loss and interfacial wetting. Under hydrogen exposure in the presence of oxygen, catalytic water formation at the Pd/polymer interface generates localized dielectric heterogeneity and interfacial water droplets, thereby perturbing the optical path length and amplifying the visible response. As a result, the cavity exhibits pronounced, morphology-dependent color transitions that are inaccessible through dielectric-layer engineering or Pd/PdH refractive-index changes alone, enabling direct visual hydrogen sensing under ambient light, as well as flexible optical devices capable of large-area patterning. These findings establish a design framework for reaction-active optical cavities that translate localized chemistry into a colorimetric hydrogen sensing mechanism.

Fabry–Perot resonator↗

PubMed2026

Chemical and sensory profiling of fermented, washed, and artificially flavored coffee beans: Insights into flavour quality, authenticity, and food safety implications.

This study establishes an integrated framework combining chemical profiling, sensory analysis, and molecular mechanism evaluation to compare flavour quality and authenticity among fermented, washed, and artificially flavored coffees. GC × GC-TOF-MS and UHPLC-HRMS showed that fermented samples had markedly higher ester and aromatic alcohol levels (total esters 74.5 ± 7.8 mg kg-1; phenylethanol 27.5 ± 3.2 mg kg-1, p < 0.01), enhancing fruity-floral notes. Washed coffees contained the highest organic acid concentrations (45.2 ± 3.8 mg kg-1, p < 0.01), supporting brightness and umami. Artificially flavored coffees exhibited elevated exogenous aromatics (vanillin 21.5 ± 3.1 mg kg-1) but significantly fewer Maillard products (p < 0.05) and reduced flavour retention (55% after 14 days). Molecular docking revealed higher theoretical binding affinities for naturally generated compounds, suggesting a potential molecular basis for their greater sensory persistence. The framework supports constructing coffee quality fingerprints and verifying flavour authenticity.

Flavoring Agents↗

PubMed2026

Clinical Outcomes and Patient Experiences With Celiprolol Therapy in Vascular Ehlers-Danlos Syndrome: The First Non-European Cohort.

Vascular Ehlers-Danlos syndrome (vEDS) is a hereditary connective tissue disorder caused by heterozygous pathogenic variants in COL3A1. European studies have shown that celiprolol may reduce the risk of life-threatening vascular events, but outcomes in non-European populations and the therapy's psychological impact remain unclear. We conducted a retrospective cohort study of individuals aged ≥ 20 years with genetically confirmed vEDS in a single referral center in Japan between 2000 and 2024. Clinical, molecular, and treatment data were obtained from medical records, and semi-structured interviews were conducted with a subset of participants to assess patient experiences. Twenty-six patients were included. The mean age at celiprolol initiation was 36.9 years, with a mean follow-up of 96.6 months. All patients received celiprolol, and 61.5% reached the target dose (400 mg/day). One patient died of hepatic artery rupture; vascular events occurred in 11, while 14 remained event-free. No significant associations were observed between vascular event occurrence and genotype or celiprolol dose. Interviews with 11 patients revealed that celiprolol use provided emotional reassurance and promoted a more proactive approach to disease management. Celiprolol therapy may reduce fatal vascular events in vEDS and have a positive psychological impact, though nonfatal vascular complications remain frequent.

Humans↗

PubMed2026

Mitigating pH-induced instability in deruxtecan-based ADCs: an onboard-mixing icIEF approach for robust charge heterogeneity characterization.

Accurate charge variant analysis of antibody-drug conjugates (ADCs) is essential for understanding product heterogeneity and ensuring quality control. However, Deruxtecan (DXd)-based ADCs present a unique analytical challenge due to the intrinsic instability of the payload, where the lactone ring readily undergoes hydrolysis under alkaline conditions, resulting in time-dependent shifts in charge distribution during imaged capillary isoelectric focusing (icIEF). In this study, we describe the development of an onboard-mixing icIEF method designed to minimize pH-induced degradation during sample preparation. By separating ADC samples from carrier ampholytes (CAs) prior to injection and enabling real-time mixing within the instrument, this approach effectively suppresses premature lactone ring opening and stabilizes charge variant profiles. Comparative studies between conventional premixing and onboard-mixing approach demonstrated that the latter significantly enhances reproducibility, particularly for acidic variants that are highly sensitive to structural conversion. Comprehensive method validation confirmed excellent precision, linearity, and sensitivity, with consistent performance across run-to-run and intra-day analyses. The results underscore the importance of controlling microenvironmental pH exposure in the analysis of chemically instable ADCs. The proposed onboard-mixing strategy provides a robust and efficient solution for icIEF-based characterization, reducing analytical artifacts while simplifying method development. This approach is broadly applicable to ADCs and other biotherapeutics containing pH-sensitive functional groups.

Hydrogen-Ion Concentration↗

PubMed2026

The relationship between composite dietary antioxidant index and odds of depression: A systematic review and dose-response meta-analysis of observational studies.

BACKGROUND: Recently, the association between the composite dietary antioxidant index (CDAI) score and depression has received special attention from researchers. However, this possible association has not been comprehensively examined. Thus, the present study aims to comprehensively assess the relationship between CDAI score and depression odds. METHODS: A thorough literature search was performed using Scopus, PubMed, and Web of Science up to November 2025. Observational studies assessing the relationship between CDAI score and depression odds were included. The odds ratios (ORs) and their 95% confidence intervals (CIs) reported in each study were extracted, and a pooled effect size was calculated using a random-effects model with inverse-variance weighting. RESULTS: Four observational studies were included in the current systematic review and meta-analysis. The pooled effect size indicated that a higher CDAI score was associated with lower odds of depression (OR:0.62; 95%CI: 0.51-0.76, I2 = 48.5%; P-value = 0.121). In an exploratory linear dose-response analysis based on two eligible studies, no significant association was observed between a one-unit increase in CDAI score and the odds of depression (OR = 0.96; 95% CI: 0.91-1.02; I2 = 92.2%; P-value<0.001). Given the limited number of studies and substantial heterogeneity, these findings should be interpreted cautiously. CONCLUSIONS: Our findings suggest that higher CDAI scores, reflecting greater adherence to antioxidant-rich dietary patterns, are associated with lower odds of depression.

Humans↗

PubMed2026

Association between fruit and vegetable intake and risk of depression: A systematic review and meta-analysis of prospective cohort studies.

Depression is a leading cause of global disability, and identifying modifiable lifestyle factors is a public health priority. We conducted a systematic review and dose-response meta-analysis of prospective cohort studies examining the association between fruit and vegetable intake and incident depression. PubMed, Web of Science, Scopus, Embase, and Google Scholar were searched through November 2025. Data on study characteristics, dietary assessment, outcomes, effect estimates, and covariates were independently extracted by two reviewers. Random-effects models were used to calculate pooled relative risks (RRs), and linear and non-linear dose-response relationships were assessed. Heterogeneity was evaluated using I2, and evidence certainty was rated with GRADE. Thirteen cohorts with 385,449 participants and 26,592 depression cases were included. Highest versus lowest combined fruit and vegetable intake was associated with a 37% lower risk of depression (RR: 0.63; 95% CI: 0.50, 0.80). Each 200 g/day increase corresponded to a 16% risk reduction (RR: 0.84; 95% CI: 0.74-0.94). Separate analyses showed that fruit and vegetable intake reduced depression risk by 16% and 12%, respectively, with a non-linear dose-response for vegetables. These findings indicate that higher consumption of fruits and vegetables is associated with lower depression risk, supporting dietary strategies as a potential approach for mental health prevention. However, given the observational nature of the included studies, these results should be interpreted with caution, as residual confounding may partially account for the observed associations. Registration: This study was registered at PROSPERO (CRD420261279998).

Humans↗

PubMed2026

Quantifying the aromatic amino acid metabolome: UPLC-MS/MS analysis of aromatic amino acids and their host and co-metabolites in plasma.

Aromatic amino acids (AAAs), tryptophan, phenylalanine, and tyrosine along with their pathway metabolites have been implicated in the pathogenesis of diseases ranging from cardiovascular, neurological, inflammatory, and cancer diseases, among others. As such, the measurement of the primary AAAs, their host pathway metabolites, and microbiome derived co-metabolites in blood can provide a sensitive reflection of systemic health. The aim of the study was to develop a method for the quantification of 17 metabolites, the three AAAs and various of their metabolites in plasma using a high-throughput ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. The method demonstrated a dynamic range (1 to 16,700 ng/mL), with detection limits (LOD) as low as 0.05 ng/mL. Quantification limits ranged from 3 to 5019 ng/mL (LLOQ) and up to 16,700 ng/mL (ULOQ). Recovery at LQC, MQC, and HQC was satisfactory and consistent across most metabolites, with significant matrix effects observed only for 4-ethylphenol sulfate. Furthermore, intra and inter-day accuracy and precision met all acceptance criteria at all quality control concentrations for most of the metabolites. Measurement of NIST SRM 1950 showcased the method's accuracy for most of the metabolites. Finally, the method was applied on the analysis of plasma samples from 55 individuals (13 males and 42 females) providing information on AAAs and their pathway metabolites relevant concentrations in human plasma.

Amino Acids, Aromatic↗

PubMed2026

Effects of rumen fluid transplantation on longissimus dorsi muscle development in Xizang sheep: An association analysis based on transcriptomic and serum metabolomic profiles.

This study aimed to investigate the effects of rumen fluid transplantation (RFT) on the growth and development of the longissimus dorsi muscle in female Xizang sheep. After RFT, muscle lightness differed significantly between the two groups, with the LDC group showing significantly higher lightness than the LDT group. In contrast, no significant differences were observed between groups in other muscle phenotypic traits, including drip loss, pH, cooking loss, shear force, redness, and yellowness. Antioxidant-related indices (SOD, GSH-PX, MDA, CAT, and T-AOC) also showed no significant differences between groups. Histological analysis revealed that muscle fiber length, width, and density were significantly greater in the experimental group than in the control group. Transcriptomic analysis identified 515 differentially expressed genes (DEGs), of which 419 were downregulated. KEGG analysis indicated that genes involved in muscle development-related pathways, such as cell adhesion and the PI3K-Akt signaling pathway, were predominantly downregulated. Key serum metabolites (L-kynurenine, IPA, allantoin, and propionylcarnitine) showed highly significant positive correlations with muscle fiber growth indices. In contrast, metabolites such as l-carnitine, acetylcarnitine, and citrulline were negatively correlated with muscle fiber growth, but positively correlated with the expression of muscle structure-related genes (COL11A1 and EFNA5) and with meat lightness. Overall, this study provides new insights into the potential molecular basis by which RFT influences muscle growth and development. However, the mechanisms by which RFT affects muscle development and meat quality-related traits remain unclear and warrant further investigation.

Animals↗

PubMed2026

Transcriptomic changes in the gut mucosa of fasting northern elephant seal pups reveal immune modulation during early microbiome establishment.

Fasting is an integral component of the life-history of many species. Following abrupt weaning, northern elephant seal pups (Mirounga angustirostris) undergo an extended post-weaning fast of approximately 60 days. During this period, enteric bacterial diversity increases, suggesting that host immune regulation may facilitate the establishment of microbial communities. However, the molecular processes occurring within the intestinal mucosa during this transition remain poorly understood. To investigate these mechanisms, we characterized transcriptional changes in the enteric mucosa of male and female northern elephant seal pups sampled at weaning and after one month of fasting. Total RNA isolated from rectal swabs was sequenced and aligned to the Mirounga angustirostris reference genome. Differential gene expression and gene set enrichment analyses were used to identify genes and pathways associated with fasting and sex-specific responses. Fasting was accompanied primarily by transcriptional downregulation, including genes involved in antimicrobial defense, inflammation, protein turnover, and epithelial remodeling. In contrast, several genes associated with B-cell activity and immune recognition were upregulated. Gene Set Enrichment Analysis revealed coordinated activation of immune-regulatory pathways indicating dynamic modulation of intestinal immunity rather than generalized immune suppression. Pronounced sex-specific differences were also observed. Male pups exhibited transcriptional patterns consistent with enhanced immune tolerance, whereas females showed broader immune-pathway activation, including enrichment of pro-inflammatory and stress-response pathways. Several non-coding RNAs also displayed sex-specific changes in expression. Together, these findings suggest that fasting induces transcriptional remodeling of the gut and may contribute to immune regulation during a critical period of microbiome establishment in northern elephant seal pups.

Animals↗

PubMed2026

Optimal dose and exercise modality to improve HbA1c in older adults with type 2 diabetes mellitus: a systematic review with pairwise, network, and dose-response meta-analyses.

We aimed to compare exercise modalities and evaluate dose-response relationships with glycemic control including continuous aerobic exercise (CAE), resistance training (RT), combined exercise (CE), mind-body exercise (MBE), and high-intensity interval training (HIIT) in older adults with type 2 diabetes mellitus (T2DM). Three databases were searched for randomized controlled trials of exercise interventions in older adults with T2DM reporting glycated hemoglobin (HbA1c). Pairwise, Bayesian network, and dose-response meta-analyses were conducted. Compared with control, HIIT demonstrated the largest estimated reduction (MD = -0.95%; 95% CrI -1.45, -0.49), followed by CE (MD = -0.59%; 95% CrI -0.93, -0.25), CAE (MD = -0.46%; 95% CrI -0.69, -0.24), MBE (MD = -0.42%; 95% CrI -0.76, -0.10), and RT (MD = -0.29%; 95% CrI -0.51, -0.08). Dose-response network meta-analyses suggested a non-linear association between overall exercise dose and HbA1c reduction, with maximal estimated benefits at approximately 704 METs-min/week with the 95% CrI excluding zero between 241 and 920 METs-min/week. HIIT demonstrated the steepest estimated dose-response relationship, but with wider credible intervals. Other exercise modalities showed more gradual dose-response patterns across their estimated effective ranges. Our findings suggest that exercise prescription for older adults with T2DM should be individualized according to exercise modality, dose, and health status.

Humans↗

Results for “Akt&#x2013;mTOR signaling”

Results for “Akt–mTOR signaling”