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PubMed2026

Genome-wide insights into the evolutionary and demographic history of the red alga Mazzaella laminarioides: Evidence for speciation with ancient migration along the southeast Pacific coast.

The mechanisms driving lineage divergence in red algae remain unexplored, despite the group's remarkable diversity and ancient evolutionary history. The red alga Mazzaella laminarioides, a Chilean intertidal species complex composed of three parapatric cryptic lineages (North, Center, South), offers a valuable system to evaluate these processes, as its life history combines severe dispersal limitation with a haploid-diploid cycle that may influence the emergence of reproductive barriers. We reconstructed its evolutionary history using whole-genome sequencing and nuclear genome assembly of representative individuals from each lineage. Phylogenomic analyses based on 1,507 single-copy orthologs recovered three deeply divergent lineages with limited nuclear discordance consistent with incomplete lineage sorting. For both splits, demographic modelling was most consistent with an Ancient Migration scenario, although support over strict isolation was moderate, suggesting that divergence may have begun with low asymmetric ancestral gene flow followed by subsequent loss of connectivity, demographic bottlenecks, and later population expansion. Coding sequence analyses revealed lineage-specific dN/dS heterogeneity; only one South-lineage locus passed FDR correction (metaxin-1, mitochondrial protein import), with two further South-lineage candidates in chlorophyll and heme biosynthesis falling below the FDR threshold. Together, these signals suggest that divergent selective pressures on energy acquisition may have contributed to divergence at the southern end of the distribution. These results add to the small but growing body of whole-genome data for red algae and, alongside recent macroalgal studies, suggest that ancestral connectivity could be a recurrent feature of lineage divergence even in marine organisms with extremely restricted dispersal.

Rhodophyta↗

PubMed2026

Comparative analyses of olfactory receptor repertoires in Schizothorax fish based on the chromosome-level genomes: Implications for regulatory roles of dietary differentiation and ploidy variation.

The olfactory receptor (OR) genes constitute the molecular basis of fish olfaction, mediating survival behaviors and environmental adaptation while coevolving with habitat-driven evolution. Schizothorax, a cyprinid genus endemic to the Qinghai-Tibetan Plateau, exhibits remarkable dietary divergence and ploidy variation in response to plateau environmental changes, which presumably facilitates the adaptive evolution of OR genes. However, the evolutionary patterns of OR genes associated with trophic divergence and ploidy variation in this genus remain unclear. In this study, three species were selected: the herbivorous diploid S. macropogon, the carnivorous diploid S. lantsangensis, and the herbivorous tetraploid S. curvilabiatus. S. macropogon possessed 142 OR genes (92.25% functional), primarily located on chromosomes 14 and 24, with the fewest sequence clusters. Such compact gene repertoire and highly overlapping chromosomal clusters indicated specialization for a herbivorous olfactory niche. S. lantsangensis contained 127 OR genes (93.70% functional), concentrated on chromosomes 4 and 5, with fewer sequence clusters and a scattered distribution, reflecting evolution of OR genes under carnivorous feeding habits. The herbivorous tetraploid S. curvilabiatus exhibited striking features: 316 OR genes (94.30% functional), the most subfamilies, unique ε and κ OR subfamilies, and species-specific motifs. These characteristics revealed that ploidy, rather than herbivory, dominated OR gene evolution. In conclusion, dietary differentiation and ploidy variation together drove olfactory adaptive evolution in Schizothorax, providing new insights into vertebrate OR gene ecological adaptation.

Animals↗

PubMed2026

Selective monitoring of trace-level catechin and myricetin in herbal and aqueous matrices using magnetic MIP-DSPME: Optimization via design of experiments.

A novel dispersive solid-phase microextraction approach utilizing a magnetic molecularly imprinted polymer (MMIP) integrated with HPLC-UV detection was developed for the concurrent quantification of catechin and myricetin in herbal extracts and aqueous samples. The sorbent was engineered as a core-shell nanocomposite, consisting of a selective polymer layer deposited onto Fe3O4@SiO2-APTMS magnetic nanoparticles. Dual-template imprinting using catechin and myricetin generated complementary binding cavities within the polymer framework. Experimental variables influencing extraction were systematically screened and subsequently optimized. A Plackett-Burman design was first applied to identify the most influential factors, with pH and sorption time identified as the dominant variables. These parameters were subsequently fine-tuned using a central composite design, and the optimization process was completed in only 30 experimental runs. The sorption characteristics of the imprinted sorbent (MMIP) were compared with those of its non-imprinted counterpart (MNIP). The MMIP demonstrated markedly higher maximum binding capacities (Qmax), reaching 119.3 mg g-1 for myricetin and 112.1 mg g-1 for catechin, whereas the corresponding values for the MNIP were 32.55 and 32.08 mg g-1, respectively. Moreover, the affinity constants (KL = 0.760-0.950 L mg-1) were approximately 2.3-fold higher for the MMIP, confirming its stronger and more selective interactions with the target analytes. The selectivity coefficients for the targeted flavonoids relative to structurally related compounds, including ferulic acid, p-coumaric acid, melatonin, and curcumin, exceeded 3.5 for the MMIP, whereas the corresponding values for the MNIP were close to 1.1, demonstrating the high molecular recognition capability of the imprinted sorbent. Method validation demonstrated limits of detection (LODs) of 0.33-0.59 ng mL-1 and limits of quantification (LOQs) of 1.10-1.96 ng mL-1, and excellent linearity over the concentration range of 5.0-5500 ng mL-1 (R2 > 0.998). The method achieved recoveries of 93.96% to 105.69% with RSDs below 5.5%, while the preconcentration factors ranged from 209 to 229. Furthermore, the sorbent retained more than 95% of its extraction efficiency after four consecutive reuse cycles and more than 80% after six cycles, demonstrating excellent stability and reusability. The proposed method was successfully applied to the analysis of six medicinal plant extracts and water samples, showing negligible matrix interference and superior sensitivity, selectivity, and operational simplicity compared with conventional solid-phase extraction methods.

Flavonoids↗

PubMed2026

Determination of 13 per- and polyfluoroalkyl substances in human plasma samples using LC-MS/MS: application to capillary microsamples.

Per- and polyfluoroalkyl substances (PFAS) are chemicals widely applied in industrial processes and highly persistent in the environment, whose extensive use has been linked to adverse health effects. Venous plasma is the conventional matrix for PFAS assessment in blood, and LC-MS/MS is the most used quantification technique. Despite the relevance of this topic, biomonitoring data on human exposure to PFAS in Brazil remain limited. This study validated an LC-MS/MS method for determination of 13 PFAS in human plasma. Blood samples were collected from volunteers by phlebotomy, followed by protein precipitation with acetonitrile containing 1% formic acid (v/v) and solid-phase extraction. Chromatographic separation was achieved on an Acquity UPLC HSS T3 column. The assay was linear over a calibration range of 0.2-20 ng/mL. Intra- and inter-assay precision (CV%) were within the ranges of 2.06-12.0% and 0.25-10.7%, respectively. As for accuracy, results were 89.0-112.9%. Matrix effect ranged from -1.31 to 0.05%. Stability after four freeze/thaw cycles and under autosampler conditions were also confirmed for all analytes. The method was applied to 40 paired venous and capillary plasma samples. Both measures exhibited high correlation (r = 0.926). PFOS was the only compound detected at concentrations ≥0.2 ng/mL (LLOQ) in all samples, with capillary plasma concentrations of 0.85-13.50 ng/mL. In summary, the method showed good validation performance and demonstrated the suitability of capillary plasma samples as an alternative matrix for PFAS quantification.

Humans↗

PubMed2025

Depth-dependent multi-kingdom microbial interactions and biogeochemical cycling genes in eutrophic shallow lake sediments.

Microorganisms are pivotal to lake ecosystem biogeochemical cycles, yet existing research often focuses on single microbial kingdoms or surface sediments, neglecting multi-kingdom interactions and depth-resolved dynamics. To address these gaps, we used metagenomic sequencing to characterize microbial communities and their functional associations across overlying water and 0-45 cm sediments in four shallow lakes of the middle Yangtze River basin, China. Despite increasing bacterial and fungal diversity with depth, the 0-9 cm surface sediments exhibited the strongest multi-kingdom network connectivity and the greatest microbial stability. Functional genes exhibited clear depth-dependent patterns: nitrogen cycling genes, including those involved in dissimilatory nitrate reduction to ammonium, were most enriched in the upper 0-9 cm of sediment; methane cycling genes were positively correlated with depth; phosphorus cycling genes and some sulfur cycling genes, such as assimilatory sulphate reduction, declined with depth. Sediment microbial assembly was dominated by deterministic processes, in which the vertical distribution of functional genes was primarily dictated by heavy metals and conventional environmental indicators. These findings highlight depth-specific multi-kingdom microbial interactions and their associations with biogeochemical cycling, advancing lacustrine microbial ecology understanding and providing references for lake conservation under environmental change.

Lakes↗

PubMed2026

A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.

INTRODUCTION: Cancer cell proliferation occurs within the context of persistent genomic instability. In this review, we propose the RS-CCD-CIN axis as a systems-level framework in which replication stress (RS), cell cycle deregulation (CCD) and chromosomal instability (CIN) form an interdependent triad that shapes tumour evolution. This axis represents a constrained metastable state in which genomic instability is tolerated and buffered. The objective of this review is to synthesize the current understanding of how the RS-CCD-CIN axis contributes to tumour heterogeneity, adaptability and therapy response. DISCUSSION: Evidence indicates that RS, CCD and CIN operate as a dynamic, interconnected network rather than as independent processes. Replication stress induces DNA damage and mutagenesis, while partial checkpoint disruption permits cells with unresolved lesions to proliferate. Chromosomal instability generates both structural and numerical alterations, contributing to intratumoural heterogeneity. Together, these processes facilitate adaptation to environmental and therapeutic pressures. Extrachromosomal DNA, micronuclei formation and cytosolic DNA signalling, including the cGAS-STING pathway, connect genomic instability to adaptive responses and immune modulation. Single-cell and spatial profiling reveal temporal and spatial variability in RS, CCD and CIN states, highlighting the limitations of static biomarkers. Therapeutically, targeting individual components often yields limited durability, whereas approaches that simultaneously perturb multiple aspects of the RS-CCD-CIN axis may improve clinical outcomes. CONCLUSIONS: This review highlights the RS-CCD-CIN axis as a fragile and metastable architecture that supports cancer evolution, while also being susceptible to collapse. A deeper understanding of this interconnected framework may inform the development of therapeutic strategies and enhance the management of resistance.

Humans↗

PubMed2026

Cytonuclear conflict and reticulate evolution in the Morelloid clade (Solanum, Solanaceae): Insights from genome skimming and network Phylogenomics.

The Morelloid clade (black nightshades) is one of the most strongly supported clades within the megadiverse Solanum genus. It comprises 76 globally distributed, non-spiny herbaceous and suffrutescent species. While often erroneously considered poisonous weeds, several species are economically important as orphan crops. The clade is closely related to tomato and potato but, due to a lack of focused breeding efforts, remains a putative reservoir of genetic diversity for crop improvement. Despite this potential, we lack fundamental knowledge on the evolution of the Morelloid clade. The group includes polyploid species with unknown parental origins-likely reflecting reticulate processes such as hybridization, introgression, and associated backcrossing events. Prior analyses have been unable to disentangle these processes, leaving the mechanisms underlying reticulate evolution in the Morelloid clade poorly understood. Here, we use genome skimming to produce a well-supported maximum likelihood plastid phylogeny from complete circularized plastomes and a coalescent-based species tree from combined Angiosperms353 and conserved ortholog set nuclear markers. Our dataset, composed of previously published data and deep genome skimming from herbarium samples, spans 26 Morelloid species. To investigate phylogenetic discordance, we used a nuclear phylogenetic network, multispecies coalescent simulations, a fused rooted nuclear chloroplast tree, and quantification of nuclear gene tree concordance. We show that incongruence between nuclear and plastid trees is pervasive and cannot be explained by incomplete lineage sorting alone. Instead, our results demonstrate that events consistent with repeated chloroplast capture have shaped the reticulate evolutionary history of the clade, especially among African polyploid and Pan-American diploid lineages.

Phylogeny↗

PubMed2026

Impact of kangaroo care on circadian rhythm, growth, physiological stability in premature infants, and cortisol and melatonin levels in maternal breast milk: A randomized controlled trial.

PURPOSE: This study aimed to examine the effects of regular kangaroo care (KC) on sleep-wake cycles, growth, physiological stability, and maternal breast milk cortisol and melatonin levels in premature infants. DESIGN: This study was a parallel group, single-blind, pre-test-post-test, randomised controlled trial (RCT). METHODS: This randomized controlled study was conducted in a neonatal intensive care unit (NICU) in Türkiye between September 2024 and September 2025 Thirty-six premature infants were randomized to intervention (n = 28) or control (n = 28). Infants in the intervention group received KC for three consecutive days, twice daily (10:00 a.m. and 10:00 p.m.) for 60 min per session. Data were collected using the Infant Information Form, Physiological Parameters Monitoring Chart, and Premature Infant Sleep-Wake Cycles Tracking Chart. Sleep-wake cycles were monitored using a Bispectral Index device. Breast milk cortisol and melatonin levels were measured at baseline and on day three using the competitive ELISA method. The study was registered at ClinicalTrials.gov (NCT06589349). RESULTS: Regular KC had a statistically significant effect on BIS values, heart rate, respiratory rate, oxygen saturation, and body temperature (p < 0.05). No statistically significant effects were observed on infant body weight or on maternal breast milk cortisol and melatonin levels (p > 0.05). CONCLUSION: The findings indicate that regular KC is associated with improved regulation of the sleep-wake cycle and enhanced physiological stability in premature infants. No significant changes were observed in maternal breast milk cortisol or melatonin levels following KC.

Humans↗

PubMed2026

Littoral and wetland vegetation decrease carbon emissions from dry inland waters.

Lakes are recognized as active components of the inland water carbon (C) cycle, as organic matter is processed by microbial respiration, inducing large carbon dioxide (CO2) and methane (CH4) emissions. In the context of long-lasting drought periods, large uncertainties remain about: (1) the influence of wet-dry cycle on CO2 and CH4 fluxes in littoral zones and lacustrine wetlands; and (2) the contribution of emergent vegetation to C fluxes in dry inland waters. At the water-land interface of two shallow lakes, this study focuses on CO2 and CH4 fluxes from vegetated and bare dry inland waters in relation to hydrological fluctuations. Three seasonal campaigns were conducted to measure daytime CO2 and CH4 fluxes in pelagic, littoral and wetland surface waters, as well as in temporarily air-exposed sediments, using floating and static chambers, respectively. Our results reveal that wet-dry cycle in the littoral zone and wetlands strongly influence gaseous C fluxes through contrasting patterns, especially in late summer, when the biological processes are most active (primary production and respiration). In air-exposed littoral zones, organic-poor sandy sediments presented the lowest CO2 and CH4 emissions, whereas in air-exposed lacustrine wetlands, water-saturated sediments accumulated high amounts of plant-derived organic matter, promoting intense microbial activity and the highest C emissions. However, amphiphytes and helophytes vegetation in exposed littoral zones and wetlands reversed the direction of C fluxes, inducing the highest CO2 uptake due to high photosynthesis rates. This study underlines the relevance of considering vegetation in dry inland waters, particularly in lacustrine littoral zones and wetlands, to obtain comprehensive lake C budgets, especially under climate change scenarios.

Wetlands↗

PubMed2026

Integrated proteomic and acetylomic analyses reveal the metabolic reprogramming associated with increased tylosin-equivalent concentration in Streptomyces xinghaiensis sf106-B1.

Deciphering the metabolic basis of high-yield antibiotic production in Streptomyces is crucial for strain optimization. Atmospheric and room-temperature plasma (ARTP) mutagenesis of Streptomyces xinghaiensis sf106 generated a mutant with a 30% increase in tylosin-equivalent concentration (μg/mL). 4D-FastDIA quantitative proteomics identified 279 differentially abundant proteins enriched in the Type I polyketide synthase (PKS) pathway, with increased abundance of key macrolide-biosynthesis-related proteins. Lysine-acetylome profiling identified 1152 differentially abundant acetylation sites and revealed altered acetylation of enzymes involved in fatty acid metabolism and the tricarboxylic acid (TCA) cycle, suggesting adjustments in central metabolism associated with acyl-CoA precursor availability and energy generation. Integration of proteomic and acetylomic data suggests coordinated changes in protein abundance and lysine acetylation associated with the increased tylosin-equivalent concentration. These results highlight candidate nodes for rational metabolic engineering of S. xinghaiensis.

Streptomyces↗

PubMed2026

METTL14-mediated m6A modification of CCNE1 accelerates progression of myelodysplastic syndromes via MAPK-ERK and PI3K-AKT signaling pathways.

BACKGROUND: N6-methyladenosine (m6A) is the most common RNA modification and plays a key role in the initiation, progression, and relapse of multiple cancers, including hematologic malignancies. However, the role of m6A and m6A regulatory genes in myelodysplastic syndromes (MDS) remains unclear. This study aims to elucidate the function and molecular mechanism of methyltransferase METTL14 in MDS. METHODS: RT-qPCR was used to assess the expression of multiple m6A regulators, focusing on METTL14 in MDS patients and cell lines. METTL14 overexpressing and knockdown cell lines were established, and CCK-8, EdU, and flow cytometry assays were performed to explore the biological functions of METTL14.Dot blot, MeRIP-Seq, MeRIP-qPCR, RT-qPCR, and Western blot were employed to investigate the underlying molecular mechanism. RESULTS: Dysregulation of multiple m6A regulators was observed in MDS, among which METTL14 was upregulated. Elevated METTL14 expression increases MDS risk and adverse prognosis, emerging as a biomarker for poor prognosis. METTL14 promoted proliferation and cell-cycle progression of MDS cells while inhibiting apoptosis; corresponding changes were observed in cell cycle and apoptosis markers. METTL14 regulated cellular m6A levels. Downstream targets of METTL14 were enriched in cell cycle-related pathways, with CCNE1 identified as a critical target. Knockdown of METTL14, actinomycin D, or S-adenosylhomocysteine treatment reduced CCNE1 mRNA and protein levels. Furthermore, METTL14 activated MAPK-ERK and PI3K-AKT signaling via CCNE1 in an m6A-dependent manner, thereby promoting proliferative MDS cells' capacity. CONCLUSIONS: This study delineates a METTL14/m6A/CCNE1 signaling axis in MDS progression and suggests that METTL14-mediated m6A modification may be a potential therapeutic target for MDS.

Humans↗

PubMed2026

Long-term heat exposure reshapes muscle molecular regulation and enhances thermal tolerance in Clarias fuscus.

Rapid fluctuations in water temperature driven by global warming have become a major abiotic stressor affecting muscle function in teleost fish. This study examined the effects of long-term thermal conditions on heat tolerance in Clarias fuscus. Fish were maintained for 90 days at either a normal temperature group (NT, 26 °C) or a high-temperature group (HT, 34 °C). Subsequently, muscle histology, and transcriptomic profiles were observed following acute high-temperature exposure (34 °C) and after temperature recovery (26 °C). Histological analysis showed that fish from the NT under acute high-temperature stress exhibited severe muscle damage (atrophy, myofilament disruption, and myolysis), whereas fish from the HT displayed markedly reduced lesions. RNA-seq profiling revealed 5769 differentially expressed genes (DEGs) in the NT and 3292 DEGs in the HT following acute temperature challenges. Functional enrichment indicated that, in the HT, modulation of key cell cycle regulators (e.g., ccna, ccnb, cdk1, cdk2) contributed to alleviating muscle damage caused by temperature fluctuations. In the NT, genes associated with ribosome biogenesis (e.g., nop56, riok2, riok1) were up-regulated and then down-regulated during temperature fluctuation, whereas p53 in the cell cycle pathway showed the opposite expression pattern. These findings demonstrate long-term heat exposure reshapes molecular expression and regulatory mechanisms in the muscle of C. fuscus, thereby enhancing thermal tolerance and adaptability, and providing a theoretical basis for breeding heat-resistant, high-quality aquaculture strains.

Animals↗

PubMed2026

Comprehensive analysis suggests CRIF1 is a potential target in breast cancer associated with prognosis and immune infiltration.

BACKGROUND: CRIF1 is a multifunctional factor that regulates cell biological processes such as the cell cycle, cell proliferation, and energy metabolism, and it is a new molecule that contributes to the poor prognosis of many malignancies. However, its involvement in breast cancer development is not fully known. MATERIALS AND METHODS: To investigate the relationship between CRIF1 expression, prognosis, and clinical characteristics using The Cancer Genome Atlas (TCGA-BRCA). The relationship between CRIF1 expression and the immunological microenvironment was investigated using CIBERSORT, ESTIMATE. Breast tissue and CRIF1 expression were validated by IHC. A tiny interfering plasmid was designed to transiently transfect breast cancer cell lines, and proliferation-related functional tests were carried out. The effect of sh CRIF1 on tumor formation was confirmed using a subcutaneous tumor experiment in naked mice. RESULTS: We discovered that CRIF1 was highly elevated in breast cancer tissues and associated with a poor prognosis. CRIF1 stimulates breast cancer cell proliferation, migration, and invasion. Knockdown decreased PI3K/AKT/mTOR signaling, which boosted autophagy activity. Immune infiltration research revealed that patients with high CRIF1 expression had higher CD8+ T cell expression but reduced macrophage M2 expression. CONCLUSION: Upregulation of CRIF1 in breast cancer cells enhances malignant behavior, which may be mediated by PI3K/AKT/mTOR signaling and is linked to cellular autophagy.

Humans↗

PubMed2026

Antarctic Peninsula soil carbon stock and efflux: A complex interplay of soil properties and heavy metals.

This study establishes a quantitative framework for understanding surface soil carbon dynamics and ecosystem connectivity in Fildes Peninsula and Ardley Island, King George Island, South Shetland Islands, Antarctic Peninsula. The mean soil organic carbon (SOC) stock across all study sites was 1.10 ± 1.93 kg C/m². Restricting net carbon balance analysis to Fildes Peninsula, where soil respiration (Rs) data were available, yielded a site-specific SOC stock of 0.45 ± 0.45 kg C/m². Scaling Rs to a realistic 120-day active season and assuming stable SOC stocks resulted in estimated annual carbon loss of 15 g C/(m2·yr), equivalent to 3.3 % of standing SOC. Comprehensive sensitivity analyses spanning plausible winter respiration (0 %-20 % of summer rates) and annual change in SOC stocks (-1 %-2 %) consistently supported a net carbon sink, with turnover rates constrained to 3.3 %/yr-4.7 %/yr. Principal component analysis showed that ornithogenic processes as the dominant control on SOC, total nitrogen (TN), zinc (Zn), copper (Cu), and cadmium (Cd) provide a clear multivariate signature of marine-derived nutrient, while Pb was decoupled from this gradient and associated instead with fine-particle size controls. These results reveal dual but independent drivers of soil metal enrichment in this region. Despite their limited spatial extent, ornithogenic soils store disproportionately large carbon pools. Overall, this integrated analysis reveals how marine-terrestrial subsidies regulate Antarctic carbon cycling and provides a quantitative and reproducible framework for assessing carbon dynamics under ongoing climate change.

Antarctic Regions↗

PubMed2026

Prophylactic folinic acid prevents pemetrexed myelosuppression: A randomized trial toward safer treatment with chemotherapy in non-small cell lung cancer.

Background Pemetrexed is a cornerstone in advanced non-small cell lung cancer treatment. Although generally well tolerated, severe myelosuppression occurs in 26% of patients. Preventing chemotherapy-associated toxicity has become increasingly important with the introduction of osimertinib combined with pemetrexed-based chemotherapy. Due to substantial toxicity, this regimen is often not administered to frail patients. Folinic acid prophylaxis can mitigate pemetrexed-induced toxicity, however its preventive use has not been routinely studied. We aimed to investigate the efficacy of folinic acid prophylaxis to reduce myelosuppression. Methods Fifty patients treated with pemetrexed were randomized (1:1) to receive pemetrexed with or without oral folinic acid prophylaxis on days 2-4 after each chemotherapy cycle. The primary endpoint was absolute neutrophil count (ANC) after the first chemotherapy cycle. Secondary endpoints included ANC after the second cycle, grade neutropenia, treatment efficacy, renal function and incidence of dose modifications. Results Twenty-four patients received folinic acid and twenty-six served as controls. Higher ANC were observed in the folinic acid group after the first cycle (median 3.79; IQR 2.22-4.93 vs. 1.85; IQR 1.43-3.78; p.

Humans↗

PubMed2025

The molecular mechanism of cuproptosis and research progress in pancreatic diseases.

PURPOSE: Cuproptosis has been proven to be a novel mode of cell death, distinct from other types of cell death such as necrosis, ferroptosis, pyroptosis, and apoptosis. This study aims to systematically review the molecular mechanisms of cuproptosis in recent years and its research progress in pancreatic diseases. METHODS: By searching PubMed and Web of Science databases, 113 key literatures were included for thematic analysis, covering the molecular mechanism of cuproptosis and its role in the occurrence and development of pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cyst, pancreatic injury and pancreatic neuroendocrine tumor. RESULTS: Cuproptosis refers to the accumulation of copper ions in cells, which leads to instability of ferritin and aggregation of acylated proteins, resulting in oxidative stress-related cell death. Recent studies have shown that cuproptosis plays an important role in the occurrence and development of various pancreatic diseases, such as pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cysts, pancreatic injuries and pancreatic neuroendocrine tumor. The inducers of cuproptosis, such as disulfiram, chloroquinolones, and perilla phenols, alleviate pancreatic cancer by promoting cell cuproptosis. Copper chelators such as tetraethylenepentamine and tetrathiomolybdate promote the recovery of pancreatic injury by inhibiting cell cuproptosis. CONCLUSIONS: Cuproptosis plays a crucial role in the pathogenesis of pancreatic diseases. Further research on the cuproptosis pathway may become a potential target for the treatment of pancreatic diseases.

Animals↗

PubMed2026

Coordinated use of three homocysteine methyltransferases supports l-methionine biosynthesis and environmental adaptation among plant-associated bacteria.

Plant pathogens colonize multiple plant-associated habitats throughout their life cycle, encountering distinct nutrient conditions and microbial communities. l-methionine is required for bacterial growth and environmental adaptation. However, how plant pathogens coordinate l-methionine biosynthetic pathways to adapt to different plant-associated environments remains poorly understood. Here, using the plant pathogen Xanthomonas campestris pv. campestris strain XC1 as a model, we show that three homocysteine methyltransferase pathways allow XC1 to catalyze the final step of l-methionine biosynthesis using different methyl donors and cofactors under different environmental conditions. Bioinformatic and transcriptional analyses identified three homocysteine methyltransferase-associated operons in XC1, mesMXD, mmuPM, and metHRHaHb, corresponding to the MesD-, MmuM-, and MetHaHb-dependent pathways, respectively. MesD uses an endogenously synthesized methyl donor and functions as the dominant homocysteine methyltransferase under l-methionine-limiting conditions, supporting bacterial growth, intracellular l-methionine accumulation, and full virulence. Furthermore, MmuM enables XC1 to use plant-derived S-methylmethionine for l-methionine biosynthesis, whereas MetHaHb enables XC1 to use vitamin B12 supplied by a neighboring bacterium for l-methionine biosynthesis in co-culture. Expression analyses showed that mesMXD was the only homocysteine methyltransferase-associated operon that responded to l-methionine availability, and its expression also decreased when S-methylmethionine- or vitamin B12-dependent pathways supported l-methionine biosynthesis. Comparative genomic analysis further showed that the three-homocysteine methyltransferase configuration is conserved in Xanthomonas and is also present in other plant-associated bacteria. Together, these findings show that a plant pathogen can coordinate endogenous, plant-derived, and microbially supported homocysteine methyltransferase pathways to maintain l-methionine biosynthesis, providing a metabolic strategy for adaptation to plant-associated environments.

Methionine↗

PubMed2026

Resistance versus concurrent training with three assigned protein targets in middle-aged and older women: a randomized 2 × 3 factorial trial.

BACKGROUND: Evidence is limited regarding whether assigned protein targets modify responses to resistance training (RT) alone or to the same RT program plus cycling (concurrent training [CT]) in middle-aged and older women. This randomized 2 × 3 factorial trial examined bioelectrical impedance analysis (BIA)-derived skeletal muscle mass (SMM; primary outcome), other body composition outcomes, muscular and functional performance, and cycle-derived estimated VO₂max. METHODS: In this randomized 2 × 3 factorial trial, 108 women aged 40-77 years were assigned to 12 weeks of supervised RT or CT (identical RT followed by cycling) and protein targets of 0.8, 1.6, or 2.2 g·kg-1·d-1. Baseline-adjusted ANCOVA tested training × protein interactions and marginal training and protein effects. Complete-case analyses included 83 participants. RESULTS: For SMM, no training-condition × protein-target interaction (p = 0.856), marginal protein-target effect (p = 0.726), or marginal training-condition effect (p = 0.273) was detected. CT had a lower baseline-adjusted week-12 BFP than RT (adjusted difference, -2.04 percentage points; 95% CI, -2.94 to -1.14; p < 0.001). RT had a higher baseline-adjusted week-12 leg-press estimated 1-RM than CT (CT - RT: -6.68 kg; 95% CI, -8.32 to -5.04; p < 0.001), whereas CT had a higher baseline-adjusted week-12 cycle-derived estimated VO₂max (adjusted difference, 4.53 mL·kg-1·min-1; 95% CI, 3.80 to 5.25; p < 0.001). No detectable marginal protein-target effects or training-condition × protein-target interactions were observed for the key secondary outcomes. CONCLUSIONS: No detectable differences in SMM or key secondary outcomes were attributable to assigned protein target. Compared with RT, CT favored estimated aerobic fitness and BFP, whereas RT favored leg-press strength. Because CT included additional cycling and greater exercise exposure, these differences cannot be attributed solely to training modality. Null protein findings do not establish equivalence among doses.

Humans↗