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ER proteostasis failure in HYOU1 deficiency alters B cells, neutrophils, and interferon signalling.

Hypoxia upregulated 1 (HYOU1) is a stress-inducible ER chaperone. We investigated 2 unrelated patients carrying biallelic HYOU1 variants and presenting with primary immunodeficiency. Patient 1, homozygous for p.Pro444His, displayed failure to thrive, hypoglycemia, B cell lymphopenia, and neutropenia. Patient 2, compound heterozygous for p.Arg262Gln and p.Pro757_Glu758insAla, exhibited recurrent infections, enteropathy, and hypogammaglobulinemia. In Patient 1, while HYOU1 transcription was preserved, the protein was severely reduced. Tunicamycin treatment of dermal fibroblasts showed a blunted unfolded protein response and defective induction of ER stress-responsive genes. Immunophenotyping showed near-absence of circulating B cells, and single-cell RNA sequencing of bone marrow identified an arrest at the pro-B cell stage. Neutrophils displayed hypogranulation and dysregulated IFN- and apoptosis-associated transcriptional signatures, unresponsive to G-CSF. HYOU1 deficiency hence results in ER stress-induced proteostasis failure that simultaneously impairs adaptive immunity through B cell developmental arrest and innate immunity through neutrophil dysfunction and IFN pathway imbalance. This work expands the spectrum of HYOU1 deficiency and further identifies ER proteostasis as a central determinant of immune homeostasis.

Journal Article

Transcriptomic analysis reveals the molecular mechanisms underlying the inhibition of Mytilus edulis attachment by biofouling control agents.

This study combined acute toxicity assays, phenotypic quantification, and transcriptomic profiling to systematically investigate the inhibitory effects and molecular regulatory mechanisms of a novel alkylamine-based antifouling agent on survival, byssus secretion, and attachment behavior of juvenile Mytilus edulis. The 96 h-LC50 of the agent to juvenile M. edulis was 8.84 mg/L, and 10 mg/L of the agent completely inhibited mussel attachment within 24 h, significantly reducing byssal thread number, length, and diameter while increasing detachment frequency, resulting in irreversible attachment failure. Transcriptomic analysis identified 2746 differentially expressed genes, which were mainly enriched in pathways including signal transduction, immune defense, stress response, cytoskeleton organization, and protein binding. KEGG and GSEA enrichment revealed that the antifouling agent activated the MAPK stress signaling pathway, disturbed transcriptional regulation, and impaired intracellular homeostasis and cytoskeletal stability, thereby synergistically suppressing the expression of key byssal protein genes including mfp-1 and mfp-3 and ultimately blocking byssus synthesis and adhesion. This study clarifies the multi-pathway molecular mechanism underlying antifouling agent-induced attachment inhibition in M. edulis, and provides core molecular targets and theoretical support for developing efficient, specific antifouling activity, and potentially applicable marine antifouling technologies.

Animals

Biallelic Variants in ATP1A4 Are Associated with Oligoasthenoteratozoospermia and Male Infertility.

Male infertility, often caused by structural and functional sperm defects, remains genetically unexplained in a substantial proportion of cases. ATP1A4 encodes a testis-specific isoform of the Na+, K+-ATPase, a membrane enzyme crucial for maintaining cellular ionic homeostasis. Previous studies on Atp1a4 knockout mice have demonstrated severe defects in sperm motility and flagellar architecture; however, the contribution of ATP1A4 variants to human male reproduction remains to be elucidated. In this study, we identified compound biallelic variants in ATP1A4, a missense variant (c.2578 T>A, p.Tyr860Asn) and a frameshift variant (c.2582del, p.Gly861Aspfs*5), in a patient presenting with severe oligoasthenoteratozoospermia. Both variants markedly affected ATP1A4 protein expression. Morphological analyses revealed coiled and folded flagella, disrupted mitochondrial sheaths, and irregular head morphology in the patient's spermatozoa. Expression profiling revealed that ATP1A4 was highly enriched in post-meiotic spermatids and localized along the entire flagellum of mature sperm in both humans and mice, indicating a critical role in flagellar assembly and structural integrity. Notably, intracytoplasmic sperm injection (ICSI) in this patient resulted in low fertilization efficiency and failed implantation, suggesting a potential adverse impact of ATP1A4 deficiency on sperm functional competence beyond motility. These findings broaden the genetic spectrum of oligoasthenoteratozoospermia and highlight ATP1A4 as a potential gene associated with human male infertility.

Male

Maize ZmMYB59 inhibits post-germinative shoot and root elongation through ZmGA2ox3/10-mediated gibberellin catabolism.

Gibberellin (GA) promotes seed germination, but sustained or excessive GA signaling after germination can lead to aberrant root and shoot elongation. How GA homeostasis is transcriptionally restrained during post-germinative seedling development remains unclear. Using overexpression and gene-edited maize materials, we demonstrate that ZmMYB59 inhibits root and shoot elongation during post-germinative growth. Integrated RNA-Seq and CUT&Tag analyses identified the GA catabolism genes ZmGA2ox3 and ZmGA2ox10 as candidate direct targets of ZmMYB59. Hormone profiling analysis showed elevated bioactive GA1 and GA4 levels in the scutellum and aleurone layer cells of zmmyb59 mutants. Dual-luciferase assays, electrophoretic mobility shift assays, and ChIP-qPCR further confirmed that ZmMYB59 directly binds AC8 cis-elements in the ZmGA2ox3/10 promoters and activates their transcription. The zmga2ox3/10 double mutant, but neither single mutant, exhibited enhanced root and shoot elongation, accompanied by GA4 accumulation. This phenotype was suppressed by exogenous application of the GA biosynthesis inhibitor uniconazole. Transcriptomic and biochemical analyses further revealed enhanced starch degradation, reduced starch content, and increased soluble sugar accumulation in the double mutant. Taken together, these findings reveal that the ZmMYB59-ZmGA2ox3/10 module restrains GA accumulation and starch mobilization after germination, thereby coordinating reserve utilization with post-germinative root and shoot growth in maize.

Gibberellins

The HOXA gene cluster: a critical regulator in bone-related disorders.

BACKGROUND: Skeletal homeostasis relies on the dynamic balance between bone formation and bone resorption. The disruption of this balance acts as the central pathological mechanism of multiple metabolic bone diseases including osteoporosis, and is closely correlated with the progression of various other bone-related disorders. As pivotal transcription factors regulating embryonic development and cell fate, the homeobox A (HOXA) gene family plays an essential role in skeletal physiological and pathological processes. METHODS: This review systematically summarizes recent research advances of the HOXA gene family in bone-related diseases, concludes the evolutionarily conserved regulatory patterns of HOXA members, and clarifies the molecular mechanisms by which HOXA genes mediate bone metabolic disorders and the occurrence as well as development of bone diseases. RESULTS: Accumulating evidence demonstrates that HOXA family members present complex functions and strong heterogeneity in bone-related diseases. They participate in the pathogenesis of bone diseases via three evolutionarily conserved regulatory manners: determining regional patterning, modulating signaling pathways, and integrating epigenetic and non-coding RNA (ncRNA) regulatory networks. CONCLUSION: Further exploring the underlying mechanisms of the HOXA family in bone-related diseases provides novel insights into the pathogenesis of bone disorders. Meanwhile, it also supplies solid theoretical basis and potential therapeutic targets for the development of novel HOXA-targeted therapeutic strategies against bone diseases.

Humans

Structural and tissue-specific organisation of endocrine Fgf19 and Fgf21 signalling in rainbow trout.

Endocrine fibroblast growth factors (FGF19 subfamily) play a key role in regulating metabolic homeostasis in vertebrates. However, their functional diversification in salmonids remains poorly understood. In this study, we conducted an integrative characterisation of Fgf19 and Fgf21 signalling in rainbow trout (Oncorhynchus mykiss) by combining phylogenetic, structural and expression analyses. Phylogenetic analyses revealed the conservation of single fgf19 and fgf21 genes, despite the extensive expansion of receptors post-Ss4R (salmonid-specific fourth-round whole genome duplication). Structural modelling and molecular dynamics simulations demonstrated the stable interactions of both ligands to multiple Fgfr isoforms, with receptor-specific energetic profiles and conserved core interaction residues. Tissue expression profiling revealed clear differences from mammalian models, such as predominant hepatic fgf19 expression and the absence of hepatic fgf21 under basal conditions. In addition, there were complex and tissue-dependent distributions of fgfr and klotho transcripts. These findings support a receptor-driven diversification model of endocrine Fgf signalling in salmonids, suggesting enhanced endocrine plasticity associated with the retention of receptors following post-genomic duplication. Taken together, our findings provide new insights into the structural and regulatory organisation of endocrine Fgf signalling, as well as its potential role in metabolic regulation in rainbow trout.

Animals

Correlative analysis of endogenous miRNA expression profiles underlying brown planthopper adaptation to resistant rice.

The brown planthopper (Nilaparvata lugens Stål, BPH) is a major insect pest threatening global rice production. However, the molecular mechanisms underlying the adaptation of BPH populations with different virulence levels to resistant rice cultivars remain poorly understood. MicroRNAs (miRNAs), as key post-transcriptional regulators, play critical roles in host adaptation in herbivorous insects. In this study, we analyzed the miRNA expression profiles of a high-virulent population (IR56p) and a low-virulence population (TN1p) after feeding on susceptible (TN1) and resistant (IR56) rice cultivars. Our findings reveal distinct miRNA-mediated regulatory strategies employed by the two populations. The IR56p population showed downregulation of miRNAs including miR-10, miR-124, and miR-316, showing an inverse correlation with increased expression of predicted target genes involved in detoxification (carboxylesterase, UDP-glycosyltransferase) and effector function (calmodulin). In contrast, several miRNAs highly expressed in IR56p, including miR-307, miR-317, and miR-275, were predicted to target rice genes associated with hormone signaling, cell wall biosynthesis, and oxidative homeostasis, suggesting a possible but unproven inter-species regulatory role that requires functional validation. Collectively, these descriptive and correlative findings provide hypothesis generating insights into insect-plant coevolution and identifies candidate molecular targets for future functional validation and RNA interference-based pest management strategies.

Animals

The mighty microproteins: from versatile cellular regulators to precision medicine therapeutics.

Microproteins, are tiny proteins encoded by small open reading frame (sORF), translation of these non-canonical open reading frames (ncORFs) has been implicated in diverse biological processes and diseases. This review summarizes recent developments in the discovery, biogenesis, and functional characterization of microproteins, and their involvement in various disease, with special focus on their roles in cancer, cardiovascular, metabolic, neurodegenerative and immune-related disorders. We emphasize the regulation of key cellular pathways by microproteins, including mitochondrial homeostasis, apoptosis, metabolic reprogramming, and immune signaling, all of which affect disease initiation and progression. Emerging evidence also supports their potential as disease biomarkers and therapeutic candidates for precision medicine. Finally, the review critically discusses the current challenges including discrepancies in microprotein annotation, the limitations of ribosome profiling and proteogenomic approaches, the gap between computationally predicted and experimentally validated microproteins, and the need for rigorous orthogonal validation by means of CRISPR-based genome editing, ribosome release assays, mutational analysis, high-resolution mass spectrometry, and functional studies. Finally, we review recent development of AI-assisted ORF prediction, single-cell translatomics, spatial proteomics, and integrated multi-omics as emerging technologies reshaping. Microprotein discovery and functional annotation. Finally, we discuss the translational potential of microproteins and highlight the remaining challenges to clinical application, including peptide stability, pharmacokinetics, tissue-specific delivery, immunogenicity, and the need for rigorous preclinical and clinical validation. Together, this review provides an updated and critical overview of the rapidly evolving microprotein field and highlights future research priorities for translating these molecules into clinically useful biomarkers and precision therapeutics.

Microproteins

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

Inactivation of Aspergillus flavus spores by dielectric barrier discharge cold plasma: Kinetics, physiological properties and proteomic analysis.

A. flavus, as a pathogen, poses a grave threat to both human and livestock health, significantly influencing agricultural production as well. This study aimed to investigate the inactivation effect and mechanism of dielectric barrier discharge cold plasma (DBD-CP) on A. flavus spores. The results exhibited that DBD-CP effectively inactivated A. flavus spores by the Weibull + Tail model. Furthermore, the physiological and proteomic analysis revealed that DBD-CP destructed cell wall and membrane integrity, causing cellular protein leakage and increasing membrane penetration of ROS generated from DBD-CP. Although intracellular ROS was excessively accumulated, the protein levels and activities of SOD and CAT were decreased, indicating that intracellular redox homeostasis was disrupted by DBD-CP. Subsequently, DBD-CP treatment induced cellular protein oxidation and changed protein structures, resulting in unstable protein structures. Meanwhile, protein synthesis and degradation in A. flavus spores were disturbed by inhibiting ribosome biogenesis, initiation process and NEDD8-mediated UPS, which did not compensate for the loss of protein caused by oxidative damage and leakage, leading to A. flavus spore inactivation. Besides, DBD-CP could attenuate A. flavus virulence by downregulating hydrolytic enzymes and CFEM-related proteins. This study provides novel insight into the inactivation mechanism of DBD-CP against A. flavus spores, which establishes a basis for the application of DBD-CP in controlling pathogenic fungi contamination in grains and crops, promoting the development of DBD-CP in food and agricultural decontamination.

Spores, Fungal

Siglec-7 orchestrates mitochondrial dynamics and metabolic reprogramming to restrain human NK cell cytotoxic function.

Natural killer (NK) cells are innate lymphocytes that directly eliminate tumor and virus-infected cells by integrating signals from activating and inhibitory receptors, and their effector functions are tightly coupled to cellular metabolism. Given that the inhibitory receptor PD-1 reprograms T cell metabolism to shape functional fate, the bioenergetic consequences of inhibitory receptor engagement on human NK cells remain largely unexplored, particularly for sialic acid-binding immunoglobulin-like lectin (Siglec-7), a glyco-immune checkpoint receptor. Here, we investigated metabolic programs and effector functions associated with Siglec-7 expression and antibody-mediated Siglec-7 ligation in primary NK cells and NK-92MI cells. Siglec-7POS NK cells exhibited selectively impaired CD107a degranulation under glycolytic and oxidative phosphorylation inhibition, whereas Siglec-7NEG cells remained relatively resistant, indicating distinct energetic wiring between these subsets. Engagement of Siglec-7 by an agonistic antibody induced mitochondrial fission with altered Drp1 phosphorylation, transient mitochondrial depolarization, and broadly suppressed mitochondrial respiration, while concurrently enhancing glycolytic capacity, consistent with a dual metabolic shift upon Siglec-7 ligation. In contrast, sustained Siglec-7 expression in NK-92MI-S cells was associated with globally enhanced mitochondrial respiratory capacity, indicating that sustained Siglec-7 expression and short-term treatment with an agonistic anti-Siglec-7 antibody were associated with distinct metabolic profiles in NK cells. Furthermore, Siglec-7POS NK cells showed increased accumulation of autophagic vacuole, reduced proliferation, and heightened apoptotic susceptibility compared with Siglec-7NEG counterparts. Collectively, these findings support an association between Siglec-7 status, mitochondrial homeostasis, and metabolic fitness in NK cells, with Siglec-7NEG cells retaining a metabolically robust, cytotoxic phenotype.

Journal Article

Muscular fiber properties and multi-omics investigation of larval and adult locomotor muscle in Microhyla fissipes.

During metamorphosis, Microhyla fissipes undergoes a critical transition from an aquatic to a terrestrial lifestyle, accompanied by significant remodeling of skeletal muscle. Notably, larval tail muscle degenerates, while adult hindlimb muscle develops. However, the molecular mechanisms that orchestrate these muscle type-specific adaptations to the changing environment remain unclear. In this study, histological observation, transcriptomics, and metabolomics were integrated to compare locomotor muscles from two stages: larval muscle from tail versus adult muscle from hindlimb. Our results revealed that adult muscle fibers exhibited reduced diameter and shorter sarcomere length compared to those of tadpoles. Transcriptomic analysis identified 4103 differentially expressed genes (DEGs), including 2182 up-regulated and 1921 down-regulated genes. Up-regulated genes were mainly involved in energy metabolism and cellular homeostasis pathways, including PPAR signaling and oxidative phosphorylation, whereas down-regulated genes were associated with carbohydrate metabolism and cell proliferation pathways, such as glycolysis/gluconeogenesis and PI3K-Akt signaling. Metabolic profiling indicated a metabolic shift from anaerobic to aerobic energy production, with 57 differential metabolites identified, mainly involved in protein metabolism and insulin-related pathways. Integrated multi-omics analysis further highlighted the AMPK and FoxO signaling pathways play key roles in this process. In conclusion, our findings demonstrate that the metabolic and structural differences between larval and adult skeletal muscles are mediated by AMPK- and FoxO-dependent signaling pathways, providing novel insights into the molecular mechanisms underlying adaptive development and locomotor transition in anuran amphibians.

Animals

Metabolic depot for nucleated erythrocyte degradation: molecular and structural elucidation of the teleost melanomacrophage center.

The function of melanomacrophage centers (MMCs) has long been controversial. While their foundational function is widely accepted as "metabolic dumps" for waste processing, a widely circulated hypothesis posits that they are primitive germinal centers (GCs) executing adaptive immunity. To elucidate this controversy, this study systematically evaluated the splenic MMCs in a higher teleost ( Micropterus salmoides) by combining transmission electron microscopy (TEM) and high-resolution spatial transcriptomics. Structurally, TEM revealed that the MMC comprises a core with characteristic sparse cellular density, filled with cellular debris and encapsulated by a fibrous layer. Molecularly, under physiological conditions, MMC regions exhibited low transcriptional activity. We did not detect clear enrichment of B cell and T cell lineage genes, and the key GC marker aicda was not observed. Conversely, its predominant molecular signature was characterized by macrophage-driven iron metabolism (e.g., ferritin) and erythrocyte degradation (e.g., hba1). Furthermore, the physicochemical properties of MMCs pigments (e.g., argyrophilia) suggest that traditional histological staining methods warrant cautious interpretation regarding potential non-specific signals. In conclusion, our findings characterize the MMC as a highly specialized metabolic processing and sequestration niche. This study provides new perspectives on the evolution of immune-metabolic homeostasis in poikilothermic vertebrates, advances comparative immunology, and offers a critical scientific reference for the accurate interpretation of MMCs as a biological indicator in pathology and ecotoxicology.

Animals

Development and validation of a comprehensive prognostic model for 28-day ICU mortality in non-traumatic subarachnoid hemorrhage: an analysis based on the MIMIC-IV database.

BACKGROUND: Due to the complex pathophysiology of non-traumatic subarachnoid hemorrhage (SAH), accurate risk prediction remains a challenge. Our aim is to develop and validate a comprehensive prognostic model that integrates demographic characteristics, vital signs, laboratory parameters, and more, to provide clinical decision-making support in real-world practice. METHODS: We conducted a retrospective cohort study of 785 Non-traumatic subarachnoid hemorrhage patients. The cohort was randomly divided into a training set (n = 549) and a validation set (n = 236). Feature selection was performed using LASSO regression, followed by backward stepwise Cox regression for optimization. A nomogram was constructed based on independent predictive factors, and model performance was assessed using discrimination, calibration, and decision curve analysis. To prevent immortal-time bias, all predictors were anchored to a fixed early (first-24-hour) measurement window, treatment variables were modelled as binary indicators rather than cumulative exposures, and a five-model sensitivity analysis with baseline-severity adjustment was performed. RESULTS: The development of our model followed a systematic approach: first, 15 potential predictive factors were selected via LASSO regression, which were then refined to 12 independent predictors using backward stepwise Cox regression. The final predictive factors included: Ventilation, AHT, Nimodipine 60 mg, Age, SAPS.II, Input amount, Calcium total, Platelet count, White blood cells, Anion gap, pH, and Chloride. The integrated model demonstrated excellent predictive ability for 7-day, 14-day, and 21-day mortality in both the training set (AUC: 0.972, 0.934, 0.898) and the validation set (AUC: 0.968, 0.948, 0.911). Calibration curves and decision curve analysis confirmed the model's reliability and clinical utility across different time points. We constructed a nomogram for individualized risk prediction. Univariate Kaplan-Meier survival analysis demonstrated significant stratification of survival outcomes by each predictor, while restricted cubic spline analysis revealed non-linear relationships between continuous variables and mortality risk. Random survival forest analysis identified the top three predictive factors (Nimodipine 60 mg, Ventilation, AHT) and compared them with our full 12-variable model, confirming superior performance of the integrated model at all time points. At the 28-day primary endpoint, the model achieved a time-dependent AUC of 0.898 (training) and 0.904 (validation); after restricting predictors to the early baseline window, the leakage-controlled model retained good discrimination (validation C-index 0.803). CONCLUSIONS: Our ICU 28-day mortality prognosis model demonstrated robust performance in predicting ICU 28-day mortality in non-traumatic subarachnoid hemorrhage. The model, through the nomogram, provides individualized risk assessment, aiding clinical decision-making and patient stratification.

Humans

Genome-wide identification of the HSP70 superfamily in tropical sea cucumber Stichopus monotuberculatus and their expression analysis under low-salinity stress.

Heat shock proteins (HSPs) are a group of evolutionarily conserved molecular chaperones that serve as indispensable core regulators in preserving cellular homeostasis and orchestrating organismal stress responses. The tropical sea cucumber Stichopus monotuberculatus, a high-value aquaculture species, is sensitive to fluctuations in environmental salinity-a challenge that has emerged as a critical bottleneck limiting its large-scale commercial cultivation. However, no systematic investigation has been conducted to characterize the HSP70 superfamily in S. monotuberculatus and elucidate its functional roles in salinity adaptation. In the present study, we performed a comprehensive genome-wide scan and identified 19 HSP70 superfamily genes in the S. monotuberculatus genome, with the HSP70IV subfamily showing remarkable gene expansion, containing 8 distinct copies. Phylogenetic analysis, conserved motif identification, and gene structure characterization demonstrated high evolutionary conservation within each HSP subfamily. These genes were unevenly distributed across the chromosomes of S. monotuberculatus, and prediction of cis-acting elements revealed that their upstream regulatory regions were enriched with numerous functional elements associated with stress response and immune regulation. Salinity stress experiments revealed that under severe low-salinity conditions (18‰), the expression levels of SmHSPA14L and multiple HSP70IV subfamily members were significantly elevated, while SmHYOU1D was significantly downregulated; in contrast, only subtle changes were detected in the expression of most HSP70 genes under moderate low-salinity stress (24‰). These findings strongly suggest that HSP70 genes, particularly the expanded HSP70IV subfamily, may act as key modulators in the low-salinity stress response. This work provides valuable insight into the molecular mechanisms underlying salinity adaptation in tropical sea cucumbers.

Animals

From premature adrenarche to adult metabolic risk and hyperandrogenism: a systematic review and meta-analysis.

CONTEXT: Idiopathic premature adrenarche (IPA) has been associated with a higher risk of metabolic and reproductive dysfunction, but long-term/adult outcomes remain incompletely known. OBJECTIVE: To assess the relationship between IPA and metabolic syndrome, as well as polycystic ovarian syndrome, in premenarcheal adolescent and adult women. METHODS: We conducted a systematic review and meta-analysis of observational studies reporting outcomes in females with IPA after menarche. Databases were searched through February 2025. Primary outcomes included body mass index (BMI), insulin resistance markers, and clinical and biochemical markers of hyperandrogenism. Data were pooled using random-effects models. The GRADE approach was applied to assess the certainty of evidence. RESULTS: A total of 21 studies comprising 635 females with IPA and 307 age-matched controls were included. Compared to controls, IPA individuals showed significantly higher BMI (mean difference: 1.4; CI: 1.0-1.9), fasting insulin, and homeostasis model assessment of insulin resistance, indicating persistent insulin resistance. Markers of hyperandrogenism, including Ferriman-Gallwey score, dehydroepiandrosterone sulfate, and Free androgenic index, were also elevated. Secondary analyses revealed higher triglycerides, lower high-density lipoprotein, increased leptin, and greater carotid intima-media thickness, supporting an early pattern of cardiometabolic risk. GRADE assessment rated most outcomes as low certainty. CONCLUSION: Women with a history of IPA are at increased risk of long-term insulin resistance and hyperandrogenism, with early signs of adverse cardiometabolic profiles. These findings support the need for long-term monitoring in this population.

Humans

Desert-derived Ensifer sp. SA403 enhances potato salt tolerance by reshaping rhizosphere microbiome functions and host responses.

Soil salinization increasingly threatens global food security, and potato (Solanum tuberosum L.), a moderately salt-sensitive crop, is particularly vulnerable to saline soils. Plant growth-promoting rhizobacteria (PGPR) offer a promising strategy to improve crop performance, yet how PGPR interact with native microorganisms to enhance potato salt tolerance remains poorly understood. In this study, we identified a desert-derived PGPR strain, Ensifer sp. SA403, which substantially enhanced potato performance under high salinity across sterile, non-sterile and field conditions. Physiologically, inoculation with SA403 reduced shoot Na⁺ accumulation and increased the K⁺/Na⁺ ratio; notably, these effects were markedly stronger in non-sterile substrates than under sterile conditions, indicating that SA403-mediated ion homeostasis relies on cooperation with the resident microbiota rather than on the strain acting alone. Metagenomic profiling indicated that SA403 strain reshaped rhizosphere communities, significantly enriching beneficial taxa such as Priestia and Bradyrhizobium, and upregulated functional pathways involved in glutathione and sulfur metabolism. Furthermore, host transcriptomic analyses showed that SA403 modulated plant responses to salt stress, with differentially expressed genes enriched in jasmonic acid signaling, ethanolamine metabolism and amino-acid biosynthesis pathways. Field trials on saline soils confirmed that SA403 significantly increased seedling emergence and tuber weight. Together, our results demonstrate that SA403 functions as a biological mediator that optimizes rhizosphere microecology and coordinates ion balance and host signaling to enhance potato salt tolerance. These findings support the potential of SA403 as a robust PGPR-based tool for sustainable potato production on saline soils.

Rhizosphere

Multi-omics analysis reveals stage-associated differences in gut immunity and microbiota between juvenile and adult common carp (Cyprinus carpio).

In vertebrates, the development of intestinal immunity is closely associated with dynamic changes in the gut microbiota. However, stage-associated differences in intestinal immunity and gut microbial communities remain poorly characterized in teleost fish. In this study, transcriptomic analysis combined with 16S rRNA gene sequencing was employed to characterize intestinal immunity and gut microbial communities in juvenile and adult common carp (Cyprinus carpio). Transcriptomic profiling revealed marked developmental differences in intestinal immune function. Juvenile carp exhibited a predominantly innate immune phenotype, characterized by elevated expression of pro-inflammatory cytokines, antimicrobial peptides, and lysozyme-related genes. This immune profile was accompanied by enhanced mucosal barrier function and a relatively pro-inflammatory intestinal environment. In contrast, adult carp displayed increased expression of genes associated with adaptive immunity, suggesting that adult common carp exhibit relatively stronger adaptive immune characteristics than juvenile fish. Gut microbiota analysis demonstrated significant stage-dependent differences in microbial diversity and community composition. Juvenile fish were enriched with bacterial taxa potentially associated with innate immune activation, whereas adult fish harbored distinct microbial communities linked to intestinal homeostasis and barrier maintenance. Furthermore, correlation analyses identified significant associations between specific microbial taxa and innate immune-related gene expression, suggesting a close association between gut microbiota composition and intestinal immune characteristics in juvenile and adult common carp. Collectively, these findings reveal stage-associated differences in intestinal immunity and gut microbial communities between juvenile and adult common carp, thereby providing insights into intestinal immune characteristics at different developmental stages in teleost fish.

Animals