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PubMed2026

The cold case of state transition 7 (stt7) mutants of Chlamydomonas reinhardtii, solved by whole-genome sequencing.

The process of State Transitions (ST) corresponds to an STT7 kinase-driven redistribution of the transmembrane LHCII antenna proteins between Photosystem II (PSII) and Photosystem I (PSI), which results from changes in their phosphorylation state. For the past two decades, two LHCII-kinase mutants, stt7-1 and stt7-9, have been instrumental in the study of STs in Chlamydomonas reinhardtii, the former being a null mutant for the kinase but quasi-sterile in crosses, while the latter, although fertile, has a leaky phenotype. Using long-read sequencing, this study further characterized the genetic lesions of the stt7 mutant strains through whole-genome reconstruction and de novo chromosome assembly. In addition, two new stt7 null mutants were generated, one derived by crosses from the original stt7-1 and one obtained by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9) technology. This work provides a comprehensive genomic characterization of the original stt7-1 null mutant, revealing extensive chromosomal rearrangements and high levels of aneuploidy, associated with increased cell size and meiotic dysfunction. Reassessment of their physiology and genetic backgrounds highlights the need for caution in interpreting genetic information. We thus produced more reliable null mutants for the LHCII-kinase, amenable to genetic crosses for the study of STs in a variety of genetic backgrounds.

Chlamydomonas reinhardtii↗
PubMed2026

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↗
PubMed2026

Epigenetics and In Silico Transcriptome Analysis of Pediatric Acute Myeloid Leukemia.

Pediatric acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy that accounts for about 15%-20% of childhood leukemias. Despite therapeutic advances, relapses remain common, and survival for high-risk patients is below 60%. Unlike adult AML, pediatric AML displays distinct genetic mutations, including FLT3-ITD, NPM1, KMT2A rearrangements, and core-binding factors (CBF) fusions, as well as extensive epigenetic dysregulation. Aberrant DNA methylation, histone modifications, and altered non-coding RNA expressions disrupt hematopoietic differentiation and activate oncogenic transcriptional networks. Recent advances in silico transcriptomic analysis have transformed the study of pediatric AML by integrating gene expression and epigenetic data to identify molecular drivers and regulatory networks. Computational RNA-seq pipelines and pathway analyses have highlighted key epigenetic regulators, including DNMT3A, TET2, and HDACs, as potential therapeutic targets. Multi-omics approaches combining transcriptomic, methylomic, and chromatin accessibility data are increasingly used to define biomarkers for diagnosis, prognosis, and therapeutic response. This review provides a comprehensive overview of the molecular and epigenetic landscape of pediatric AML, emphasizing the power of in silico transcriptome analysis to uncover disease mechanisms, refine patient stratification, and guide the development of precision-based epigenetic therapies aimed at improving long-term outcomes in children with AML.

Humans↗
PubMed2026

Prevalence of Theileria luwenshuni in goats (Capra hircus) on Tarama Island, Okinawa, Japan.

Caprine theileriosis is an economically important tick-borne disease caused by various Theileria species, particularly Theileria lestoquardi, Theileria luwenshuni, and Theileria uilenbergi, in goats (Capra hircus). Goat farming plays an economically and culturally important role on Tarama Island, Okinawa, Japan. Because goats on the island are mainly managed under an extensive grazing system, tick infestation is common. However, Theileria infections have not previously been investigated in goats on Tarama Island. To address this, archived DNA samples prepared from blood collected from 44 goats on Tarama Island were screened using a universal PCR assay targeting 18S rRNA sequences of Theileria and Babesia species. Two DNA samples were positive, and sequencing analysis of the amplicons identified T. luwenshuni. To further investigate the epidemiology of T. luwenshuni on Tarama Island, blood samples were subsequently collected from 96 goats across 19 farms. From each blood sample, a thin blood smear was prepared and genomic DNA was extracted. Microscopic examination of Diff-Quik-stained smears detected intraerythrocytic Theileria-like organisms in 35 (36.5%) goats. In addition, screening of DNA samples using a newly developed T. luwenshuni-specific PCR assay detected 77 (80.2%) positive goats, and the subsequent sequencing analysis confirmed the PCR results. Given that T. luwenshuni can cause severe disease in small ruminants, our findings highlight the importance of managing T. luwenshuni infection in goats on Tarama Island.

Animals↗
PubMed2026

A mechanism-guided framework for prioritizing membrane-interaction anti-Vibrio peptides from peptidomics data.

A mechanism-guided framework for prioritizing membrane-interaction antimicrobial peptide candidates from proteomics-derived peptide mixtures is presented. The framework integrates conservative machine-learning-based antimicrobial peptide (AMP) screening with a literature-derived membrane-interaction plausibility (MAP) assessment and a data-driven membrane-interaction ranking function (AIPx), followed by structural visualization for interpretability. MAP encodes physicochemical characteristics commonly associated with peptide-membrane interaction and provides a graded plausibility assessment. Building upon this physicochemically interpretable framework, AIPx ranks peptides using feature weights calibrated from experimentally characterized anti-Vibrio peptides, where minimum inhibitory concentration (MIC) values are used as a coarse-grained ranking reference rather than a direct prediction target. In a peptidomics-based peptide fractionation study targeting Vibrio spp., AIPx exhibited a consistent relationship with experimentally observed antibacterial activity. Distributional analysis revealed that peptide fractions exhibiting high anti-Vibrio activity are characterized by enrichment of high-ranking peptides rather than by AMP abundance alone. By structuring AMP identification and prioritization as sequential stages, the MAP + AIPx framework enables interpretable and experimentally actionable candidate selection by reducing biologically implausible candidates. The framework facilitates species-oriented prioritization of AMP candidates, addressing a key challenge in antimicrobial peptide discovery where activity may depend on target-specific membrane characteristics. Moreover, the approach is extensible through species-specific calibration and supports interpretable, mechanism-informed prioritization in antimicrobial peptide discovery.

Proteomics↗
PubMed2026

Microbial diversity, functional activities, and safety risks in fermented tea: a comprehensive review.

Microbial fermented teas are gaining global popularity due to their unique sensory profiles and health benefits. The quality and safety of these products are governed by complex microbial ecosystems that orchestrate the biotransformation of tea leaf components. This review addresses a critical paradox in the field: the same microbial activities that generate desirable bioactive metabolites, such as theabrownins and organic acids, also create ecological niches for mycotoxigenic fungi, posing significant health risks from contaminants like ochratoxin A, citrinin, and aflatoxins. While extensive research has cataloged the microbial diversity in these systems, a comprehensive framework linking processing environments to microbial community assembly, functional outcomes, and quantifiable safety risks remains elusive. This review systematically bridges this gap by synthesizing current knowledge on the microbial consortia-dominated by Aspergillus, Penicillium, Bacillus, and Lactiplantibacillus species-that drive tea fermentation. We critically analyze their functional roles in enhancing flavor, bioactivity, and potential probiotic activity while simultaneously evaluating the mechanisms of mycotoxin production and accumulation. By integrating microbial ecology, biochemistry, and food safety, we propose a forward-looking perspective focused on transitioning the industry from traditional, spontaneous fermentation to modern, controlled biotechnological processes. This approach, centered on the use of defined starter cultures, predictive modeling, and active biocontrol strategies, provides a roadmap for ensuring the consistent quality and safety of fermented tea products, ultimately unlocking their full potential as high-quality functional foods.

Tea↗
PubMed2026

Biochemical Insights Into the Conserved Interactions of NMD Factors From Budding Yeast to Humans.

Nonsense-mediated mRNA decay (NMD) is one of the most extensively studied pathways of cytoplasmic mRNA degradation. It plays a critical role in diverse cellular processes by eliminating aberrant transcripts containing premature stop codons and by regulating the stability of physiological mRNAs. NMD factors were initially identified through genetic screens in S. cerevisiae (UPF1, 2, 3) and C. elegans (SMG-1, SMG5-7). Subsequent biochemical and genetic studies revealed the composition of NMD complexes and identified additional factors. A major protein hub for NMD is Upf1, an ATP-dependent RNA helicase that is part of two mutually exclusive NMD assemblies, the Upf1-Upf2-Upf3 complex and the Upf1-decapping complex, which contains the decapping enzyme and its co-factors. Here, we discuss recent findings, primarily from budding yeast, on the protein-protein interactions driving NMD complexes dynamics and their similarities to human NMD. Together, the N-terminal cysteine and histidine rich (CH) and helicase domains (HD) of Upf1 act as a hub for binding multiple partners. Upf1 is required for binding to NMD substrates and for the initiation of RNA degradation through decapping (yeast) or endonucleolytic hydrolysis (humans). We focus on the interplay between Upf2, Dcp2 and Nmd4 (yeast SMG6), which ensures the mutually exclusive formation of Upf1-bound subcomplexes modulating Upf1's affinity for RNA. Thus, the study of NMD factors interactions in different organisms sheds new light on the remarkable conservation of NMD molecular mechanisms.

Nonsense Mediated mRNA Decay↗
PubMed2026

Webcam-Based Real-Time Visual Feedback During Baduanjin Practice in Older Adults: 6-Week Pilot Randomized Study.

BACKGROUND: Baduanjin qigong is a traditional mind-body exercise used to support balance and physical health in older adults. Age-related changes in proprioception may make accurate self-directed performance difficult without external guidance. OBJECTIVE: The aim of this study is to explore whether webcam-based real-time visual feedback delivered during supervised laboratory sessions was associated with differences in webcam-derived 2D pose discrepancy and movement consistency during Baduanjin practice in older adults. METHODS: A total of 31 older adults were enrolled, and 28 participants with complete analyzable records were included in this complete-case dataset (feedback group, n=14; nonfeedback group, n=14). All sessions were conducted face-to-face in a supervised motion-analysis laboratory. Weekly 2D pose-discrepancy values were analyzed using a linear mixed-effects model with fixed effects for group, categorical week, and the group-by-week interaction and a participant-specific random intercept. Joint- and movement-specific participant-level 6-week means were analyzed exploratorily using Welch independent-samples t tests. Holm correction was applied across 24 exploratory contrasts (6 week-specific, 8 joint-specific, and 10 movement-specific comparisons), and Hedges g and 95% CIs were reported. Participant-specific weekly slopes and within-participant variability were additionally examined to directly assess longitudinal error drift. RESULTS: The linear mixed-effects model showed no significant group-by-week interaction (Wald χ25=1.09; P=.96) and no significant overall week effect (Wald χ25=6.40; P=.27). Averaged across 6 weeks, the feedback group had an estimated mean 2D pose discrepancy 1.20° lower than the nonfeedback group (95% CI -2.38° to -0.02°; P=.046), although this marginal pilot finding was sensitive to an analytic approach. No week-specific contrast remained significant after Holm adjustment. Nominal right elbow, right shoulder, and right knee differences did not survive global Holm correction. Form 3 showed a lower mean discrepancy in the feedback group (mean difference -3.70°, 95% CI -5.86° to -1.54°; Hedges g=-1.30; unadjusted P=.002; Holm-adjusted P=.04). Direct analyses of participant-specific slopes and within-participant SDs did not support a significant between-group difference in longitudinal error drift. CONCLUSIONS: In this small exploratory pilot study conducted under supervised laboratory conditions, the 6-week trajectories did not differ significantly between groups. A marginally lower average 2D pose discrepancy was observed in the feedback group across the 6 weeks, but no individual week- or joint-specific comparison remained significant after multiplicity adjustment. Form 3 was the only exploratory contrast that remained significant after global Holm correction. Direct longitudinal analyses did not demonstrate prevention of error drift. Larger studies using validated reference measurements, prespecified outcomes, and adequately powered longitudinal designs are required.

Humans↗
PubMed2026

Transcriptome analysis of the pectoral fin degeneration in half-smooth tongue sole (Cynoglossus semilaevis).

Appendage degeneration is a notable morphological feature of some teleosts with specialized benthic lifestyles. The half-smooth tongue sole (Cynoglossus semilaevis) undergoes severe pectoral fin regression during metamorphosis. However, the molecular basis underlying rapid pectoral fin degeneration remains unclear. Here, we performed time-series transcriptome sequencing on pectoral fins at pre-metamorphosis, metamorphosis peak and post-metamorphosis to characterize the molecular changes associated with pectoral fin degeneration. Transcriptional dynamics and functional enrichment showed that no significant enrichment of classical apoptosis-related transcriptional pathways was detected during pectoral fin degeneration. Instead, sustained downregulation of twist1b, identified as a transcriptomic candidate, together with significant upregulation of ssh1, coupled with enrichment of lysosome and ubiquitin-proteasome system (UPS) pathways, suggested enhanced tissue remodeling during pectoral fin degeneration. Temporal expression clustering revealed heterochronic misalignment in the developmental gene expression: upstream initiator tbx5 was upregulated at early metamorphosis, while downstream maintenance signal fgf10 decreased synchronously. Distal patterning gene hoxd12a exhibited premature expression and rapid decay, losing sustained late-phase expression. Moreover, transient elevation of gli3 during metamorphosis may contribute to restricted distal fin growth. We conclude that pectoral fin degeneration in C. semilaevis is associated with heterochronic disruption of developmental signaling and extensive tissue remodeling. This study provides transcriptomic insights into pectoral fin degeneration in tongue soles and establishes a basis for future functional studies of appendage reduction in teleosts.

Animals↗
PubMed2026

Divergent trajectories of genome architecture and chromosome evolution in ferns and angiosperms.

Ferns and angiosperms represent the two largest vascular plant lineages but exhibit striking genomic and ecological contrasts. We investigated whether differences in genome size, chromosome architecture, GC content, and stomatal traits reveal divergent evolutionary trajectories between these lineages. We assembled the most comprehensive dataset to date, integrating genome size, chromosome number and size, GC content, and stomatal traits for over 1100 fern species and compared it with an extensive angiosperm dataset. Ferns exhibited markedly lower variability and c. 16-fold slower rates of chromosome size evolution than angiosperms. A persistent positive relationship between genome size and chromosome number in ferns suggests limited cytological post-polyploid diploidization. While ferns generally possess larger stomata, this difference disappears after accounting for genome size, indicating that nucleotypic constraints, rather than lineage-specific physiology, dictate stomatal dimensions. Both groups share a unimodal GC-genome size relationship peaking at c. 14 Gbp. Larger fern chromosomes imply lower genome-wide recombination rates, potentially limiting genetic reshuffling and adaptive potential. Our results highlight fundamentally divergent evolutionary trajectories, likely shaped by meiotic symmetry in ferns and meiotic asymmetry, possibly centromere drive, and post-polyploid diploidization in angiosperms, defining the functional and genomic landscapes of these lineages across deep evolutionary timescales.

Genome, Plant↗
PubMed2026

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↗
PubMed2026

Penalized Cumulative Probability Model for a Continuous Outcome Subject to Detection Limits.

Mixed-type outcome data occur when the outcome variable's distribution is a mixture of both continuous and discrete ordinal variables. Such mixed-type outcomes are common in biomedical, psychological, and the health sciences, particularly for variables having either a detection or quantitation limit. When interest lies in identifying a combination of genomic features associated with a mixed-type outcome, any method used would require a variable selection strategy for high-dimensional data. Unfortunately, few variable selection methods exist for modeling a mixed-type outcome when the covariate space is high dimensional. This study develops a high-dimensional penalized cumulative probability model (CPM), to allow for the identification of genomic features associated with mixed-type outcome of interest. We demonstrated how such model may be estimated using the iterative penalization procedure-the generalized monotone incremental forward stagewise (GMIFS) algorithm. The Model-X knockoffs procedure was combined with the estimation algorithm to control the false discovery rates (FDR) when performing variable selection. Through extensive simulation studies, our penalized CPM was shown to outperform alternative methods in terms of controlled variable selection performance by achieving high statistical power with the FDR being controlled at the target level. We demonstrate the utility of our method by applying it to predict estimated glomeruli filtration rate (eGFR) in kidney transplant recipients at 24 months post-transplant using baseline gene expression data as predictors. Our CPM model identified five genes associated with this mixed-type outcome which have important links to renal disease, which may provide prognostic guidance for kidney transplantation recipients.

Models, Statistical↗
PubMed2026

Is There a Difference in Occurrence of Complications Between Adults With Hemoglobin SS and Hemoglobin SC Disease: An Extended Systematic Review.

Sickle cell disease (SCD) is characterized by both acute and chronic complications. The clinical manifestation of these complications differs between genotypes. Given the large amount of research already published, this systematic review aims to offer a complete overview of types of sickle cell complications between adults in the most common genotypes Hemoglobin SS (HbSS) and Hemoglobin SC (HbSC), putting options for further research into perspective. An extensive literature search was performed to study all available evidence on these complications. This review was performed according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) statement guidelines, and was performed on January 2, 2024. A total of 710 references were identified. After careful screening, 521 records were excluded based on title and abstract and other exclusion criteria. In total, 158 articles were excluded after full-text assessment. Our analysis of 31 studies highlights key differences in complications between HbSS and HbSC genotypes in sickle cell disease (SCD). Vaso-occlusive crises (VOCs) remain the most common acute complication in both genotypes. HbSS patients experience more frequent VOCs, while HbSC patients generally have a milder clinical course when it comes to acute complications. Chronic complications, particularly in the ocular and pulmonary systems, are more prevalent in HbSC patients. However, as acute complications are more common in HbSS and chronic complications more common in HbSC, both genotypes face progressive organ damage due to recurrent ischemic injury and inflammation.

Humans↗
PubMed2026

Imaging techniques for assessing the hand in systemic sclerosis: a systematic review.

BACKGROUND: Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease frequently associated with hand involvement, leading to significant functional impairment. Imaging techniques provide unique opportunities to visualize and quantify structural and functional abnormalities of the hand, supporting diagnosis, monitoring, and treatment evaluation. This systematic review summarizes the imaging techniques used in SSc. METHODS: A systematic search of PubMed and Embase was conducted. Eligible studies included original research articles in English that applied or evaluated imaging techniques of the hands in SSc, published after 2000. Ultrasound and nailfold capillaroscopy were excluded, given their established use. Screening was performed independently by two authors. Findings were synthesized by clinical manifestations, study quality was assessed using the QUADAS-2 tool. RESULTS: Sixty-one studies met the inclusion criteria. In total, 25 distinct imaging techniques were identified, enabling assessment of various hand structures, including vascular involvement, inflammation, fibrosis, calcifications, erosions, and bone marrow edema. Vascular imaging was most extensively studied, particularly in the context of Raynaud's phenomenon and digital ischemia, with multiple techniques demonstrating impaired perfusion and altered thermoregulatory responses. MRI consistently detected subclinical inflammatory and erosive changes of joints and soft tissues,. CT-based techniques provided detailed assessment of calcinosis cutis, while optical and photoacoustic methods showed promise for quantifying skin fibrosis. CONCLUSION: Imaging techniques provide valuable, complementary insights into hand involvement in SSc, often revealing subclinical disease. Despite promising results, limited standardization and longitudinal validation currently restrict clinical implementation. Future studies should focus on harmonizing protocols and validating against clinically meaningful outcomes.

Humans↗
PubMed2026

Measurable Residual Disease and the Unresolved Biology of Leukemic Stem Cells.

Measurable residual disease (MRD) testing has transformed the management of hematologic cancers by enabling detection of residual malignant cells after therapy. Current approaches rely on qPCR and next-generation sequencing to monitor leukemia-associated somatic mutations, while multiparameter flow cytometry identifies aberrant leukemic immunophenotypes. Although these methods provide valuable prognostic and therapeutic information, MRD negativity remains an imperfect surrogate for cure. Most MRD platforms evaluate CD45+, rapidly dividing leukemic populations and fail to detect quiescent cells that may survive cytotoxic therapies which efficiently target proliferating hematopoietic cells. Relapse frequently occurs despite deep molecular remission, suggesting persistence of rare leukemic stem cells (LSCs) that are intrinsically resistant to chemotherapy and targeted therapies. The paradox of relapse despite molecular remission could be explained by the presence of very small embryonic-like stem cells (VSELs) which are pluripotent, quiescent stem cells sitting at the top of cellular hierarchy in multiple adult tissues including bone marrow. A pluripotent VSEL divides through asymmetrical cell division to give rise to two cells of different sizes and fates, smaller cell is to self-renew while the bigger is lineage-restricted and tissue-committed progenitor which undergoes extensive epigenetic changes, divides rapidly and undergoes clonal expansion before further differentiation. Dysfunctions of VSELs initiate both solid and hematologic cancers. Based on this view, somatic mutations monitored during MRD assessment possibly represent downstream consequences of clonal expansion rather than the initiating drivers of disease persistence. Thus, exclusive monitoring of somatic mutations and CD45 + leukemic populations possibly overlook rare, small-sized, CD45- VSELs that contribute to therapeutic resistance and relapse.

Humans↗
PubMed2026

Cardiovascular Drug Access in Australia and New Zealand: New PBS and PHARMAC Listings, 2023-2025.

BACKGROUND: Cardiovascular disease is a leading cause of death in Australia and New Zealand. Publicly subsidised access to new cardiovascular medications is governed by the PBS (Pharmaceutical Benefits Scheme) in Australia and PHARMAC (Pharmaceutical Management Agency) in New Zealand, yet no consolidated resource catalogues recent listings across both jurisdictions. METHODS: We reviewed all new cardiovascular drug listings and indications on the PBS and PHARMAC schedules from 1 January 2023 to 31 December 2025. PBS data were obtained from the PBS Pricing and Policy Branch through the Cardiac Society for Australia and New Zealand. PHARMAC data were obtained via direct communication with PHARMAC and cross-referenced with public schedule information. Pivotal trial evidence, restriction criteria, and prescribing considerations were extracted from published literature and regulatory documents. RESULTS: Five new cardiovascular drugs were PBS-listed (inclisiran, mavacamten, tafamidis, icosapent ethyl and migalastat), two existing drugs received new cardiovascular indications (empagliflozin and dapagliflozin for heart failure with preserved ejection fraction) and prasugrel was relisted for acute coronary syndrome. One major change occurred on the PHARMAC schedule (empagliflozin for heart failure with reduced ejection fraction). CONCLUSIONS: The 2023-2025 period has seen notable additions to cardiovascular pharmacotherapy in Australia, including the first cardiac myosin inhibitor, the first transthyretin stabiliser, expanded lipid lowering therapy options, and extension of SGLT2 inhibitor coverage across the heart failure ejection fraction spectrum. A pronounced access disparity persists between Australia and New Zealand.

New Zealand↗
PubMed2026

Preregistration nursing student attrition and strategies to improve student retention in university; an umbrella review.

BACKGROUND: Attrition among preregistration nursing students remains a persistent international challenge, contributing to nursing workforce shortages. Although extensive research has examined factors influencing student attrition and retention, the evidence is fragmented across review-level literature, limiting clarity regarding priority and evidence-informed retention strategies. AIM: To synthesize review-level evidence on factors associated with preregistration nursing student attrition and to identify strategies that support student retention in university-based nursing programs. METHODS: An umbrella review was conducted in accordance with the Joanna Briggs Institute methodology. Six electronic databases were systematically searched for peer-reviewed literature reviews published in English between January 2016 and October 2025. Eligible reviews focused on undergraduate preregistration nursing students in face-to-face university programs. Methodological quality was appraised using the JBI critical appraisal checklist. Findings were synthesised using narrative and thematic approaches. RESULTS: Seventeen literature reviews were included. Attrition was consistently described as multifactorial, influenced by academic preparedness, psychosocial wellbeing, socio-demographic factors, and institutional support. Retention strategies reported across reviews were predominantly relational, developmental, and sustained over time, including mentoring, tutoring, academic skills development, psychosocial support, and interventions that foster belonging. Faculty engagement and holistic approaches were repeatedly associated with improved student persistence. However, the evidence base was largely descriptive, with limited experimental evaluation of intervention effectiveness. CONCLUSION: Preregistration nursing student retention is best supported through multifaceted, sustained strategies that begin at admission and extend throughout the curriculum. While current evidence highlights consistent patterns of effective support, further rigorous research is required to evaluate retention interventions and extend evidence to flexible nursing education pathways.

Humans↗
PubMed2026

Acetylcholine signaling regulates osmotic stress adaptation in the phytopathogen Dickeya solani.

Plants impose strong selective pressures that shape both the composition and functional potential of plant microbiomes. The adaptation of plant-associated bacteria to their hosts relies on an extensive repertoire of signal transduction systems that sense plant-derived molecules and dynamically adjust bacterial physiology and metabolism within the holobiont. These signals include key plant signaling compounds that regulate processes essential for plant-microbe interactions. Among them, acetylcholine is emerging as an important signaling molecule in both plants and bacteria. Here, we demonstrate that acetylcholine regulates the expression of the osmotic stress response betIBA gene cluster in the important phytopathogen Dickeya solani, where it plays an important role in osmoprotection. We show that the TetR-family transcriptional regulator associated with this pathway, BetIDs, recognizes acetylcholine as well as choline and trimethylamine. These three ligands differentially induce betIBA transcription in a manner that correlates with their binding affinities. Ligand binding does not affect BetIDs binding to the bet promoter or its oligomeric state. Instead, it induces pronounced changes in the secondary structure of BetIDs, with the magnitude of these conformational changes being ligand-dependent. We further show that quorum sensing modulates osmotic stress tolerance in D. solani by regulating the expression of the Bet pathway. The Bet system is required for the full virulence of D. solani, particularly in chemically complex plant tissues. Phylogenetic analyses reveal that the BetIBA system is widely distributed among plant-associated Pseudomonadota, collectively supporting its importance for bacterial survival and adaptation in plant-related environments.

Osmotic Pressure↗