Convergent evolution offers a unique lens through which to explore the molecular underpinnings of significant phenotypic transformations. Similar selective pressures likely drove the evolution of analogous milk traits in sheep and goats. Consequently, the current study aimed to identify common selection signals for milk traits across dairy and non-dairy breeds of sheep and goats worldwide. In this study, a total of 308 whole-genome sequences from diverse sheep (n = 108) and goat (n = 200) breeds, including both dairy and non-dairy types, across the world were utilized. The population structure and genetic diversity of dairy and non-dairy sheep and goat breeds were characterized. Species-specific genes associated with milk traits, such as POU2F1, ABCD2, TRNAC-GCA in sheep and PRPF6, VPS13C, TPD52L2, NFX1 and B4GALT1 in goats, were identified. Further gene annotation and bioinformatics analyses indicated that different biological pathways are important for milk traits in each species: fatty acid oxidation and AMP metabolic process in sheep, the U2-type spliceosomal complex and propanoate metabolism in goats. Additionally, common signatures of selection such as CLASP1, PDS5B, ZNF831, CCDC73 were found in sheep and goats. Haplotype and transcriptional analyses further confirmed the role of these genes in milk production and provided evidence for their analogous evolution in sheep and goats. The CLASP1 genewas identified as a target of convergent selection, representing a promising candidate for genetic improvement programs in dairy species. These results provide insights into the genetic basis of convergent dairy traits, offering valuable targets for improving milk production and advancing dairy sheep and goat breeding programs.

Abstract Vaccine hesitancy was a major concern during the Covid-19 pandemic, and a significant percentage of healthcare workers (HCWs) proved to be hesitant too. Various governments, including that of Greece, reacted aggressively, imposing mandates stipulating dismission of HCWs from work unless vaccinated. Hesitancy was understood as a case of moral failing and against the principle of ‘do no harm’. In this article, we deploy hermeneutics policy analysis based on interviews and analysis of texts to challenge this view. On the basis of qualitative analysis of transcripts of press conferences organized by the Greek Ministry of Health and 74 interviews with hesitant HCWs, we show that government’s and HCWs’ understanding of the risk of infection and the associated threat posed to the public health system were starkly different. For HCWs, hesitancy was linked to distrust toward political institutions, which should be treated in a different manner from a case of moral failing of HCWs. We argue that, rather than mandates, persuasion is a better strategy, since hesitancy raises the question of trust toward the politicoscientific establishment. Therefore, reforming science advice institutions so that they make use of local expertise and engage civil society is key. We focus on Greece, as we consider it to be an interesting case of a newly established science advice system with a distinctive character that we term the ‘look from inside’, based on the model of ‘ethical chief scientist,’ which makes it a brilliant case study for others considering building or reforming their systems.

Introduction Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive and debilitating disorder caused by excessive glucocorticoid exposure. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) and their exosome (Exos)-mediated signal transduction plays a key role in SONFH; however, the exact pathways involved remain under active investigation. Methods The differential expression profiles of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) related to the Exos-mediated pathway in Exos derived from human BMSCs (hBMSCs) of patients with SONFH and control patients were analyzed by next-generation sequencing (NGS). The miR‐199a‐3p was identified as a differentially expressed miRNA, and its expression in BMSCs and their corresponding Exos was subsequently validated using quantitative real-time polymerase chain reaction. A series of functional experiments then confirmed that miR-199a-3p modulated osteoblasts (OBs) and human umbilical vein endothelial cells (HUVECs) activities via the Exos-mediated pathway, including cell proliferation, apoptosis, osteogenesis, and angiogenesis, with or without exposure to high-dose dexamethasone (Dex). Results NGS results revealed a total of 6,953 differentially expressed ncRNAs, 260 differentially expressed miRNAs, 13,577 differentially expressed mRNAs were identified in hBMSCs from patients with SONFH compared to controls. In hBMSCs-Exos, 207 differentially expressed ncRNAs, 183 differentially expressed miRNAs, and 1,075 differentially expressed mRNAs were detected. Integrated analysis of transcripts expressed in both hBMSCs and hBMSCs-Exos identified 659 differentially expressed ncRNAs, 11 differentially expressed miRNAs, and 1,600 differentially expressed mRNAs. The results of bioinformatics analysis showed that these differentially expressed RNAs were involved in regulation of endocytosis, receptor-mediated endocytosis, response to extracellular stimuli, and bone mineralization. Furthermore, the validation results demonstrated that the suppression of miR-199a-3p promoted proliferation, osteogenesis, and angiogenesis, while inhibiting apoptosis of OBs and HUVECs activities and exposed to high-dose Dex. Discussion This study identified differential expression profiles of ncRNAs, miRNAs and mRNAs related to the Exos-mediated pathway in SONFH through integrated analysis, and further demonstrated the negative role of miR‐199a‐3p in SONFH, involving proliferation, osteogenesis, and angiogenesis, as well as the regulation of apoptosis of OBs and HUVECs exposed to high-dose Dex through the hBMSCs-Exos-mediated pathway. Therefore, targeting miR‐199a‐3p may enhance the therapeutic efficacy of Exos-based treatments for SONFH.

Proteomic profiling of gills during carp edema virus infection provides insights into immune responses and cellular stress associated with koi sleepy disease.

A missense mutation in acyl-CoA synthetase ACSL4 reveals essential residues for catalytic activity in ferroptosis.

Although the pathogen Fusarium proliferatum is responsible for soybean root rot, the mechanisms underlying its pathogenicity remain unclear. We detected limited soybean resistance to six F. proliferatum strains isolated from China. To elucidate the mechanisms underlying F. proliferatum pathogenicity, we conducted RNA sequencing analysis of the F. proliferatum isolate Fp6-1 during the mycelial and infection stages. Transcriptome sequencing analysis identified 10 significantly upregulated candidate effector molecules; these were selected for subsequent transcriptional pattern analysis. Bioinformatics analysis predicted 80 candidate effectors that were cysteine-rich, contained signal peptides, lacked transmembrane domains, and were secreted extracellularly. The conserved domains, pathogenicity, and functions of these candidate effectors were assessed. Pathogen host interaction database comparisons demonstrated that 44 of the candidate effectors were associated with virulence. Among these, 12 were upregulated during the infection stage and contained the pectate lyase, Hce2, FKBP-C, abhydrolase, DUF196, SGNH hydrolase, CE4 superfamily, ZnMc pappalysin-like, GH16 Streptomyces laminarinase-like, MhpC, and glyco-hydro-11 domains. The majority of the predicted candidate effectors were upregulated during F. proliferatum infection. Given that domestic soybean cultivars resistant to F. proliferatum are scarce in China, this study provides invaluable resources for subsequent functional analyses and guidance for future soybean breeding efforts.

There is a need for dual action anti-virulence and anti-biofilm agents that target the opportunistic pathogen Staphylococcus aureus . Previous research determined that 0.8 mg/mL 4-ethoxybenzoic acid (4EB) reduced S. aureus ATCC 6538 biofilm formation by 88% relative to untreated controls with moderate inhibition of planktonic cell growth. Here we report that 4EB impacted S. aureus virulence phenotypes across all growth phases, including alpha-hemolysin (Hla) and serine protease (SplB/C) exoprotein production (60% reduction), staphyloxanthin pigment accumulation (73% reduction) and alpha-hemolysis (>87% reduction) compared to untreated control cells. RT-qPCR analysis demonstrated that 4EB downregulated virulence gene expression, including >100-fold reduction of alpha-hemolysin ( hla ) and leukocidins ( lukDvEv ), and a 35-fold decrease of the response regulator SaeR. Phenol-soluble modulin (PSM) transcription by biofilm-grown cells was upregulated by 4EB more than 4-fold for α1-4 psm and β1-2 psm genes, while δ -toxin ( hld ) was unaffected. In silico molecular docking analysis revealed that 4EB has a strong binding affinity (ΔG < −6.0 kcal/mol) for 9 virulence-associated transcriptional regulators, including SaeS, IcaR and CodY. Analysis of gene transcription during late exponential phase growth determined that genes controlled by 7 of the 9 identified regulators were significantly impacted by 4EB. The docking analysis identified putative 4EB binding sites that share common features including valine and tyrosine amino acid residues. The combined in vitro and in silico analyses identified interactions with well-known virulence genes but also implicated an effect of 4EB on proteins less commonly associated with S. aureus pathogenesis. These findings suggested potential alternative targets for anti-virulence and anti-biofilm therapeutics.

Tendons and ligaments are crucial connective tissues linking bones and muscles, yet achieving full functional recovery after injury remains challenging. We investigated the characteristics of tendon stem/progenitor cells (TSPCs) by focusing on the declining tendon repair capacity with growth. Using single-cell RNA sequencing on Achilles tendon cells from 2- and 6-week-old mice, we identified Cd55 and Cd248 as novel surface antigen markers for TSPCs. Combining single-cell RNA sequencing with single-nucleus RNA and ATAC sequencing analyses revealed that Cd55- and Cd248-positive fractions in tendon tissue represent TSPCs, as confirmed by their expression of established TSPC markers, with this population decreasing at 6 weeks. We also identified candidate upstream transcription factors regulating these fractions. Functional analyses of isolated CD55/CD248-positive cells demonstrated high clonogenic potential and tendon differentiation capacity, forming functional tendon-like tissue in vitro. This study establishes CD55 and CD248 as novel TSPC surface antigens, potentially advancing tendon regenerative medicine and contributing to the development of new treatment strategies for tendon and ligament injuries.

ABSTRACTBackgroundCrisis and Liaison teams in Child and Adolescent Mental Health Services (CAMHS) offer intensive, short‐term support to young people experiencing mental health crisis in the community (Crisis) or admitted to acute hospitals (Liaison). There is no evidence‐based model for how these teams operate. The SAFER care bundle, designed to improve discharges from acute hospitals, has been adapted for use in mental health inpatient discharges for adults (SAFER‐MH) and young people (SAFER‐YMH). This study took a care bundle designed to improve discharges from CAMHS inpatient care (SAFER‐YMH) and used stakeholder feedback to adapt it for use in CAMHS Crisis and Liaison teams.DesignFocus groups were carried out with healthcare professionals (HCPs), young people and parents/carers to present the SAFER care bundle and discuss necessary adaptations for use in CAMHS Crisis and Liaison teams. Analysis of transcripts followed a Normalisation Process Theory (NPT) framework to identify barriers and facilitators to implementation and necessary adaptations.ResultsParticipants expressed that integrating the SAFER‐YCL care bundle into the electronic patient record, automatically pulling information from other forms, and providing a template for discharge letters and safety plans could serve as an aide‐memoire and potentially replace current discharge documents. It would need to avoid increasing documentation burden for staff and have flexibility to be administered by different staff members and at an appropriate time.ConclusionsThe SAFER‐YCL care bundle has been successfully developed for implementation in CAMHS Crisis and Liaison services, demonstrating potential to enhance transition experiences. Feasibility testing will be crucial to validate its effectiveness and facilitate successful integration into clinical practice.Patient or Public ContributionThis study was initially presented at the Nottinghamshire Healthcare NHS Foundation Trust's Involvement group of young people to gather their thoughts on it. They were supportive of the study design and gave constructive feedback on the study. A PPI representative with lived experience was part of the study team who was involved in developing and reviewing all study materials, was part of monthly reviews of the study's progress and supported data collection, analysis and write‐up of the study results.

The thioredoxin-interacting protein (TXNIP) pathway is a central regulator of oxidative stress and contributes to vascular pathology. Here, we define how stress-responsive mRNA methylation controls TXNIP expression and drives abdominal aortic aneurysm (AAA). In angiotensin II (AngII)-infused ApoE -/- mice, TXNIP was markedly elevated in vascular smooth muscle cells (VSMCs), as confirmed by histological, protein, and transcript analyses. VSMC-specific TXNIP deletion (ApoE -/- TXNIP SM-/- ) significantly reduced AAA incidence, aortic remodeling, and elastic fiber degradation, establishing its essential role in disease progression. Mechanistic studies revealed that elevated m6A methylation, catalyzed by METTL3, promoted TXNIP translation via YTHDF1 binding to m6A sites within the 3' untranslated region (UTR), whereas YTHDF2 downregulation in AAA stabilized TXNIP transcripts. TXNIP translation also proceeded through a cap-independent process enhanced by mTOR inhibition. These findings identify an integrated m6A-dependent regulatory program governing TXNIP expression and highlight therapeutic opportunities for targeting AAA progression.

Drought poses a critical threat to global agriculture, food security, and livestock sustainability. In Brassica napus L. (B. napus), a major oilseed crop, yield losses under water deficit underscore the urgent need for breeding strategies that improve water-use efficiency. Here, this study demonstrates that CIPK9 loss-of-function lines of B. napus displayed enhanced drought tolerance compared with the wild-type (WT). Yeast two-hybrid, split-luciferase complementation (LCI), and bimolecular fluorescence complementation (BiFC) assays showed that BnaCIPK9 physically interacts with PP2C39 both in vivo and in vitro. Transcript analysis and enzymatic assays further revealed that CIPK9 functioned in an abscisic acid (ABA)-dependent pathway regulating ABA biosynthesis and enhanced antioxidant capacity by promoting reactive oxygen species (ROS) scavenging. In Arabidopsis, both pp2c39 and cipk9 mutants exhibited stronger drought tolerance than WT plants. Notably, cipk9 mutants showed greater detoxification capacity, resulting in reduced ROS accumulation, higher stomatal conductance, and increased growth, whereas pp2c39 mutants triggered hyperactive stress signaling, leading to elevated ROS levels, lower stomatal conductance, and growth inhibition. These findings highlight a dual drought-response strategy that balances stress defense with cellular homeostasis to sustain growth. Specifically, PP2C39 mediates ABA-induced stress signaling, while the PP2C39-CIPK9 module mitigates its cytotoxic consequences, and their interaction links two distinct pathways to maintain equilibrium between defense and growth. This work provides mechanistic insights for breeding, suggesting that exploiting functional redundancy can reduce excessive self-regulation to improve stress resilience while avoiding modifications that overactivate stress responses and compromise plant development.

Spatane diterpenoids from the Hainan soft coral Sinularia nanolobata: emerging anticancer agents with c-MET inhibitory potential.

There is a lack of evidence to support UK and international clinical recommendations to delay cervical screening to 12-weeks postnatal. In previous studies, half of women were out of date for screening by the end of pregnancy and the majority would be more likely to take up cervical screening, if offered at the 6-week postnatal check-up. We explored views about postnatal cervical screening the acceptability of offering cervical screening, using conventional and urine self-sampling, earlier within the postnatal period. A cross-sectional qualitative design was used with recruitment from a larger questionnaire-based study. Twenty-six online semi-structured interviews were conducted with 26 pregnant or recently pregnant participants. Interviews were transcribed and pseudonymised. A topic guide was developed, and data analysed using inductive reflexive thematic analysis. Three themes were generated from qualitative analysis of verbatim interview transcripts: 1) A window of opportunity; 2) Am I ready yet? Postpartum recovery; and 3) Neglect of women's health in and around pregnancy. Overall, there was a perception that women's health was not a priority in the postnatal period compared with their babies. This is the first study to use qualitative interview methods to explore women's views about the offer of cervical screening alongside the postnatal check-up. Results support the feasibility of a clinical trial to test the accuracy and effect on uptake of offering cervical screening at the postnatal check-up, although recognised it might be too soon for some. This should be considered in future feasibility research that includes assessment of concurrent acceptability. This study was performed following focus groups in a quality improvement project, designed to increase uptake of cervical screening in women and people who were pregnant or recently pregnant. The suggestion for combining cervical screening with the routine 6-week postnatal follow up was an idea generated by new parents and GP practice staff. The Somerset Maternity Voices group provided feedback on study materials, including the consent form and posters. The semi-structured interview topic guide was designed following free-text comments in the pre-PINCS web-based survey, results of which are published separately. Female pregnant and recently pregnant people, regardless of current gender identity, were included in this study. In line with the Royal College of Obstetricians and Gynaecologists language guide, we will use 'women' to describe participants. Trial was registered with the National Institute for Health and Care Research Central Portfolio Management System (CPMS ID: 55489) and https://bepartofresearch.nihr.ac.uk/.

ABSTRACTObjectiveA major challenge in developing the psychology workforce is the time and cost of training and supervising provisional psychologists. CoreConnect was a pilot training programme provided for provisional psychologists, employed by one of four partnering organisations based in regional NSW. This study aimed to explore key stakeholders' perceptions of their outcomes and experiences with CoreConnect and collate recommendations for continuous improvement.SettingCommunity‐based mental health services in Central West NSW, including private practices, not‐for‐profit and NSW Health organisations.ParticipantsThe study utilised a sample of 17 provisional psychologists, seven clinical supervisors and six employers involved with CoreConnect.DesignA qualitative descriptive approach was utilised. Data were collected using open‐ended surveys and semi‐structured interviews over the initial 12 months of the training programme.ResultsThematic analyses of interview transcripts and survey questions provided five key themes. CoreConnect was perceived to support the provisional psychologists' professional growth and confidence, accelerate their learning and applicability of skills to their professional practice, and promote peer connection and networking. CoreConnect was perceived to increase the attraction, recruitment and retention of provisional psychologists within participating organisations and enabled time and cost savings for supervisors and employers. Recommendations for improving CoreConnect were identified.ConclusionsKey stakeholders indicated CoreConnect produced valued learning and professional outcomes for provisional psychologists, provided time and cost savings for supervisors and employers and assisted organisations to more efficiently develop and train their provisional psychologists. The CoreConnect model is likely to be useful for supporting mental health workforce development across Australia.

Paediatric and adolescent fertility preservation procedural training and service provision: A qualitative study exploring views of clinicians in Australia and New Zealand.

Light-responsive α-TOS liposomal nanocarriers Co-delivering TiO2 and doxorubicin for the treatment of breast cancer.

Integrated single-cell and transcriptional analysis of neutrophil migrasome-associated gene mechanisms in ARDS.

Dysregulation of hepatopancreatic microRNAs in Penaeus vannamei in response to Ecytonucleospora hepatopenaei (EHP) infection: Implications for innate immunity and metabolic function.

Role of microRNAs in the regulation of RKIP and signaling pathways in cancer.

Ancestral exposure to amitriptyline disrupts the behavior and gene expression in zebrafish F2 offspring.