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The human vaginal epithelium is a crucial component of numerous reproductive processes and serves as a vital protective barrier against pathogenic invasion. Despite its significance, a comprehensive exploration of its molecular profiles, including molecular expression and distribution across its multiple layers, has not been performed. In this study, we perform a spatial transcriptomic analysis within the vaginal wall of human fetuses to fill this knowledge gap. We successfully categorize the vaginal epithelium into four distinct zones based on transcriptomic profiles and anatomical features. This approach reveals unique transcriptomic signatures within these regions, allowing us to identify differentially expressed genes and uncover novel markers for distinct regions of the vaginal epithelium. Additionally, our findings highlight the varied expressions of keratin ( KRT) genes across different zones of the vaginal epithelium, with a gradual shift in expression patterns observed from the basal layer to the surface/superficial layer. This suggests a potential differentiation trajectory of the human vaginal epithelium, shedding light on the dynamic nature of this tissue. Furthermore, abundant biological processes are found to be enriched in the basal zone by KEGG pathway analysis, indicating an active state of the basal zone cells. Subsequently, the expressions of latent stem cell markers in the basal zone are identified. In summary, our research provides a crucial understanding of human vaginal epithelial cells and the complex mechanisms of the vaginal mucosa, with potential applications in vaginal reconstruction and drug delivery, making this atlas a valuable tool for future research in women’s health and reproductive medicine.

Oligosaccharides derived from agar, that is, agarooligosaccharides and neoagarooligosaccharides, have demonstrated various kinds of bioactivities which have been utilized in a variety of fields. Enzymatic hydrolysis is a feasible approach that principally allows for obtaining specific agar oligosaccharides in a sustainable way at an industrial scale. This review summarizes recent technologies employed to improve the properties of agarase. Additionally, the relationship between the degree of polymerization, bioactivities, and potential applications of agar-derived oligosaccharides for pharmaceutical, food, cosmetic, and agricultural industries are discussed. Engineered agarase exhibited general improvement of enzymatic performance, which is mostly achieved by truncation. Rational and semi-rational design assisted by computational methods present the latest strategy for agarase improvement with greatest potential to satisfy future industrial needs. Agarase immobilized on magnetic Fe3O4 nanoparticles via covalent bond formation showed characteristics well suited for industry. Additionally, albeit with the relationship between the degree of polymerization and versatile bioactivities like anti-oxidants, anti-inflammatory, anti-microbial agents, prebiotics and in skin care of agar-derived oligosaccharides are discussed here, further researches are still needed to unravel the complicated relationship between bioactivity and structure of the different oligosaccharides. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can maternal serum levels of soluble programmed cell death-1 (sPD-1) and its ligand (sPD-L1) serve as biomarkers for missed miscarriage (MM)? SUMMARY ANSWER Serum sPD-L1 levels are significantly decreased in MM patients and may serve as a potential predictive biomarker for miscarriage. WHAT IS KNOWN ALREADY Programmed cell death-1 (PD-1) and its ligand (PD-L1) comprise important immune inhibitory checkpoint signaling to maintain pregnancy. Their soluble forms are detectable in human circulation and are associated with immunosuppression. STUDY DESIGN, SIZE, DURATION Three independent cohorts attending tertiary referral hospitals were studied. The first (discovery) cohort was cross-sectional and included MM patients and healthy pregnant (HP) women matched on BMI. The second validation cohort contained MM patients and women with legally induced abortion (IA). The third prospective observational study recruited subjects requiring IVF treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS In the discovery cohort, we enrolled 108 MM patients and 115 HP women who had a full-term pregnancy at 6–14 weeks of gestation. In the validation cohort, we recruited 25 MM patients and 25 women with IA. Blood samples were collected at the first prenatal visit for HP women or on the day of dilatation and curettage surgery (D&C) for MM and IA subjects to determine serum sPD-1 and sPD-L1 levels. Placenta samples were harvested during the D&C within the validation cohort to measure gene and protein expression. The prospective cohort collected serial blood samples weekly from 75 volunteers with embryo transfer (ET) after IVF. MAIN RESULTS AND THE ROLE OF CHANCE Circulating sPD-L1 levels were reduced by 50% in patients with MM (55.7 ± 16.04 pg/ml) compared to HP controls (106.7 ± 58.46 pg/ml, P  <   0.001) and the difference remained significant after adjusting for maternal age and gestational age, whereas no significant differences in sPD-1 level were observed. Likewise, serum sPD-L1 was lower in MM patients than in IA subjects and accompanied by downregulated PD-L1-related gene expression levels in the placenta. In the IVF cohort, applying the changing rate of sPD-L1 level after ET achieved a predictive performance for miscarriage with receiver operating characteristics = 0.73 (95% CI: 0.57–0.88, P  <   0.01). LIMITATIONS, REASONS FOR CAUTION The study was mainly confined to East Asian pregnant women. Further large prospective pregnancy cohorts are required to validate the predictive performance of sPD-L1 on miscarriage. WIDER IMPLICATIONS OF THE FINDINGS Reduced circulating sPD-L1 level and downregulated placental PD-L1 expression in miscarriage indicate that dysfunction in PD-L1 signals is a potential underlying mechanism for pregnancy loss. Our findings further extend the importance of the PD-L1 axis in pregnancy maintenance in early pregnancy. STUDY FUNDING/COMPETING INTEREST(S) This study was financially supported by grants from the Subject Innovation Team of Shaanxi University of Chinese Medicine (2019-Y502), General Research Fund (14122021), and Key Laboratory of Model Animal Phenotyping and Basic Research in Metabolic Diseases (2018KSYS003). The authors declare that they have no competing interests to be disclosed. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Objective: This study provides a comprehensive overview of the knowledge structure and research hotspots regarding barriers and strategies for the implementation of clinical practice guidelines., Methods: Publications on barriers and strategies for guideline implementation were searched for on Web of Science Core Collection from database inception to October 24, 2022. R package bibliometrix, VOSviewer, and CiteSpace were used to conduct the analysis., Results: The search yielded 21,768 records from 3,975 journals by 99,998 authors from 3,964 institutions in 186 countries between 1983 and 2022. The number of published papers had a roughly increasing trend annually. The United States, the United Kingdom, and Canada contributed the majority of records. The University of Toronto, the University of Washington, and the University of Sydney were the biggest node in their cluster on the collaboration network map. The three journals that published the greatest number of relevant studies were Implementation Science , BMJ Open , and BMC Health Services Research . Grimshaw JM was the author with the most published articles, and was the second most co-cited author. Research hotspots in this field focused on public health and education, evidence-based medicine and quality promotion, diagnosis and treatment, and knowledge translation and barriers. Challenges and barriers, as well as societal impacts and inequalities, are likely to be key directions for future research., Conclusions: This is the first bibliometric study to comprehensively summarize the research trends of research on barriers and strategies for clinical practice guideline implementation. A better understanding of collaboration patterns and research hotspots may be useful for researchers., Spanish Abstract: http://links.lww.com/IJEBH/A247., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 JBI. Unauthorized reproduction of this article is prohibited.)

'Antibiotics under our feet' is a Scottish citizen science project that aimed to raise science capital in primary school learners and their teachers through measurement of microbial diversity in urban soil samples in the search for novel antimicrobial compounds. Resistance to antibiotics is rising, posing a global threat to human health. Furthermore, science, technology, engineering and mathematics (STEM) skills are in crisis, jeopardising our capacity to mobilise as a society to fight antimicrobial resistance (AMR). Originally conceived as a response to the AMR and STEM emergencies, our project was hit by the unprecedented challenge of engaging with schools during the COVID-19 pandemic. We describe how we adapted our project to enable remote participation from primary schools and youth groups, utilising COVID-19 response initiatives as opportunities for multi-level co-creation of resources with learners in primary, secondary, and higher education. We produced portable kit boxes for soil sample collection with learning activities and videos linked to the Scottish Curriculum for Excellence. We also addressed glaring project specific content gaps relating to microbiology on English and Simple English Wikipedia. Our hybrid model of working extended our geographical reach and broadened inclusion. We present here the inception, implementation, digital resource outputs, and discussion of pedagogical aspects of 'Antibiotics under our feet'. Our strategies and insights are applicable post-pandemic for educators to develop STEM skills using soil, microbes, and antibiotics as a theme., Competing Interests: The authors declare that no competing interests exist., (Copyright © 2024 The Authors.)