Hypertension seems to inevitably cause cardiac remodeling, increasing the mortality of patients. This study aimed to explore the molecular mechanism of CCAAT/enhancer-binding protein delta (CEBPD)-mediated oxidative stress and inflammation in hypertensive cardiac remodeling. The hypertensive murine model was established through angiotensin-II injection, and hypertensive mice underwent overexpressed CEBPD vector injection, cardiac function evaluation, and observation of histological changes. The cell model was established by angiotensin-II treatment and transfected with overexpressed CEBPD vector. Cell viability and surface area and oxidative stress (reactive oxygen species/superoxide dismutase/lactate dehydrogenase/malondialdehyde) were assessed, and inflammatory factors (TNF-α/IL-1β/IL-6/IL-10) were determined both in vivo and in vitro . The levels of CEBPD, miR-96-5p, inositol 1,4,5-trisphosphate receptor 1 (IP3R), natriuretic peptide B, and natriuretic peptide A, collagen I, and collagen III in tissues and cells were determined. The binding relationships of CEBPD/miR-96-5p/IP3R 3' untranslated region were validated. CEBPD was reduced in cardiac tissue of hypertensive mice, and CEBPD upregulation improved cardiac function and attenuated fibrosis and hypertrophy, along with reductions of reactive oxygen species/lactate dehydrogenase/malondialdehyde/TNF-α/IL-1β/IL-6 and increases in superoxide dismutase/IL-10. CEBPD enriched on the miR-96-5p promoter to promote miR-96-5p expression, whereas CEBPD and miR-96-5p negatively regulated IP3R. miR-96-5p silencing/IP3R overexpression reversed the alleviative role of CEBPD overexpression in hypertensive mice. In summary, CEBPD promoted miR-96-5p to negatively regulate IP3R expression to inhibit oxidative stress and inflammation, thereby alleviating hypertensive cardiac remodeling.

As a typical signal of hypoxia, the up-regulation of nitroreductase (NTR) expression has been widely used to evaluate the anoxic microenvironment of solid tumors. Herein, we propose a near infrared (NIR) fluorescent probe Q-NTR wakened up by NTR in mitochondria. The presence of strong electron-absorbing group nitro can quench fluorescence effectively and provide a sufficiently low background signal. Probe Q-NTR can detect the activity of NTR to evaluate the degree of hypoxia in tumor tissues. Due to its NIR emission, subcellular structure level imaging, and rapid response characteristics, it provides a practical tool for studying NTR activity and hypoxia related biological processes. This sensing scheme has been successfully applied to monitor endogenous NTR activity in subcellular structures (in mitochondria) in anoxic microenvironments and selectively stain cells in anoxic conditions, demonstrated its great potential in early cancer diagnosis. In addition, probe Q-NTR could accurately locate the hypoxic environment, achieving precise navigation during solid tumor resection. In summary, probe Q-NTR will lay the foundation for further research on cell metabolism, tumor metabolism, and solid tumor resection under hypoxic conditions in the future.

Abstract Water-soluble organic compounds (WSOC) are ubiquitous substances usually found in atmospheric particles. In this work, we report the use of nuclear resonance magnetic spectroscopy techniques (1H-NMR, 13C-NMR, and 2D-NMR) in the characterisation of the WSOC in an aerosol sampled from the remote coastal location of Bou-Ismail, Algeria. These techniques, preferentially chosen to be mainly applied in this contribution, allowed us the determination of the functional composition of WSOC aerosol and the evaluation of source signature of organic aerosol. It has been recorded that 4.8–7.8 ppm, the groups were mainly constituted of precursors of the aromatic amino acids tyrosine, phenylalanine, and tryptophan, which are usually used as herbicides and antibacterial agents in agriculture. Using the HSQC technique, by combining the two regions (6.5–8.5) ppm and (115–150) ppm, revealed the appearance of many peaks in biogenic samples, including biomass burning. Specific NMR spectral allows identification of source of several organic compounds and functional composition, so the surrounding organic aerosol sources can be adjusted. Along this study, the concentrations of PM10 varied between 15.66 and 142.19 µgm− 3.

BackgroundCompared to their healthy counterparts, patients with type 2 diabetes (T2D) can exhibit an altered gut microbiota composition, correlated with detrimental outcomes, including reduced insulin sensitivity, dyslipidemia, and increased markers of inflammation. However, a typical T2D microbiota profile is not established. The aim of this pilot study was to explore the gut microbiota and bacteria associated with prediabetes (pre-T2D) patients, and treatment naïve T2D patients, compared to healthy subjects.MethodsFecal samples were collected from patients and healthy subjects (from Norway). The bacterial genomic DNA was extracted, and the microbiota analyzed utilizing the bacterial 16S rRNA gene. To secure a broad coverage of potential T2D associated bacteria, two technologies were used: The GA-map® 131-plex, utilizing 131 DNA probes complementary to pre-selected bacterial targets (covering the 16S regions V3-V9), and the LUMI-Seq™ platform, a full-length 16S sequencing technology (V1-V9). Variations in the gut microbiota between groups were explored using multivariate methods, differential bacterial abundance was estimated, and microbiota signatures discriminating the groups were assessed using classification models.ResultsIn total, 24 pre-T2D patients, 18 T2D patients, and 52 healthy subjects were recruited. From the LUMI-Seq™ analysis, 10 and 9 bacterial taxa were differentially abundant between pre-T2D and healthy, and T2D and healthy, respectively. From the GA-map® 131-plex analysis, 10 bacterial markers were differentially abundant when comparing pre-T2D and healthy. Several of the bacteria were short-chain fatty acid (SCFA) producers or typical opportunistic bacteria. Bacteria with similar function or associated properties also contributed to the separation of pre-T2D and T2D from healthy as found by classification models. However, limited overlap was found for specific bacterial genera and species.ConclusionsThis pilot study revealed that differences in the abundance of SCFA producing bacteria, and an increase in typical opportunistic bacteria, may contribute to the variations in the microbiota separating the pre-T2D and T2D patients from healthy subjects. However, further efforts in investigating the relationship between gut microbiota, diabetes, and associated factors such as BMI, are needed for developing specific diabetes microbiota signatures.

Preeclampsia (PE) is a major complication of pregnancy with an incidence rate of 2‑8% and is a leading cause of maternal mortality and morbidity. The various consequences of severe preeclampsia for the fetus, neonate and child include intrauterine growth retardation (IUGR), fetal hypoxia, oligohydramnios, intrauterine fetal demise, increased perinatal mortality and morbidity, neurodevelopmental disorders and even irreversible brain damage (cerebral palsy). A number of studies have demonstrated that differences in maternal serum concentrations of angiogenic factors between preeclampsia and normotensive pregnancies can be used as biomarkers, either alone or in combination with other markers, to predict the development of PE. The presence in the maternal circulation of two proteins of placental origin, placental growth factor (PlGF) and soluble fms‑like tyrosine kinase 1 (sFlt‑1), has been shown to be of clinical value, as the sFlt‑1/PlGF ratio appears to be the optimal predictive tool for the development of PE. The measurement of their concentration in maternal serum in screening models, serves as predictive marker for the development of PE or IUGR later in gestation. However, further research is required to improve its clinical applicability and provide guidelines for its use worldwide to achieve more consistent clinical management of women with PE.

This study describes firefighters' on-scene decontamination procedure use post-working fire and frequency of adherence to best practice. This retrospective analysis of working fires was conducted using records from the ESO Data Collaborative (Austin, TX) national research database from January 1, 2021, to December 31, 2021. Documentation of decontamination procedures was examined among records with smoke or combustion products exposure. Firefighter and incident characteristics were evaluated. Descriptive statistics and univariable odds ratios were calculated. Among the 31,281 firefighters included in the study, 8.0% documented a fire-related exposure. Of those, 82% performed at least one on-scene decontamination procedure; 5% documented all decontamination procedures defined as best practices. The odds of documenting any decontamination procedure were significantly decreased among firefighters responding to incidents in rural areas compared with urban areas (odds ratio, 0.70). Fire personnel may not be taking all necessary decontamination steps post-working fires.

Abstract Study question What is the level of fertility awareness and attitudes to having children among Greek teenagers and adults? Summary answer Fertility awareness among Greek teenagers and adults is limited with fundamental misconceptions which may be defining attitudes and may impact family planning and reproductive autonomy. What is known already According to the Organization for Economic Co-operation and Development, Greece is among the countries with the highest maternal age at first birth worldwide, while the total fertility rate has decreased alarmingly. The shift towards delayed parenthood is attributed to the lack of education concerning fertility issues and family planning options within the reproductive age population. This leads to dramatic misinterpretations regarding reproductive dynamic and respective choices. This study aimed to present current data and identify knowledge gaps. This will indicate where future initiatives should be focused to improve fertility awareness and education while respecting reproductive autonomy and individualism. Study design, size, duration This was a mixed methods study using an anonymous, online questionnaire. A 41-item questionnaire for adults and a 46–item questionnaire for teenagers were developed originating from a validated questionnaire from a previously published survey conducted in the UK. A total of 780 respondents completed the survey, which was live between the 11th and 26th of May 2022. Participants/materials, setting, methods Participants were adults and teenagers aged 17-45, who had not yet had children but wanted to in the future. Online Survey Software & Tools for WEB design was employed to generate a friendly-format questionnaire for the respondents. The methodology employed was via CAWI (Computer Assisted Web Interviews). The questionnaire addressed demographics, knowledge on fertility matters, opinions and attitudes towards childbearing. Respondents were also offered the “prefer not to say”, and “don’t know” options. Main results and the role of chance The ideal age to have the first child differed significantly between men and women (32.33±4.50 vs 30.64±3.94; p < 0.001), as did the ideal age to have competed a family (38.71±5.18 vs 36.97±4.71; p < 0.001). Teenagers preferred to have completed their family at a younger age than the adults (33.82±5.87 vs 37.64±4.96; p < 0.001). The desired children number was 2.30±0.7 for men, 2.37±0.71 for women and 2.38±0.7 for teenagers. One third overestimated dramatically the start of fertility decline identifying it as age 46. Over 50% of men and teenagers were not aware of the timing of a women’s fertile window. Women seemed to be more informed on fertility and choose the physician as the educational resource (69%, 261/392), while men were mainly informed from their partners, and choose internet as the educational resource (67%,163/244). Women appeared more concerned with their fertility (191/392 vs 64/244) and felt more pressure to have children compared to men (135/392 vs 54/244; p = 0.02) mainly by their family. Interestingly, relating to reasons that my affected the decision to have children, the most common response for women was “I am not financially ready” (45%, 175/392), compared to men’s “I am ready to have children now” (39%, 96/244). Limitations, reasons for caution The fact that more women than men were included in the teenagers’ group posed a limitation. This study portrays knowledge and attitudes of a population of reproductive age that wants to have children, and hence cannot reflect on knowledge and attitudes on fertility of the general population. Wider implications of the findings Findings identify misinterpretations that may jeopardize family-planning, and lead to unintentional childlessness and age-related infertility. The desired number of children was greater than the actual number reported by OECD. This data calls the scientific community to enable informed reproductive choices by working interdisciplinary towards all-inclusively educating the general population. Trial registration number Not applicable

Abstract Study question Could microRNA dysregulation be an underlying molecular mechanism leading to the observed increased prevalence of cancer in patients with Sertoli-cell only syndrome (SCOS)? Summary answer Patients with SCOS are characterized by altered microRNA profiles and dysregulated gene pathways involved in SCOS pathophysiology and in cell-cycle control and therefore in carcinogenesis. What is known already Sertoli cell-only syndrome constitutes a histopathological subtype of non-obstructive azoospermia, affecting 26.3–57.8% of azoospermia patients. It is characterized by partial or complete absence of active spermatogenesis due to germ cell aplasia. Except from infertility, SCOS is associated with increased risk of testicular nodules and cancer, rendering research on the topic essential. Despite advances, the underlying molecular mechanisms connecting SCOS with cancer remain unknown. Data demonstrates that microRNAs could play crucial roles in both SCOS pathophysiology and carcinogenesis. Identifying relevant microRNAs and conducting in-silico analysis on affected pathways may lead to mapping the way forward. Study design, size, duration A systematic review was performed in PubMed/Medline and Embase up to April 2022. Only full-length original studies in humans were included. Strict inclusion-exclusion criteria were applied aiming to select studies comparing microRNA profiling between SCOS cases versus men with normal spermatogenesis or men with proven fertility. Following study selection, data on altered microRNA expression patterns were analyzed to underline differences between the abovementioned groups. Subsequently, in-silico functional analysis was performed to compare affected gene pathways. Participants/materials, setting, methods The studied population consisted of SCOS cases. Men with normal spermatogenesis or proven fertility served as the control group. Predicted microRNA–target pairs were retrieved from microT-CDS, while a 0.8 cutoff threshold was applied. The GTEx repository was used to identify microRNA-targeted genes in the testis. Annotations derived from Ensembl and miRbase. Gene-set enrichment analysis was performed employing the KEGG-database. Fisher’s exact test was performed in R package limma, setting a 0.01 p-value threshold. Main results and the role of chance Four studies reported altered microRNA expression profiles in SCOS (n = 45) versus normal spermatogenesis cases or men of proven fertility (n = 16). Functional analysis revealed that six microRNAs, which were downregulated in the SCOS cases, namely hsa-miR-34b-5p, hsa-miR-202-3p, hsa-miR-34c-5p, hsa-miR-449a, hsa-miR-141-3p, and hsa-miR-34b-3p, affected 66 statistically significant gene-targets in the testis. Two pathways were reported to be statistically significantly dysregulated from these microRNAs, namely the ‘’microRNAs in cancer’’ pathway (40 affected genes, p-value = 0.004), and the ‘’TGF-beta signaling’’ pathway (26 affected genes, p-value = 0.01). Furthermore, four microRNAs, namely hsa-miR-10b-5p, hsa-miR-4270, hsa-miR-181c-5p, and hsa-miR-605-3p, reported to be upregulated in the SCOS group. These microRNAs had 108 statistically significant gene-targets in the testis. Three pathways were statistically significantly dysregulated from these microRNAs, namely the ‘’Herpes simplex virus 1 infection’’ pathway (61 affected genes, p-value = 0.01), the ‘’microRNAs in cancer’’ pathway (28 affected genes, p-value = 0.01), and the ‘’longevity regulating’’ pathway (19 affected genes, p-value = 0.01). The molecular role of the affected gene pathways in proper cell-cycle regulation and germ cell differentiation is herein underlined as critical. In the disrupted testicular microenvironment of the SCOS cases these disrupted genes may act as inducers of carcinogenic mechanisms. Limitations, reasons for caution The main limitation is the small number of the included studies and the small number of participants investigated per study, especially with regards to the control group. Moreover, the observed heterogeneity among the studies regarding the molecular tools employed for the microRNA profiling is another reason for caution. Wider implications of the findings Our data suggest that the dysregulation of microRNAs affecting several gene pathways that control cell-cycle and differentiation may lead to increased cancer risk in SCOS cases. Further studies employing our findings as a starting point will indicate whether microRNA profiling can serve as an effective evaluation tool for cancer predisposition. Trial registration number Not applicable

Apicomplexan parasites, including Toxoplasma gondii, encode many plant-like proteins, which play significant roles and present attractive targets for drug development. In this study, we have characterized the plant-like protein phosphatase PPKL, which is unique to the parasite and absent in its mammalian host. We have shown that its localization changes as the parasite divides. In non-dividing parasites, it is present in the cytoplasm, nucleus, and preconoidal region. As the parasite begins division, PPKL is enriched in the preconoidal region and the cortical cytoskeleton of the nascent parasites. Later in the division, PPKL is present in the basal complex ring. Conditional knockdown of PPKL showed that it is essential for parasite propagation. Moreover, parasites lacking PPKL exhibit uncoupling of division, with normal DNA duplication but severe defects in forming daughter parasites. While PPKL depletion does not impair the duplication of centrosomes, it affects the rigidity and arrangement of the cortical microtubules. Both Co-Immunoprecipitation and proximity labeling identified the kinase DYRK1 as a potential functional partner of PPKL. Complete knockout of DYRK1 phenocopies lack of PPKL, strongly suggesting a functional relationship between these two signaling proteins. Global phosphoproteomics analysis revealed a significant increase in phosphorylation of the microtubule-associated proteins SPM1 in PPKL-depleted parasites, suggesting PPKL regulates the cortical microtubules by mediating the phosphorylation state of SPM1. More importantly, the phosphorylation of cell cycle-associated kinase Crk1, a known regulator of daughter cell assembly, is altered in PPKL-depleted parasites. Thus, we propose that PPKL regulates daughter parasite development by influencing the Crk1-dependent signaling pathway.