Ribosome biogenesis requires numerous trans-acting factors, some of which are deeply conserved. In Bacteria, the endoribonuclease YbeY is believed to be involved in 16S rRNA 3′-end processing and its loss was associated with ribosomal abnormalities. In Eukarya, YBEY appears to generally localize to mitochondria (or chloroplasts). Here we show that the deletion of human YBEY results in a severe respiratory deficiency and morphologically abnormal mitochondria as an apparent consequence of impaired mitochondrial translation. Reduced stability of 12S rRNA and the deficiency of several proteins of the small ribosomal subunit in YBEY knockout cells pointed towards a defect in mitochondrial ribosome biogenesis. The specific interaction of mitoribosomal protein uS11m with YBEY suggests that the latter helps to properly incorporate uS11m into the nascent small subunit in its late assembly stage. This scenario shows similarities with final stages of cytosolic ribosome biogenesis, and may represent a late checkpoint before the mitoribosome engages in translation.

During tissue regeneration, mesenchymal stem cells can support endothelial cells in the process of new vessel formation. For a functional interaction of endothelial cells with mesenchymal stem cells a vascular inductive microenvironment is required. Using a cellular model for neo-vessel formation, we could show that newly formed vascular structures emanated from the embedded aggregates, consisting of mesenchymal stem cells co-cultured with autologous human umbilical vein endothelial cells, into avascular human platelet lysate-based matrices, bridging distances up to 5 mm to join with adjacent aggregates with the same morphology forming an interconnected network. These newly formed vascular sprouts showed branch points and generated a lumen, as sign of mature vascular development. In two-dimensional culture, we detected binding of mesenchymal stem cells to laser-damaged endothelial cells under flow conditions, mimicking the dynamics in blood vessels. In conclusion, we observed that mesenchymal stem cells can support human umbilical vein endothelial cells in their vitality and functionality. In xeno-free human platelet lysate-based matrices, endothelial cells form complex vascular networks in a primarily avascular scaffold with the aid of mesenchymal stem cells, when co-cultured in three-dimensional spherical aggregates. Under dynamic conditions, representing the flow rate of venous vessel, mesenchymal stem cells preferably bind to damaged endothelial cells presumably assisting in the healing process.

The prevalence of centenarians, people who lived 100 years and longer, is steadily growing in the last decades. This exceptional longevity is based on multifaceted processes influenced by a combination of intrinsic and extrinsic factors such as sex, (epi-)genetic factors, gut microbiota, cellular metabolism, exposure to oxidative stress, immune status, cardiovascular risk factors, environmental factors, and lifestyle behavior. Epidemiologically, the incidence rate of cardiovascular diseases is reduced in healthy centenarians along with late onset of age-related diseases compared with the general aged population. Understanding the mechanisms that affect vascular ageing in centenarians and the underlying factors could offer valuable insights for developing strategies to improve overall healthy life span in the elderly. This review discusses these key factors influencing vascular ageing and how their modulation could foster healthy longevity.

With global demand for SARS-CoV-2 testing ever rising, shortages in commercially available viral transport media pose a serious problem for laboratories and health care providers. For reliable diagnosis of SARS-CoV-2 and other respiratory viruses, executed by Real-time PCR, the quality of respiratory specimens, predominantly determined by transport and storage conditions, is crucial. Therefore, our aim was to explore the reliability of minimal transport media, comprising saline or the CDC recommended Viral Transport Media (HBSS VTM), for the diagnosis of SARS-CoV-2 and other respiratory viruses (influenza A, respiratory syncytial virus, adenovirus, rhinovirus and human metapneumovirus) compared to commercial products, such as the Universal Transport Media (UTM). We question the assumptions, that the choice of medium and temperature for storage and transport affect the accuracy of viral detection by RT-PCR. Both alternatives to the commercial transport medium (UTM), HBSS VTM or saline, allow adequate detection of SARS-CoV-2 and other respiratory viruses, regardless of storage temperatures up to 28 °C and storage times up to 28 days. Our study revealed the high resilience of SARS-CoV-2 and other respiratory viruses, enabling proper detection in clinical specimens even after long-time storage at high temperatures, independent of the transport medium’s composition.

This preregistered ex vivo investigation examined the dentinal hybrid layer formation of a resinous infiltrant (Icon), with reference to both thickness (HLT) and homogeneity when combined with modified tunnel preparation (occlusal cavity only) and internal/external caries infiltration. The adhesives Syntac and Scotchbond MP were used as controls (Groups 1 and 3) or in combination with Icon (Groups 2 and 4). A split-tooth design using healthy third molars from 20 donors resulted in 20 prepared dentine cavities per experimental group. The cavity surfaces (n = 80) were etched (37% H₃PO₄), rinsed, and air-dried. Rewetting with ethanol was followed by application of the respective primers. After labeling with fluorescent dyes, either Syntac Adhesive/Heliobond or Scotchbond MP Adhesive was used alone or supplemented with Icon. HLT, as evaluated by scanning electron microscopy, did not significantly differ (P > 0.05), and confocal laser scanning microscopy revealed homogeneously mixed/polymerized resin-dentine interdiffusion zones in all groups. Icon can be successfully integrated into an ethanol-wet dentine bonding strategy, and will result in compact and homogeneous hybrid layers of comparable thickness considered equivalent to the non-Icon controls, thus allowing for preservation of the tooth’s marginal ridge and interdental space in the case of internal/external infiltration of proximal caries.

Acute myeloid leukemia (AML) is a heterogenous disease characterized by the clonal expansion of myeloid progenitor cells. Despite recent advancements in the treatment of AML, relapse still remains a significant challenge, necessitating the development of innovative therapies to eliminate minimal residual disease. One promising approach to address these unmet clinical needs is natural killer (NK) cell immunotherapy. To implement such treatments effectively, it is vital to comprehend how AML cells escape the NK-cell surveillance. Signal transducer and activator of transcription 3 (STAT3), a component of the Janus kinase (JAK)-STAT signaling pathway, is well-known for its role in driving immune evasion in various cancer types. Nevertheless, the specific function of STAT3 in AML cell escape from NK cells has not been deeply investigated. In this study, we unravel a novel role of STAT3 in sensitizing AML cells to NK-cell surveillance. We demonstrate that STAT3-deficient AML cell lines are inefficiently eliminated by NK cells. Mechanistically, AML cells lacking STAT3 fail to form an immune synapse as efficiently as their wild-type counterparts due to significantly reduced surface expression of intercellular adhesion molecule 1 (ICAM-1). The impaired killing of STAT3-deficient cells can be rescued by ICAM-1 overexpression proving its central role in the observed phenotype. Importantly, analysis of our AML patient cohort revealed a positive correlation between ICAM1 and STAT3 expression suggesting a predominant role of STAT3 in ICAM-1 regulation in this disease. In line, high ICAM1 expression correlates with better survival of AML patients underscoring the translational relevance of our findings. Taken together, our data unveil a novel role of STAT3 in preventing AML cells from escaping NK-cell surveillance and highlight the STAT3/ICAM-1 axis as a potential biomarker for NK-cell therapies in AML.