Propagation of neuronal micronuclei regulates microglial characteristics.

Microglia-resident immune cells in the central nervous system-undergo morphological and functional changes in response to signals from the local environment and mature into various homeostatic states. However, niche signals underlying microglial differentiation and maturation remain unknown. Here, we show that neuronal micronuclei (MN) transfer to microglia, which is followed by changing microglial characteristics during the postnatal period.

mtSTAT3 suppresses rheumatoid arthritis by regulating Th17 and synovial fibroblast inflammatory cell death with IL-17-mediated autophagy dysfunction.

Th17 cells are activated by STAT3 factors in the nucleus, and these factors are correlated with the pathologic progression of rheumatoid arthritis (RA). Recent studies have demonstrated the presence of STAT3 in mitochondria, but its function is unclear. We investigated the novel role of mitochondrial STAT3 (mitoSTAT3) in Th17 cells and fibroblast-like synoviocytes (FLSs) and analyzed the correlation of mitoSTAT3 with RA.

Integrins identified as potential prognostic markers in osteosarcoma through multi-omics and multi-dataset analysis.

Osteosarcoma represents 20% of primary malignant bone tumors globally. Assessing its prognosis is challenging due to the complex roles of integrins in tumor development and metastasis. This study utilized 209,268 osteosarcoma cells from the GEO database to identify integrin-associated genes using advanced analysis methods.

Pre-exposure of abundant species to disturbance improves resilience in microbial metacommunities.

Understanding factors influencing community resilience to disturbance is critical for mitigating harm at various scales, including harm from medication to gut microbiota and harm from human activity to global biodiversity, yet there is a lack of data from large-scale controlled experiments. Factors expected to boost resilience include prior exposure to the same disturbance and dispersal from undisturbed patches. Here we set up an in vitro system to test the effect of disturbance pre-exposure and dispersal represented by community mixing.

Evolution of the umbilical cord blood proteome across gestational development.

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth.

Exploration of the shared diagnostic genes and molecular mechanism between obesity and atherosclerosis via bioinformatic analysis.

Obesity (OB) and atherosclerosis (AS) represent two highly prevalent and detrimental chronic diseases that are intricately linked. However, the shared genetic signatures and molecular pathways underlying these two conditions remain elusive. This study aimed to identify the shared diagnostic genes and the associated molecular mechanism between OB and AS.

Changes in the potato rhizosphere microbiota richness and diversity occur in a growth stage-dependent manner.

Plant root and soil-associated microbiomes are influenced by niches, including bulk and rhizosphere soil. In this work, we collected bulk and rhizosphere soil samples at four potato developmental stages (leaf growth, flowering, tuber elongation and harvest) to identify whether rhizosphere microbiota are structured in a growth stage-dependent manner. The bacterial and fungal microbiota showed significant temporal differences in the rhizosphere and bulk soil.

Acid sphingomyelinase activity suggests a new antipsychotic pharmaco-treatment strategy for schizophrenia.

Schizophrenia is a chronic and severe mental disorder. It is currently treated with antipsychotic drugs (APD). However, APD's work only in a limited number of patients and may have cognition impairing side effects.

Challenges and opportunities for digital twins in precision medicine from a complex systems perspective.

Digital twins (DTs) in precision medicine are increasingly viable, propelled by extensive data collection and advancements in artificial intelligence (AI), alongside traditional biomedical methodologies. We argue that including mechanistic simulations that produce behavior based on explicitly defined biological hypotheses and multiscale mechanisms is beneficial. It enables the exploration of diverse therapeutic strategies and supports dynamic clinical decision-making through insights from network science, quantitative biology, and digital medicine.

Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity.

Cancer cells frequently rewire their metabolism to support proliferation and evade immune surveillance, but little is known about metabolic targets that could increase immune surveillance. Here we show a specific means of mitochondrial respiratory complex I (CI) inhibition that improves tumor immunogenicity and sensitivity to immune checkpoint blockade (ICB). Targeted genetic deletion of either Ndufs4 or Ndufs6, but not other CI subunits, induces an immune-dependent growth attenuation in melanoma and breast cancer models.

Protocatechuic aldehyde sensitizes BRAF-mutant melanoma cells to temozolomide through inducing FANCD2 degradation.

Temozolomide (TMZ)-based chemotherapy is a primary regimen for melanoma patients who have failed targeted therapy or immunotherapy. However, the low response rate of TMZ-based chemotherapy challenges the patients' prognosis. BRAF mutation is the most frequently mutated site in melanoma.

Microfluidic mixing probe: generating multiple concentration-varying flow dipoles.

This study advances microfluidic probe (MFP) technology through the development of a 3D-printed Microfluidic Mixing Probe (MMP), which integrates a built-in pre-mixer network of channels and features a lined array of paired injection and aspiration apertures. By combining the concepts of hydrodynamic flow confinements (HFCs) and "Christmas-tree" concentration gradient generation, the MMP can produce multiple concentration-varying flow dipoles, ranging from 0 to 100%, within an open microfluidic environment. This innovation overcomes previous limitations of MFPs, which only produced homogeneous bioreagents, by utilizing the pre-mixer to create distinct concentration of injected biochemicals.

ERK-USP9X-coupled regulation of thymidine kinase 1 promotes both its enzyme activity-dependent and its enzyme activity-independent functions for tumor growth.

Thymidine kinase 1 (TK1), a crucial enzyme in DNA synthesis, is highly expressed in various cancers. However, the mechanisms underlying its elevated expression and the implications for tumor metabolism remain unclear. Here we demonstrate that activation of growth factor receptors enhances TK1 expression.

Molecular architecture of human LYCHOS involved in lysosomal cholesterol signaling.

Lysosomal membrane protein LYCHOS (lysosomal cholesterol signaling) translates cholesterol abundance to mammalian target of rapamycin activation. Here we report the 2.11-Å structure of human LYCHOS, revealing a unique fusion architecture comprising a G-protein-coupled receptor (GPCR)-like domain and a transporter domain that mediates homodimer assembly.

A multi-tissue longitudinal proteomics study to evaluate the suitability of post-mortem samples for pathophysiological research.

Recent developments in mass spectrometry-based proteomics have established it as a robust tool for system-wide analyses essential for pathophysiological research. While post-mortem samples are a critical source for these studies, our understanding of how body decomposition influences the proteome remains limited. Here, we have revisited published data and conducted a clinically relevant time-course experiment in mice, revealing organ-specific proteome regulation after death, with only a fraction of these changes linked to protein autolysis.

Organic solar cells with 20.82% efficiency and high tolerance of active layer thickness through crystallization sequence manipulation.

Printing of large-area solar panels necessitates advanced organic solar cells with thick active layers. However, increasing the active layer thickness typically leads to a marked drop in the power conversion efficiency. Here we developed an organic semiconductor regulator, called AT-β2O, to tune the crystallization sequence of the components in active layers.

Evidence of DNA methylation heterogeneity and epipolymorphism in kidney cancer tissue samples.

Clear cell renal cell carcinoma (ccRCC) is characterised by significant genetic heterogeneity, which has diagnostic and prognostic implications. Very limited evidence is available regarding DNA methylation heterogeneity. We therefore generate sequence level DNA methylation data on 136 multi-region tumour and normal kidney tissue from 18 ccRCC patients, along with matched whole exome sequencing (85 samples) and gene expression (47 samples) data on a subset of samples.

Prenatal inflammation impairs early CD11c-positive microglia induction and delays myelination in neurodevelopmental disorders.

Histological chorioamnionitis (HCA) is a form of maternal immune activation (MIA) linked to an increased risk of neurodevelopmental disorders in offspring. Our previous study identified neurodevelopmental impairments in an MIA mouse model mimicking HCA. Thus, this study investigated the role of CD11c microglia, key contributors to myelination through IGF-1 production, in this pathology.

Microbial secondary metabolites: advancements to accelerate discovery towards application.

Microbial secondary metabolites not only have key roles in microbial processes and relationships but are also valued in various sectors of today's economy, especially in human health and agriculture. The advent of genome sequencing has revealed a previously untapped reservoir of biosynthetic capacity for secondary metabolites indicating that there are new biochemistries, roles and applications of these molecules to be discovered. New predictive tools for biosynthetic gene clusters (BGCs) and their associated pathways have provided insights into this new diversity.

Norovirus replication, host interactions and vaccine advances.

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide in all age groups and cause significant disease and economic burden globally. To date, no approved vaccines or antiviral therapies are available to treat or prevent HuNoV illness. Several candidate vaccines are in clinical trials, although potential barriers to successful development must be overcome.

The association between metabolomic profiles of lifestyle and the latent phase of incident chronic kidney disease in the UK Population.

Chronic kidney disease (CKD) is a global health challenge associated with lifestyle factors such as diet, alcohol, BMI, smoking, sleep, and physical activity. Metabolomics, especially nuclear magnetic resonance(NMR), offers insights into metabolic profiles' role in diseases, but more research is needed on its connection to CKD and lifestyle factors. Therefore, we utilized the latest metabolomics data from the UK Biobank to explore the relationship between plasma metabolites and lifestyle factors, as well as to investigate the associations between various factors, including lifestyle-related metabolites, and the latent phase of CKD onset.

Use of approved cefazolin based intramammary dry goat treatment and its effects on the milk microbiota.

Intramammary dry-off treatment is widely considered an effective method for preventing and curing intramammary infection (IMI) in lactating cows; however, it is not commonly used in small ruminants like goats. Therefore, this study was designed to evaluate the effect of an approved cefazolin-based intramammary treatment on the milk microbiota of Alpine dairy goats during the dry and early lactation periods. Sixty goats were randomly selected based on bacteriological results and randomly allocated into the control group (CG) or the treatment group (TG).

Integrative genetics and multiomics analysis reveal mechanisms and therapeutic targets in vitiligo highlighting JAK STAT pathway regulation of CTSS.

Vitiligo is a complex autoimmune disease characterized by the loss of melanocytes, leading to skin depigmentation. Despite advances in understanding its genetic and molecular basis, the precise mechanisms driving vitiligo remain elusive. Integrating multiple layers of omics data can provide a comprehensive view of disease pathogenesis and identify potential therapeutic targets.