Explore the vast range of titles available.

The rhesus macaque is one of the closest evolutionary relatives to humans, making the study of alternative splicing (AS) during its early embryonic development highly valuable for understanding human embryogenesis and related diseases. However, systematic studies in this context remain limited. Here, a comprehensive bioinformatic analysis of AS was performed using RNA-seq data spanning early rhesus macaque embryogenesis. We identified multiple previously unannotated zygotic genome activation (ZGA) genes, thereby refining the rhesus macaque ZGA gene repertoire. The landscape of AS and differential AS events (DASEs) across early stages was characterized, revealing dynamic and stage-specific regulation, with a marked increase in AS events from the 8-cell to morula stages. In addition, weighted gene co-expression network analysis identified 35 key splicing factors (SFs) involved in regulating early rhesus macaque embryonic development. Finally, we calculated the correlation between differentially expressed SFs and DASEs during the ZGA process, and identified potential regulatory relationships between several SFs (TRA2B, IGF2BP1, HNRNPAB, and MATR3) and specific DASEs. Collectively, this study provides the first systematic analysis of AS dynamics and regulation in early rhesus macaque embryogenesis, highlighting its critical role in development and offering a valuable reference for understanding AS in early human embryos.

Alternative splicing (AS) plays an essential role in development, differentiation and carcinogenesis. However, the mechanisms underlying splicing regulation during mouse embryo gastrulation remain unclear. Based on spatial-temporal transcriptome and epigenome data, we detected the dynamics of AS and revealed its regulatory mechanisms across primary germ layers during mouse gastrulation, spanning developmental stages from E6.5 to E7.5. Subsequently, the dynamic expression of splicing factors (SFs) during gastrulation was characterized, while the expression patterns and functions of germ layer-specific SFs were identified. The results indicate that AS and differential alternative splicing events (DASEs) exhibit dynamic changes and are significantly abundant during the late stage of gastrulation. Similarly, SFs demonstrate stage-specific expression, with elevated levels observed during the middle and late stages of gastrulation. Epigenetic signals associated with SFs and AS sites demonstrate significant enrichment and undergo dynamic changes throughout gastrulation. Overall, this study offers a systematic analysis of AS during mouse gastrulation, identifies primary germ layer-specific AS events, and characterizes the expression patterns of SFs and the associated epigenetic signals. These findings enhance the understanding of the mechanisms underlying the formation of the three germ layers during mammalian gastrulation, with a focus on pre-mRNA AS.

Solid papillary carcinoma of the breast is a rare histopathological subtype of papillary neoplasms, and its in situ variant localized to the nipple is particularly uncommon. Current oncology literature provides limited evidence on standardized diagnostic criteria, biological behavior, and optimal treatment strategies for this entity. We describe a 73‐year‐old Chinese woman with a two‐year history of a left nipple mass that developed erythema and ulceration five days prior to presentation. Imaging studies (ultrasonography and MRI) identified an isolated nipple lesion (BI‐RADS 4b) with no other breast tissue involvement. Wide local excision confirmed solid papillary carcinoma in situ (pTisN0M0), with pathological evaluation showing R0 resection margins. The patient received standard adjuvant endocrine therapy (letrozole 2.5 mg/day) and showed no evidence of recurrence at 9 month follow‐up. For patients with nipple‐confined solid papillary carcinoma lacking high‐risk features, complete surgical excision constitutes the mainstay of treatment, complemented by postoperative adjuvant endocrine therapy to mitigate recurrence risk.

Background MicroRNA (miRNA) expression in the brain is altered in neurodegenerative diseases. Recent studies demonstrated that selected miRNAs conventionally regulating gene expression at the post-transcriptional level can act extracellularly as signaling molecules. The identity of miRNA species serving as membrane receptor ligands involved in neuronal apoptosis in the central nervous system (CNS), as well as the miRNAs’ sequence and structure required for this mode of action remained largely unresolved. Methods Using a microarray-based screening approach we analyzed apoptotic cortical neurons of C56BL/6 mice and their supernatant with respect to alterations in miRNA expression/presence. HEK-Blue Toll-like receptor (TLR) 7/8 reporter cells, primary microglia and macrophages derived from human and mouse were employed to test the potential of the identified miRNAs released from apoptotic neurons to serve as signaling molecules for the RNA-sensing receptors. Biophysical and bioinformatical approaches, as well as immunoassays and sequential microscopy were used to analyze the interaction between candidate miRNA and TLR. Immunocytochemical and -histochemical analyses of murine CNS cultures and adult mice intrathecally injected with miRNAs, respectively, were performed to evaluate the impact of miRNA-induced TLR activation on neuronal survival and microglial activation. Results We identified a specific pattern of miRNAs released from apoptotic cortical neurons that activate TLR7 and/or TLR8, depending on sequence and species. Exposure of microglia and macrophages to certain miRNA classes released from apoptotic neurons resulted in the sequence-specific production of distinct cytokines/chemokines and increased phagocytic activity. Out of those miRNAs miR-100-5p and miR-298-5p, which have consistently been linked to neurodegenerative diseases, entered microglia, located to their endosomes, and directly bound to human TLR8. The miRNA-TLR interaction required novel sequence features, but no specific structure formation of mature miRNA. As a consequence of miR-100-5p- and miR-298-5p-induced TLR activation, cortical neurons underwent cell-autonomous apoptosis. Presence of miR-100-5p and miR-298-5p in cerebrospinal fluid led to neurodegeneration and microglial accumulation in the murine cerebral cortex through TLR7 signaling. Conclusion Our data demonstrate that specific miRNAs are released from apoptotic cortical neurons, serve as endogenous TLR7/8 ligands, and thereby trigger further neuronal apoptosis in the CNS. Our findings underline the recently discovered role of miRNAs as extracellular signaling molecules, particularly in the context of neurodegeneration.

Background Dysregulation of microRNA (miRNA) expression in the brain is a common feature of neurodegenerative diseases. Beyond their conventional role in regulating gene expression at the post-transcriptional level, certain miRNAs can act extracellularly as signaling molecules. Our study elucidates the identity of such miRNA species serving as ligands for membrane receptors expressed in central nervous system (CNS) neurons and the impact of such miRNAs on neurons in the context of neurodegenerative disease. Methods We combined a machine learning approach with the analysis of disease-associated miRNA databases to predict Alzheimer’s disease (AD)-associated miRNAs as potential signaling molecules for single-stranded RNA-sensing Toll-like receptors (TLRs) 7 and 8. TLR-expressing HEK-Blue reporter cells, primary murine microglia, and human THP-1 macrophages were used to validate the AD miRNAs as ligands for human and mouse TLR7 and/or TLR8. Interaction between mouse cortical neurons and extracellularly applied AD miRNAs was analyzed by live cell imaging and confocal microscopy. Transcriptome changes in cortical neurons exposed to AD miRNAs were assessed by RNAseq and RT-qPCR. The extracellular AD miRNAs’ effects on CNS neuron structure were investigated in cell cultures of murine primary cortical neurons and iPSC-derived human cortical neurons by immunocytochemistry. We employed a mouse model of intrathecal injection to assess effects of AD miRNAs acting as signaling molecules on neurons in vivo. Results We identified the AD-associated miRNAs miR-124-5p, miR-92a-1-5p, miR-9-5p, and miR-501-3p as novel endogenous ligands for TLR7 and/or TLR8. These miRNAs being extracellularly stable and active were taken up by murine cortical neurons via endocytosis and induced changes in neuronal inflammation-, proliferation-, and apoptosis-related gene expression. Exposure of both murine and human cortical neurons to the AD-associated miRNAs led to alterations of dendrite and axon structure, synapse protein expression, and cell viability in a sequence-dependent fashion. Extracellular introduction of the AD miRNAs into the cerebrospinal fluid of mice resulted in both changes in neuronal structure and synapses, and neuronal loss in the cerebral cortex. Most of the observed extracellular miRNA-induced effects on cortical neurons involved TLR7/8 signaling. Conclusion Neurodegenerative disease-associated miRNAs in extracellular form act as signaling molecules for CNS neurons including human cortical neurons, thereby modulating their structure and viability.

Breast cancer remains one of the foremost global health concerns, highlighting the urgent need for innovative diagnostic and therapeutic strategies. Traditional imaging techniques, such as mammography and ultrasound, play essential roles in clinical practice; however, they often fall short in detecting early-stage tumors and providing comprehensive insights into the mechanical properties of cancer cells. In this context, Atomic Force Microscopy (AFM) has emerged as a transformative tool in breast cancer research, owing to its high-resolution imaging capabilities and nanomechanical characterization. This review explores recent advancements in AFM technology as applied to breast cancer research, emphasizing key findings that include the differentiation of various stages of tumor progression through high-resolution imaging, precise characterization of mechanical properties, and the capability for single-cell analysis. These capabilities not only enhance our understanding of tumor heterogeneity but also reveal potential biomarkers for early detection and therapeutic targets. Furthermore, the review critically examines several challenges and limitations associated with the application of AFM in breast cancer research. Issues such as complexities in sample preparation, accessibility, and the cost of AFM technology are discussed. Despite these challenges, the potential of AFM to transform our understanding of breast cancer biology is significant. Looking ahead, continued advancements in AFM technology promise to deepen our insights into breast cancer biology and guide innovative therapeutic strategies aimed at improving patient outcomes.

Gut microbiota generally undergoes dynamic remodeling in concert with multifaceted self‐regulation of amphibian hosts during key life stages, such as metamorphosis and hibernation. However, the spatiotemporal dynamics of amphibian gut microbiomes across the lifecycle remain poorly understood. In this study, we applied 16S rRNA gene amplicon sequencing to characterize the gut microbiomes of cultivated Black‐spotted frog (Pelophylax nigromaculatus) across seasons. The gut microbiomes exhibited tissue‐specific succession, and structural discrepancies between gut regions fluctuated temporally. Both small‐ and large‐intestine microbiomes showed temporal decay patterns in abundance‐unweighted intercommunity indices, but not in abundance‐weighted indices. Compared with large‐intestine microbiomes, small‐intestine microbiomes were more randomized yet more centralized in terms of amplicon sequence variants, particularly within Proteobacteria (especially Pseudomonas). The alpha diversity of small‐intestine microbiomes was comparatively lower, and their taxonomic composition was more stable over time. We further elucidated the assembly mechanisms of gut microbiomes by systematically analyzing dominant driving factors, ecological processes, phylogenetic traits, source‐sink relationships, and co‐occurrence networks. Stochastic processes played a dominant role in gut microbiome assembly, while deterministic processes (e.g., habitat filtering and microbial interaction) contributed more strongly to large gut microbiomes than to small gut microbiomes. Overall, this study provides insights into the ecological dynamics and assembly mechanisms of amphibian gut microbiomes across the lifecycle and may inform targeted microbiome modification for amphibian breeding and conservation. Amphibian gut microbiomes exhibit a temporal‐decay pattern in abundance‐unweighted intercommunity indices rather than abundance‐weighted indices. Stochastic processes play a dominant role in the gut microbiome assembly. Deterministic processes contribute more to large‐intestine microbiomes than to small‐intestine microbiomes.

In this study, we modified microcrystalline cellulose by cross-linking it with epichlorohydrin to obtain a rapid and efficient adsorbent for the removal of Reactive Blue 4 dye from aqueous solution. Evidences of the cross-linking of the microcrystalline cellulose were obtained by Fourier transform infrared spectroscopy, X-ray diffraction, Brunauer–Emmett–Teller analysis, thermogravimetric analysis, and scanning electron microscopy. We investigated the effects of adsorbent dosage, pH, initial dye concentration, temperature, and contact time on the dye adsorption capacity. The results showed that the adsorption equilibrium time was just 20 min and the maximum adsorption capacity was 69.79 mg/g. The adsorption isotherm data fitted the Langmuir isotherm model well, and the adsorption kinetics data followed the pseudo-second-order kinetic model. The results of the thermodynamic analysis suggest that the adsorption process was spontaneous and exothermic. Recyclability experiments demonstrated the good reusability of this adsorbent. Electrostatic interaction was found to dominate the adsorption process.

The North China Craton (NCC) is the best example of an Archean craton that has lost its stability in the Late Mesozoic. Although the cratonic destruction is generally considered to have occurred in the Eastern Block and reached a peak in the Early Cretaceous, the exact areal extent of cratonic destruction is debated, especially the southern and northern margin of the NCC. Here we report geochronology, geochemical and Hf isotopic data of the Late Mesozoic granitoids from Lushi polymetal mineralization area (LPMA) in the southern margin of NCC. These results provide new insights into the destruction in the southern margin of the NCC during the Late Mesozoic. Zircon U-Pb dating indicates that eight granitoids intruded in the Late Jurassic to Early Cretaceous (136.8–154.1 Ma), respectively. Geochemical signatures define these granitoids being A-type or I-type granite that formed in an extension setting. In addition, Hf isotopic compositions of zircons from these granitoids vary in a relatively large range, with εHf(t) values and TDM2 ages ranginge from -26.1 to +15.2 and 215 to 2 849 Ma, respectively. The parental magmas were likely derived from diverse sources, including materials of the partial melting of ancient lower crust and mantle-derived mafic magmas in various proportions. Combining with previous studies on the contemporaneous magma-tectonic activities in circum of NCC, we suggest that the rim of NCC was already unstabilized from the Late Jurassic in the LPMA. The subduction of the Paleo-Pacific Plate was the main trigger to the destruction of the southern margin of NCC, which was responsible for the lithospheric extension and thinning, extensive magmatism and mineralization.

In order to investigate the oncogenic mechanisms of lung adenocarcinoma (LUAD), hub genes can be identified by constructing co-expression networks, and the potential linkages between hub genes, transcription factors (TFs) and microRNAs (miRNAs/miRs) can be visualized and identified. In the present study, a total of 12 co-expressed modules were constructed, and 9 of these were significantly correlated with clinical traits in LUAD. The differentially expressed genes and differentially expressed miRNAs were determined, and the targets of differentially expressed miRNA were identified from the hub genes or TFs. The results of the present study demonstrated that 10 hub genes and 12 TFs are the predicted targets for the 5 and 8 differentially expressed miRNAs, respectively. Genes in pink and red modules, which have a high correlation with the clinical trait of days to death, are significantly enriched in 'nucleosome assembly' and 'microtubule-based process', respectively. These results indicated that miR-206, miR-137, miR-153, hub genes and enriched TFs in the pink and red modules exert a potentially pivotal function in the development of LUAD.