Advanced biology最新文献

Extracellular vesicles (EVs) are membrane-bound vesicles that are secreted by a wide range of organisms and cells, carrying cell-specific receptors and molecular cargo such as proteins and nucleic acids. EVs have emerged as promising biomarkers for cancer and neurodegenerative disorders like Alzheimer's Disease (AD). Traditional methods for isolating neuron-derived EVs from bodily fluids or conditioned media are based on bulk analysis methods, such as ultracentrifugation, isolation reagents, and immunoaffinity-based techniques, and lack spatial resolution to capture localized secretion dynamics. Here, our neurofluidic platform compartmentalizes neuronal networks and enables spatially resolved analysis of EV profiling before subsequent traditional isolation and content screening. This intermediate resolution provides critical insights into localized sub-neuronal EV secretion dynamics in cortical, hippocampal, and brainstem neurons. Using our platform, the influence of growth environment, cell maturation time, and exogenous stressors such as shear and biochemical stress can be unraveled. Biochemical stress is induced through okadaic acid (OA), a PP1A/PP2A inhibitor, which leads to hyperphosphorylation of proteins. In parallel, microRNA expression profiles are shown after OA treatment in primary neuron cultures, indicating an additional transcriptional response. These findings reveal regional differences in EV secretion dynamics associated with neuronal development and external stressors, including shear forces and PP1A/PP2A inhibition.

Barrier tissues—epithelial and endothelial interfaces that compartmentalize the human body—govern molecular exchange, immune surveillance, and organ homeostasis. Their dysfunction is central to disorders ranging from dermatitis to neurodegeneration. Conventional static cultures fail to capture the relevant microenvironment and typically rely on cell lines that overlook patient-specific genetics. Organs-on-chips (OoCs), by contrast, can recapitulate barrier-specific flow, biomechanics, chemical gradients, and a multicellular architecture. Additionally, incorporating primary or induced pluripotent stem cell (iPSC)-derived cells into OoCs can open new avenues for precision medicine. This review surveys the architectural diversity and physiological functions of human barrier systems and explores how OoC platforms—especially those using patient-derived cells—are advancing barrier disease modeling. It reveals similar core features but also unique barrier characteristics requiring specific adaptations, resulting in varied progress across systems, and continued refinement of iPSC differentiation protocols and OoC engineering is needed overall. Nevertheless, existing biological and technological advances already offer substantial, untapped opportunities to create physiologically relevant, patient-specific disease models and drug-testing platforms, bridging the gap between fundamental biology and translational medicine.

CDCA3 and TWIST1 are implicated in cell-cycle control and transcriptional regulation, yet their combined role in lung adenocarcinoma (LUAD) remains unclear. Here, we investigated the impact of the TWIST1/CDCA3 axis on LUAD cell behavior. Leveraging TCGA and KnockTF v2.0, we pinpointed TWIST1 as an upstream driver of CDCA3 in LUAD and delineated associated survival outcomes. ChIP and dual-luciferase assays verified the interaction between CDCA3 and TWIST1. We also quantified CDCA3 and TWIST1 mRNA by qRT-PCR and determined CDCA3, the immune-therapy biomarker PD-L1, and EMT-related protein levels by Western blot. Furthermore, CCK-8, colony formation assays, wound healing, and Transwell assays were conducted to evaluate the malignant behaviors of cells. Bioinformatic and functional analyses revealed that both CDCA3 and TWIST1 were highly expressed in LUAD, and their elevated levels predicted poor prognosis. Further investigation identified TWIST1 as an upstream activator of CDCA3. Knockdown of TWIST1 attenuated the malignant phenotype and reduced PD-L1 expression in LUAD cells, whereas subsequent overexpression of CDCA3 fully reversed these suppressive effects. This study aims to validate that the TWIST1/CDCA3 axis promotes invasion, migration, proliferation, and PD-L1 expression of LUAD cells.

Breast cancer bone metastasis often involves a prolonged dormancy phase, during which disseminated tumor cells (DTCs) remain undetectable and resistant to conventional therapies, posing a significant risk for late recurrence. Understanding the underlying mechanisms of tumor dormancy and reactivation is crucial for developing effective clinical interventions. However, current clinical translation faces multiple challenges, including limitations in detecting dormant tumor cells, insufficient biomarkers for dormancy, and difficulties in targeted drug delivery. Recent advances in elucidating the mechanisms of dormancy-such as the establishment of the pre-metastatic niche, intercellular communication in the bone marrow microenvironment, and signaling pathways regulating dormancy and reactivation-have provided novel therapeutic targets. Based on these mechanistic insights, nanotechnology-based drug delivery systems have emerged as promising strategies to precisely target dormant breast cancer cells in bone marrow niches. In this review, we summarize the current understanding of dormancy mechanisms in breast cancer bone metastasis, discuss the barriers hindering clinical translation, and highlight how mechanism-driven nanotherapeutic strategies may offer new opportunities to prevent recurrence by targeting dormant tumor cells.

Mosquitoes remain a significant global health concern due to their role in transmitting deadly diseases including malaria, dengue, and yellow fever. Recent advances in genetic modification technologies have enabled researchers to better study disease transmission and is an emerging approach for vector control. However, a major bottleneck is the need for continuous rearing of each new strain, an intensive process requiring substantial manual effort and space with inherent risks of cross-contamination, genetic drift, and catastrophic loss. Cryopreservation offers a potential solution, where strains could be stored indefinitely and revived on an as-needed basis. Here, we report a cryopreservation protocol that results in the recovery of viable Anopheles gambiae larvae. After thawing, 82% of larvae showed signs of viability, including wriggling and mouth brush movements. Approximately 15% further exhibited coordinated swimming behavior. Although post-thaw survival was limited to 24 h, this study provides the first evidence that mosquito larvae can survive cryopreservation, representing a key milestone toward long-term storage of mosquito lines.