The endoplasmic reticulum (ER) and mitochondria are critical organelles in maintaining cellular homeostasis and regulating cell fate. However, current biological and chemical approaches for modulating ER and mitochondrial functions often lack specificity and spatiotemporal controllability, potentially leading to off-target or systemic effects that limit their clinical applications. Here, by synthesizing a physical stimulus-based acoustoelectric nanoregulator, barium zirconate titanate (BZT) nanoparticles (NPs) with enhanced piezoelectric properties, we aimed to modulate ER and mitochondrial functions by regulating intracellular concentrations of calcium ions (Ca2+) and hydrogen ions (H+), thereby enabling spatiotemporally controllable modulation of cell fate. BZT NPs significantly modulated calcium ion dynamics and pH in tumor cells under ultrasound stimulation, accompanied by perturbations in ER and mitochondrial homeostasis, induction of ER stress and mitophagy, and ultimately alterations in cell fate. In the tumor-bearing mouse model, the acoustoelectric nanoregulator spatiotemporally modulates the intracellular environment through electrical signaling and ionic dynamic modulation under ultrasound stimulation, expanding the application prospects of physical stimulation-based strategies for abnormal cell function regulation. Our findings provide fresh perspectives for understanding cellular stress responses and cell fate determination processes, and lay the foundation for developing novel interventions in precision therapy and cell engineering applications.
Aim: To trace the historical evolution of hospital nursing centrism in China (1835-present) and examine how institutional path dependence has shaped the subordinate status of nursing within a doctor-dominated healthcare system. Background/introduction: Despite major expansions in nursing education and policy advocacy, China's nursing profession remains structurally marginalized. Understanding the roots of this subordination requires a historical and institutional lens. Methods: Drawing on path dependence theory, this study analyzes five critical phases in the development of nursing in China from 1835 to the present. A four-dimensional analytical framework that encompasses professional, organizational, fiscal, and governance institutions was applied to archival records, policy documents, academic studies, and interview data. Results or findings: Findings reveal that nursing has been persistently embedded in a "doctor-led, nurse-subordinate" governance structure. Although educational and legislative reforms expanded nursing's professional scope, entrenched institutional arrangements across the four dimensions have locked nursing into a structurally dependent position. Discussion: The historical institutionalization of nursing as an auxiliary role has limited its professional identity, participation in governance, and access to resources. The analysis highlights the limitations of reforms focused solely on education and policy without restructuring governance mechanisms. Conclusion: The professional development of nursing in China has been constrained by enduring path-dependent forces. To achieve true professionalization, reforms must address deep-seated institutional logics. Implications for nursing and nursing policy: Professional empowerment requires the redesign of nursing roles, decision-making power, and career pathways within hospital governance. Policy reforms should dismantle hierarchical governance structures and institutionalize nurses' participation in leadership, ensuring equitable distribution of authority and resources.
Cell survival and death are the fundamental biological processes of life that involve both intracellular and extracellular dynamic events. How cells balance survival and death determines cell fate, and this question has attracted extensive research interest for decades yet remains largely unresolved. This review focuses on BRUCE, the only essential inhibitor-of-apoptosis (IAP) protein for survival. Based on recent structural discoveries regarding the autophagy–apoptosis switch, we provide novel mechanistic insights into this long-standing scientific question. BRUCE possesses a distinctive structure: its C-terminal UBC domain confers Ub conjugase (E2) and Ub-protein ligase (E3) activities, while its N-terminal region contains a baculoviral IAP repeat (BIR) domain. Benefiting from such distinctive structural properties. BRUCE centrally governs cell fate by modulating the transition from autophagy to apoptosis and maintaining genomic stability. At the organismal level, BRUCE sustains the homeostasis of reproductive and developmental processes by either inhibiting apoptosis or mediating substrate degradation. Aberrant BRUCE upregulation is widely implicated in diverse pathologies, including neurodevelopmental disorders and multiple malignancies. Nevertheless, research focusing on the targeted inhibition of BRUCE remains largely underexplored. A better understanding of the structural features and functional mechanisms of BRUCE will help elucidate how it exerts its pathogenic effects via regulation of cell survival and death. Such insights will lay a solid foundation for the future discovery and therapeutic application of specific BRUCE-targeted inhibitors. Outlooks and perspectives on the associated challenges are provided as well.
Maintenance of the genome and epigenome stability is vital for animal longevity. Long noncoding RNAs, roX1 and roX2, are known to be important in the male X chromosome dosage complex in Drosophila males. However, their functions in Drosophila females have never been explored. This study demonstrates a role of roX RNAs in promoting heterochromatin formation in intestinal stem cells (ISCs) of Drosophila females under pathogen infection or aging. Increased heterochromatin formation in ISCs and progenitor enteroblasts (EBs) is associated with decreased active epigenetic modifications and global gene repression. Elevation of roX RNAs in ISCs promotes heterochromatinization and represses gene expression by recruiting heterochromatin proteins such as HP1a and Su(var)3-9. Overexpression of roX RNAs promotes ISCs hyperplasia, while their inactivation mitigates ISCs dysplasia and extends lifespan. Moreover, Xist RNA, the functional analog of roX RNAs, also promotes heterochromatin formation and ISCs hyperplasia in Drosophila, and significantly increases in aged people. Therefore, our findings reveal a role of roX RNAs in promoting heterochromatin expansion and controlling animal longevity.
The biogenesis and transport of lipoproteins are essential for systemic homeostasis and cardiometabolic health, yet how the secretory pathway acquires specialization to support high-capacity lipoprotein export remains unclear. Here, we report SEC16B as a tissue-selective modulator of the COPII machinery, critical for the efficient secretion of APOB-containing lipoproteins. Integrative bioinformatic analyses identify that SEC16B co-emerges with core genes involved in lipoprotein biogenesis. Functional studies, coupled with AI-driven prediction, reveal that SEC16B acts as a molecular brake to fine-tune COPII condensation for lipoprotein export. Mining of UK biobank data links SEC16B to metabolic traits in humans and suggests HNF4A-dependent regulation of SEC16B expression. Hepatic deletion of SEC16B in mice markedly reduces circulating APOB, triglycerides and cholesterol, while conferring robust protection against atherosclerosis and cardiac dysfunction and maintaining liver health. Collectively, these findings position SEC16B as a specialized modulator of lipoprotein export via the general secretory (SEC) pathway in the liver, suggesting potential therapeutic avenues for combating cardiometabolic diseases.
