Periodontitis is a common oral disease caused by bacteria coupled with an excessive host immune response. Stem cell therapy can be a promising treatment strategy for periodontitis, but the relevant mechanism is complicated. This study aimed to explore the therapeutic potential of mitochondria from human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) for the treatment of periodontitis. The gingival tissues of periodontitis patients are characterized by abnormal mitochondrial structure. Human gingival fibroblasts (HGFs) were exposed to 5 μg/mL lipopolysaccharide (LPS) for 24 h to establish a cell injury model. When treated with hESC-MSCs or mitochondria derived from hESC-MSCs, HGFs showed reduced expression of inflammatory genes, increased adenosine triphosphate (ATP) level, decreased reactive oxygen species (ROS) production, and enhanced mitochondrial function compared to the control. The average efficiency of isolated mitochondrial transfer by hESC-MSCs was determined to be 8.93%. Besides, a therapy of local mitochondrial injection in mice with LPS-induced periodontitis showed a reduction in inflammatory gene expression, as well as an increase in both the mitochondrial number and the aspect ratio in gingival tissues. In conclusion, our results indicate that mitochondria derived from hESC-MSCs can reduce the inflammatory response and improve mitochondrial function in HGFs, suggesting that the transfer of mitochondria between hESC-MSCs and HGFs serves as a potential mechanism underlying the therapeutic effect of stem cells.
Humans ; Gingiva/cytology* ; Fibroblasts/metabolism* ; Mitochondria/physiology* ; Mesenchymal Stem Cells/cytology* ; Animals ; Periodontitis/therapy* ; Mice ; Reactive Oxygen Species/metabolism* ; Inflammation ; Lipopolysaccharides ; Human Embryonic Stem Cells/cytology* ; Cells, Cultured ; Adenosine Triphosphate/metabolism* ; Male

The dysfunction of the lysosome and autophagy-lysosome system serves as a driving force for neurodegenerative diseases, metabolic disorders, inflammatory conditions, and other related diseases, closely influencing their onset and progression. Therefore, restoring the function of the lysosome or autophagy-lysosome system has become an increasingly crucial therapeutic strategy in disease management. In this review, we will introduce the lysosomal biogenesis, structure, and function, as well as the biological process of the autophagy-lysosome system. Various diseases closely associated with lysosomal/autophagic dysfunction are also reviewed, emphasizing the significance of targeting the function of the lysosome or autophagy-lysosome system in disease treatment. Finally, we focus on engineered nanomaterials that have the capabilities to restore the function of the lysosome or autophagy-lysosome system, and summarize different strategies and methods for achieving this goal. This review aims to elucidate the latest progress in the field of nanomedicine for lysosomal/autophagic defect-related diseases and inspire the development of innovative and clinically valuable nanomedicines.
Humans ; Lysosomes/physiology* ; Autophagy/physiology* ; Nanomedicine/methods* ; Neurodegenerative Diseases/therapy* ; Animals ; Nanostructures ; Lysosomal Storage Diseases/therapy*

Megakaryocytes and hepatocytes are unique cells in mammals that undergo polyploidization through endomitosis in terminal differentiation. Many polyploidization regulators and underlying mechanisms have been reported, most of which are tightly coupled with development, organogenesis, and cell differentiation. However, the nature of endomitosis, which involves successful entry into and exit from mitosis without complete cytokinesis, has not yet been fully elucidated. We highlight that endomitosis is a new cell fate in the cell cycle, and tetraploidy is a critical stage at the bifurcation of cell fate decision. This review summarizes the recent research progress in this area and provides novel insights into how cells manipulate mitosis toward endomitosis. Endomitotic cells can evade the tetraploidy restrictions and proceed to multiple rounds of the cell cycle. This knowledge not only deepens our understanding of endomitosis as a fundamental biological process but also offers new perspectives on the physiological and pathophysiological implications of polyploidization.
Hepatocytes/physiology* ; Megakaryocytes/physiology* ; Humans ; Polyploidy ; Animals ; Cell Cycle/physiology* ; Cell Differentiation ; Mitosis/physiology*

BACKGROUND: Periodontitis is characterized by alveolar bone resorption, aggravated by osteoblast dysfunction, and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2 (NRF2) level. We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation. METHODS: Primary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or other stimuli. Reactive oxygen species (ROS) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining were used to detect intracellular oxidative stress. Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts. Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase (MAPK) pathway and related molecule activities. Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1 (DUSP1) in cells. RESULTS: Ligated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples. Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation, whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate. NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression, thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts. The interaction between NRF2 and DUSP1 was observed. CONCLUSIONS: NRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway. These findings form the basis of periodontitis treatment.
Animals ; NF-E2-Related Factor 2/physiology* ; Lipopolysaccharides/pharmacology* ; Osteoblasts/drug effects* ; Mice ; Porphyromonas gingivalis/chemistry* ; Cell Differentiation ; Osteogenesis ; Dual Specificity Phosphatase 1/metabolism* ; Mandible/cytology* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Periodontitis/metabolism* ; Cells, Cultured ; Male ; Cell Nucleus/metabolism*

Chemical communication in plant-microbiome and intra-microbiome interactions weaves a complex network, critically shaping ecosystem stability and agricultural productivity. This non-contact interaction is driven by small-molecule signals that orchestrate crosstalk dynamics and beneficial association. Plants leverage these signals to distinguish between pathogens and beneficial microbes, dynamically modulate immune responses, and secrete exudates to recruit a beneficial microbiome, while microbes in turn influence plant nutrient acquisition and stress resilience. Such bidirectional chemical dialogues underpin nutrient cycling, co-evolution, microbiome assembly, and plant resistance. However, knowledge gaps persist regarding validating the key molecules involved in plant-microbe interactions. Interpreting chemical communication requires multi-omics integration to predict key information, genome editing and click chemistry to verify the function of biomolecules, and artificial intelligence (AI) models to improve resolution and accuracy. This review helps advance the understanding of chemical communication and provides theoretical support for agriculture to cope with food insecurity and climate challenges.
Microbiota/physiology* ; Plants/microbiology* ; Artificial Intelligence ; Ecosystem

Objective:The variability of the apnea-hypopnea index（AHI） measured in the first and second halves of the night is significant in patients with obstructive sleep apnea hypopnea syndrome（OSAHS）. This variation may be related to fluid redistribution caused by the supine position during sleep. Methods:Eighty-nine adult subjects were enrolled. Circumferences（neck, chest, waist, and calf） were measured before sleep onset and upon awakening. Polysomnography（PSG） was performed, and the night was divided into two halves based on the midpoint of total sleep time to calculate AHI for each half. The correlation between changes in AHI and changes in circumferences was analyzed. Results:Twenty simple snorers and sixty-nine OSAHS patients were included, with a median AHI of 22.6（11.8, 47.3） events/hour. Compared to pre-sleep measurements, there was no significant change in neck circumference upon awakening in the control group（P=0.073）, while reductions were observed in the other three measurements（P=0.006, P=0.038, P<0.001）. In the OSAHS group, neck circumference increased（P<0.001）, and reductions were noted in the other three measurements（P<0.001 for all）, with the most significant change observed in calf circumference 40.0（37.1, 42.0） cm to 38.0（35.8, 40.5） cm. Compared to the first half of the night, total AHI, supine AHI, and NREM AHI significantly decreased in the second half（P=0.010, P=0.031, P=0.001）, while no significant changes were observed in lateral AHI and REM AHI（P=0.988, P=0.530）. Further analysis revealed a significant relationship between increased chest circumference and decreases in NREM AHI, supine AHI, and supine NREM AHI（P=0.036, P=0.072, P=0.034）, as well as between decreased lateral position AHI and increased waist circumference（P=0.048）. Additionally, this study found a negative correlation between changes in calf circumference and changes in AHI（R=-0.24, P=0.048）, while neck circumference changes positively correlated with changes in AHI（R=0.26, P=0.03）. Conclusion:In OSAHS patients during the second half of sleep compared to before sleeping, chest circumference, waist circumference, and calf circumference decrease while neck circumference increases; total AHI, supine position AHI, and NREM period AHI decrease; increases in chest circumference are associated with decreases in NREM period AHI, supine position AHI, supine position NREM period AHI. There is nocturnal variability in AHI among OSAHS patients that may be associated with fluid shifts during sleep.
Humans ; Sleep Apnea, Obstructive/physiopathology* ; Male ; Female ; Polysomnography ; Fluid Shifts/physiology* ; Adult ; Middle Aged ; Neck ; Severity of Illness Index ; Sleep/physiology* ; Snoring/physiopathology*

Human taste is an important function of chemical perception. In recent years, brain taste evoked potentials have received more and more attention as a feasible tool for objective assessment of taste dysfunction. This paper reviews the main characteristics of gustatory evoked potential signals, the most widely used recording and processing techniques, and the scientific advances and relevance of gustatory evoked potentials in many important applications. In particular, taste evoked potentials are used to study the central effects of food intake and taste disorders, which may affect cognition and personality, or may be potential indicators of the onset or progression of neurological disorders. For these reasons, this paper presents and analyzes the latest scientific results and future challenges of using gustatory evoked potentials as an attractive solution to objective monitoring techniques for taste disorders. Human taste is an important function of chemical perception. In recent years, brain gustatory evoked potentials have received more and more attention as a feasible tool for objective assessment of taste dysfunction. This paper reviews the main characteristics of gustatory evoked potential signals, the most widely used recording and processing techniques, and the scientific advances and relevance of gustatory evoked potentials in many important applications. In particular, gustatory evoked potentials are used to study the central effects of food intake and taste disorders, which may affect cognition and personality, or may be potential indicators of the onset or progression of neurological disorders. For these reasons, this paper presents and analyzes the latest scientific results and future challenges of using gustatory evoked potentials as an attractive solution to objective monitoring techniques for taste disorders.
Humans ; Evoked Potentials ; Taste/physiology* ; Taste Perception/physiology*

Objective:To establish normal reference value ranges for dynamic balance function parameters in healthy Chinese adults aged 20-69 years. Methods:A total of 100 healthy subjects were selected and evenly divided into five age groups: 20-29, 30-39, 40-49, 50-59, and 60-69 years, with equal gender distribution in each group. Balance function was assessed using the EquiTest system （NeuroCom）, with following tests performed Sensory Organization Test （SOT）, Motor Control Test （MCT）, Adaptation Test （ADT）, and Limits of Stability （LOS） test. All parameters were statistically analyzed and expressed as ±S. Results:The normal reference ranges for SOT, MCT, ADT, and LOS parameters were established for each age group. Multiple balance function parameters demonstrated a gradual decline with advancing age, with more pronounced deterioration observed after the age of 60. Specific findings included decreased vestibular ratio and reduced visual preference in SOT, as well as prolonged reaction time, impaired directional control, and reduced maximum excursion in the backward direction during LOS testing. Conclusion:This study is the first to establish age-specific reference ranges for dynamic balance function parameters in a healthy Chinese population aged 20-69 years, providing localized and objective criteria for the assessment of balance function and supporting clinical diagnosis of balance-related disorders in China.
Humans ; Middle Aged ; Adult ; Postural Balance/physiology* ; Reference Values ; Aged ; Male ; Female ; Young Adult ; Healthy Volunteers

The circadian clock is a highly conserved timekeeping system in organisms, which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression. Substantial clinical and experimental evidence has established a close association between circadian rhythm disruption and the development of various malignancies. Research has revealed characteristic alterations in the circadian gene expression profiles in tumor tissues, primarily manifested as a dysfunction of core clock components (particularly circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1)) and the widespread dysregulation of their downstream target genes. Notably, CLOCK demonstrates non-canonical oncogenic functions, including epigenetic regulation via histone acetyltransferase activity and the circadian-independent modulation of cancer pathways. This review systematically elaborates on the oncogenic mechanisms mediated by CLOCK/BMAL1, encompassing multidimensional effects such as cell cycle control, DNA damage response, metabolic reprogramming, and tumor microenvironment (TME) remodeling. Regarding the therapeutic strategies, we focus on cutting-edge approaches such as chrononutritional interventions, chronopharmacological modulation, and treatment regimen optimization, along with a discussion of future perspectives. The research breakthroughs highlighted in this work not only deepen our understanding of the crucial role of circadian regulation in cancer biology but also provide novel insights for the development of chronotherapeutic oncology, particularly through targeting the non-canonical functions of circadian proteins to develop innovative anti-cancer strategies.
Humans ; ARNTL Transcription Factors/physiology* ; Neoplasms/therapy* ; CLOCK Proteins/physiology* ; Circadian Clocks/genetics* ; Animals ; Circadian Rhythm/genetics* ; Tumor Microenvironment ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic

Hippo signaling is a highly conserved pathway central to diverse cellular processes. Dysregulation of this pathway not only leads to developmental abnormalities but is also closely related to the occurrence and progression of various cancers. Recent studies have uncovered that, in addition to the classical signaling cascade regulation, biomolecular condensates formed via phase separation play a key role in the spatiotemporal regulation of Hippo signaling. In this review, we provide a summary of the latest research progress on the regulation of the Hippo signaling pathway by phase separation, with a particular focus on transcriptional activation mediated by Yes-associated protein (YAP)/transcriptional coactivator with post-synaptic density-95, disks-large, and zonula occludens-1 (PDZ)-binding domain (TAZ) condensates. Furthermore, we discuss the utility of chemical crosslinking combined with mass spectrometry to analyze the TAZ condensate interactome and examine the role of the protein fused in sarcoma (FUS) in modulating the biophysical properties of TAZ condensates, which in turn influence their transcriptional activity and pro-tumorigenic functions. These insights not only advance our understanding of Hippo signaling but also offer new perspectives for therapeutic interventions targeting diseases linked to dysregulated YAP/TAZ activity.
Humans ; Signal Transduction ; Hippo Signaling Pathway ; Protein Serine-Threonine Kinases/physiology* ; Animals ; Biomolecular Condensates/metabolism* ; Transcription Factors/metabolism* ; YAP-Signaling Proteins ; Adaptor Proteins, Signal Transducing/metabolism* ; Neoplasms ; Transcriptional Activation ; Intracellular Signaling Peptides and Proteins/metabolism*