In recent years, the rapid development of digital intelligence has provided a new path for rare disease data sharing and injected new power into the progress of research of rare diseases. This research is aimed at summarizing and consolidating relevant literatures on data sharing driven by digital intelligence (DI) in China and abroad, and constructing a local theoretical framework of DI-driven data sharing for rare diseases based on the status of rare diseases in China. Searching PubMed, EMbase, Cochrane, CNKI, Wanfang, and VIP database, we obtain a total of 214 representative literatures. Through literature review, we find that DI technologies have played important roles in different aspects of rare disease data sharing. China, the United States, and Europe have formed their own DI-driven data sharing systems for rare disease. From the theory of " Information Commons", we analyze the gap between China′s current situation and the goal of a " Rare Disease Data Commons". Based on the analysis, we put forward the idea of framework of " DI-STARS". China should develop the Data Sharing system making DI as the core of the system. Meanwhile, China should strengthen the data standardization system, create an innovation-encouraging environment, and build a bridge between different platforms. Using the DI-STARS theory, China will be able to build the " Rare Disease Data Commons" so that the diagnosis and treatment of rare diseases will be enhanced in China to meet the patients′ needs.

Dendrobium officinale(DO) is a traditional Chinese medicinal and edible plant, while it is critically endangered worldwide. This article, primarily based on the original research findings of the author's team and available articles, provides a comprehensive overview of the factors contributing to the endangerment of DO and the key technologies for the conservation, efficient cultivation, and value-added utilization of this plant. The scarcity of wild populations, low seed-setting rates, lack of endosperm in seeds, and the need for symbiosis with endophytic fungi for seed germination under natural conditions are identified as the primary causes for the rarity and endangerment of DO. Artificial seed production and tissue culture are highlighted as key technologies for alleviating the endangered status. The physiological and ecological mechanisms underlying the adaptation of DO to epiphytic growth are explored, and it is proposed that breaking the coupling of high temperature and high humidity is essential for preventing southern blight, a devastating affliction of DO. The roles of endophytic fungi in promoting the growth, improving the quality, and enhancing the stress resistance of DO are discussed. Furthermore, the integration of variety breeding, environment selection, and co-culture with endophytic fungi is emphasized as a crucial approach for efficient cultivation. The value-added applications of DO in pharmaceuticals, health foods, food products, and daily chemicals-particularly in the food and daily chemical industries-are presented as key drivers for a 10-billion-RMB-level industry. This systematic review offers valuable insights for the further development, utilization, and industrialization of DO resources, as well as for the broader application of conservation strategies for other rare and endangered plant species.
Dendrobium/microbiology* ; Endangered Species ; Seeds/microbiology* ; Fungi/physiology*

The primary cilium is a microtubule-based organelle that projects from the cell surface. It is present in cells from single-celled eukaryotes to vertebrates, including humans. Recent studies have found that primary cilia are also widely distributed in multiple organs and tissues of the reproductive system, where they influence reproductive function by directly participating in or indirectly regulating related signaling pathways, thereby affecting fertility. Primary cilia participate in the regulation of oocyte meiosis and development. They also influence sperm maturation by regulating the homeostatic microenvironment required for spermiogenesis. By mediating Hedgehog (Hh) and Wnt signaling pathways, primary cilia regulate endometrial receptivity and decidual response, thereby influencing the embryo implantation rate. Furthermore, primary cilia control the migration, invasion, differentiation, and vascular remodeling of human chorionic villi mesenchymal stromal cells and trophoblasts. Structural or functional impairment of primary cilia may disrupt placental vascular remodeling, leading to placental hypoplasia, potentially through the downregulation of downstream target genes of the Hh signaling pathway. Moreover, primary cilia may be involved in ovarian aging, ovulation, and endocrine function. This article reviews the research progress on the relationship between primary cilia and fertility, explores the potential mechanisms underlying roles of primary cilia in gamete development, endometrial receptivity, decidualization, placental development, and ovarian reproductive endocrine function, and aims to provide new insights for fertility preservation and the prevention and treatment of human reproductive disorders.

Osteosarcoma (OS), chondrosarcoma (CS), and Ewing sarcoma (ES) represent primary malignant bone tumors and pose significant challenges in oncology research and clinical management. Conventional research methods, such as two-dimensional (2D) cultured tumor cells and animal models, have limitations in recapitulating the complex tumor microenvironment (TME) and often fail to translate into effective clinical treatments. The advancement of three-dimensional (3D) culture technology has revolutionized the field by enabling the development of in vitro constructed bone tumor models that closely mimic the in vivo TME. These models provide powerful tools for investigating tumor biology, assessing therapeutic responses, and advancing personalized medicine. This comprehensive review summarizes the recent advancements in research on 3D tumor models constructed in vitro for OS, CS, and ES. We discuss the various techniques employed in model construction, their applications, and the challenges and future directions in this field. The integration of advanced technologies and the incorporation of additional cell types hold promise for the development of more sophisticated and physiologically relevant models. As research in this field continues to evolve, we anticipate that these models will play an increasingly crucial role in unraveling the complexities of malignant bone tumors and accelerating the development of novel therapeutic strategies.
Bone Neoplasms/pathology* ; Humans ; Osteosarcoma/pathology* ; Tumor Microenvironment ; Sarcoma, Ewing/pathology* ; Chondrosarcoma/pathology* ; Animals ; Cell Culture Techniques/methods* ; Cell Culture Techniques, Three Dimensional/methods* ; Cell Line, Tumor

OBJECTIVE: Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR). METHODS: We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes. RESULTS: Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk. CONCLUSIONS This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Humans ; Male ; East Asian People/genetics* ; Europe ; Gastrointestinal Microbiome ; Lung ; Macrophage Migration-Inhibitory Factors/metabolism* ; Mendelian Randomization Analysis ; Multiomics ; Pneumoconiosis/microbiology* ; Intramolecular Oxidoreductases

OBJECTIVES: To investigate the expression of cartilage acidic protein 1 (CRTAC1) in gastric cancer (GC) and its effect on biological behaviors and immune cell infiltration of GC. METHODS: Transcriptomic, GO and KEGG analyses were conducted to investigate the association of CRTAC1 expression with prognosis of GC patients and its involvement in cell function and signaling pathways. ESTIMATE algorithm was used to analyze the effect of CRTAC1 expression on the tumor microenvironment and the tumor mutation load. In two GC cell clines (HGC-27 and MKN-74), CCK8, EdU and clone formation assays, flow cytometry, and Hoechst staining were used to examine the effects of CRTAC1 knockdown on cell proliferation, cell cycle changes and apoptosis. Wound healing assay, Transwell assay, and Western blotting were performed to analyze the effect of CRTAC1 knockdown on GC cell migration and the underlying mechanism. RESULTS: Bioinformatics analysis showed significantly higher expression of CRTAC1 in GC tissues than in adjacent tissues (P<0.05). Age and tumor stage were both prognostic risk factors in GC patients with high CRTAC1 expression (P<0.001). Analysis using ESTIMATE algorithm showed that CRTAC1 expression increased immune cell infiltration and decreased tumor mutational load in GC (P<0.001). In HGC-27 and MKN-74 cells, CRTAC1 knockdown significantly inhibited cell proliferation and migration and promoted cell apoptosis. Western blotting demonstrated that CRTAC1 knockdown significantly increased E-cadherin expression and reduced the expression levels of vimentin, p-PI3K, AKT2, p-AKT and p-mTOR in GC cells. CONCLUSIONS High expression of CRTAC1 in GC tissues affects immunotherapeutic efficacy and prognosis of the patients, possibly by promoting epithelial-mesenchymal transition via modulating tumor mutational load, tumor microenvironment, and the PI3K/AKT signaling pathway.
Stomach Neoplasms/metabolism* ; Humans ; Cell Proliferation ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction ; Cell Movement ; Cell Line, Tumor ; Prognosis ; Apoptosis ; Tumor Microenvironment ; Female ; Male ; Epithelial-Mesenchymal Transition/genetics*

Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications. However, administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system (MPS). In this study, we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues. The fabricated nanoparticles (TM-CQ/NPs) were coated with fibroblast cell membrane expressing tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages, but increased the nanoparticle uptake in tumor cells. Importantly, this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors. Meanwhile, the encapsulated chloroquine (CQ) further suppressed the uptake of nanoparticles by macrophages, and synergized with TRAIL to induce tumor cell apoptosis. The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy. Together, our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.

Lipophagy, the selective engulfment of lipid droplets (LDs) by autophagosomes for lysosomal degradation, is critical to lipid and energy homeostasis. Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes. This function of ORP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs. Upon lipophagy induction, ORP8 has increased localization on LDs and is phosphorylated by AMPK, thereby enhancing its affinity for LC3/GABARAPs. Deletion of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular triglyceride. Overexpression of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice, and Osbpl8-/- mice exhibit liver lipid clearance defects. Our results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.
Animals ; Mice ; Lipid Droplets ; Autophagy ; Autophagosomes ; Homeostasis ; Triglycerides

Humans ; Blast Crisis/genetics* ; Leukemia, Promyelocytic, Acute/genetics* ; Oncogene Proteins, Fusion/genetics* ; Tretinoin

The finite element method is a new method to study the mechanism of brain injury caused by blunt instruments. But it is not easy to be applied because of its technology barrier of time-consuming and strong professionalism. In this study, a rapid and quantitative evaluation method was investigated to analyze the craniocerebral injury induced by blunt sticks based on convolutional neural network and finite element method. The velocity curve of stick struck and the maximum principal strain of brain tissue (cerebrum, corpus callosum, cerebellum and brainstem) from the finite element simulation were used as the input and output parameters of the convolutional neural network The convolutional neural network was trained and optimized by using the 10-fold cross-validation method. The Mean Absolute Error (MAE), Mean Square Error (MSE), and Goodness of Fit ( R ²) of the finally selected convolutional neural network model for the prediction of the maximum principal strain of the cerebrum were 0.084, 0.014, and 0.92, respectively. The predicted results of the maximum principal strain of the corpus callosum were 0.062, 0.007, 0.90, respectively. The predicted results of the maximum principal strain of the cerebellum and brainstem were 0.075, 0.011, and 0.94, respectively. These results show that the research and development of the deep convolutional neural network can quickly and accurately assess the local brain injury caused by the sticks blow, and have important application value for understanding the quantitative evaluation and the brain injury caused by the sticks struck. At the same time, this technology improves the computational efficiency and can provide a basis reference for transforming the current acceleration-based brain injury research into a focus on local brain injury research.
Brain ; Brain Injuries ; Computer Simulation ; Finite Element Analysis ; Humans ; Neural Networks, Computer