Objective: To examine the causal association and potential mechanisms between bone mineral density in different age groups and primary malignant bone tumor based on two sample Mendelian randomization (MR), so as to provide a reference for the prevention and treatment of primary malignant bone tumor. Methods: The genome-wide association study (GWAS) of bone mineral density was obtained from the GEFOS database,which included 66 628 subjects divided into five age groups (0-15, 15-30, 30-45, 45-60, and >60 years) based on the phases of human bone development. The GWAS of primary malignant bone tumor was sourced from the FinnGen database, including 648 cases and 378 749 controls. Using bone mineral density of five age groups as the exposure and primary malignant bone tumor as the outcome, an MR analysis was performed with the inverse-variance weighted (IVW) method. Sensitivity analysis were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO test and MR Steiger test. The potential mechanisms underlying the causal association between bone density and primary malignant bone tumors were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: The MR analysis results showed that there was a negative causal association between bone density and primary malignant bone tumors in the 30-45 age group (OR=0.301, 95%CI: 0.126-0.721). No statistically significant associations between bone density and primary malignant bone tumors were found in the 0-15, 15-30, 45-60, and >60 age groups (all P>0.05). Sensitivity analysis did not detect heterogeneity, pleiotropy (all P>0.05) and reverse causality. KEGG enrichment analysis revealed that genes highly associated with bone density and primary malignant bone tumors were enriched in the mTOR signaling pathway and the Wnt signaling pathway, among which Low Density lipoprotein Receptor Related protein 5 and Wnt Family Member 16 are key regulatory genes. Conclusion The decrease in bone mineral density among individuals aged 30-45 may increase the risk of primary malignant bone tumors through the mTOR signaling pathway and the Wnt signaling pathway.

Current epilepsy prediction methods are not effective in characterizing the multi-domain features of complex long-term electroencephalogram (EEG) data, leading to suboptimal prediction performance. Therefore, this paper proposes a novel multi-scale sparse adaptive convolutional network based on multi-head attention mechanism (MS-SACN-MM) model to effectively characterize the multi-domain features. The model first preprocesses the EEG data, constructs multiple convolutional layers to effectively avoid information overload, and uses a multi-layer perceptron and multi-head attention mechanism to focus the network on critical pre-seizure features. Then, it adopts a focal loss training strategy to alleviate class imbalance and enhance the model's robustness. Experimental results show that on the publicly created dataset (CHB-MIT) by MIT and Boston Children's Hospital, the MS-SACN-MM model achieves a maximum accuracy of 0.999 for seizure prediction 10 ~ 15 minutes in advance. This demonstrates good predictive performance and holds significant importance for early intervention and intelligent clinical management of epilepsy patients.
Humans ; Electroencephalography/methods* ; Epilepsy/physiopathology* ; Neural Networks, Computer ; Seizures/physiopathology* ; Signal Processing, Computer-Assisted ; Algorithms

The aging microenvironment, as a key driver of tumorigenesis and progression, plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype (SASP). SASP consists of a variety of interleukins, chemokines, proteases, and growth factors. It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms, thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment. Furthermore, these secreted factors activate key signaling pathways such as NF-κB, cGAS-STING, and mTOR, which regulate the expression of immune-related molecules (such as PD-L1) and promote the recruitment of immunosuppressive cells, including regulatory T cells and myeloid-derived suppressor cells. This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment. Furthermore, the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms, including approaches to inhibit SASP secretion or eliminate senescent cells. Although these strategies have shown promise in certain tumor models, the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies. This highlights the need for further research into adaptive stratification and personalized treatment approaches. Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.

Dysfunction of the interoceptive system is recognized as an important component of clinical symptoms, including anxiety, depression, psychosis, and other mental disorders. Non-invasive neuromodulation is an emerging clinical intervention approach, and over the past decade, research on non-invasive neuromodulation aimed at regulating interoception has rapidly developed. This review first outlines the pathways of interoceptive signals and assessment methods, then summarizes the interoceptive abnormalities in psychiatric disorders and current studies for non-invasive neuromodulation targeting interoception, including intervention modes, target sites, interoceptive measures, and potential neurobiological mechanisms. Finally, we discuss significant research challenges and future directions.
Humans ; Interoception/physiology* ; Mental Disorders/therapy*

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In general, bioassay-guided fractionation and isolation of bioactive constituents from botanical materials frequently ended up with the reward of a single compound. However, botanical materials typically exert their therapeutic actions through multi-pathway effects due to the intrinsic complex nature of chemical constituents. In addition, the content of bioactive compounds in botanical materials is largely dependent on humidity, temperature, soil, especially geographical origins, from which rapid and accurate identification of plant materials is pressingly needed. These long-standing obstacles collectively impede the deep exploitation and application of these versatile natural sources. To address the challenges, a new paradigm integrating biogravimetric analyses and machine learning-driven origin classification (BAMLOC) was developed. The biogravimetric analyses are based on absolute qHNMR quantification and in vivo zebrafish model-assisted activity index calculation, by which bioactive substance groups jointly responsible for the bioactivities in all fractions are pinpointed before any isolation effort. To differentiate origin-different botanical materials varying in the content of bioactive substance groups, principal component analysis, linear discriminant analysis, and hierarchical cluster analysis in conjunction with supervised support vector machine are employed to classify and predict production areas based on the detection of volatile organic compounds by E-nose and GC-MS. Expanding BAMLOC to Codonopsis Radix enables the identification of polyacetylenes and pyrrolidine alkaloids as the bioactive substance group for immune restoration effect and accurately determines the origins of plants. This study advances the toolbox for the discovery of bioactive compounds from complex mixtures and lays a more definitive foundation for the in-depth utilization of botanical materials.

Objective: To investigate the causal association between amino acids and the primary malignant bone tumor and its underlying mechanism. Methods: Genome-wide association study (GWAS) data of glycine, serine, arginine, glutamine, methionine, and leucine was sourced from the IEU OpenGWAS database and the GWAS Catalog. GWAS data of primary malignant bone tumor were obtained from the FinnGen database. Using each of the six amino acids as the exposure and primary malignant bone tumor as the outcome, two-sample Mendelian randomization (MR) analysis was performed with the inverse-variance weighted method as the primary approach. Multivariable MR analysis was employed to control for collinearity among amino acids. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression and the MR Steiger test. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction network analysis were explored to explore potential mechanisms and identify key genes. Results: MR analysis results indicated a statistically significant causal association between glycine and primary malignant bone tumor (OR=1.719, 95%CI: 1.083-2.728). No significant causal associations were found for the other five amino acids (all P>0.05). Multivariable MR analysis revealed that, after adjusting for the other five amino acids, confirmed a positive causal association between glycine and primary malignant bone tumor (OR=1.512, 95%CI: 1.125-2.031). Sensitivity analyses revealed no significant heterogeneity, horizontal pleiotropy, or reverse causality (all P>0.05). Genes associated with both glycine metabolism and primary malignant bone tumor were enriched in the JAK-STAT signaling pathway, with serine hydroxymethyltransferase 2 (SHMT2) identified as a key gene. Conclusion Higher glycine levels may increase the risk of primary malignant bone tumor via the SHMT2-JAK-STAT pathway.

Objective: To constructCSF1R+/-mice and to analyze their genotypes, so as to provide animal model basis for disease pathological mechanism and drug target. Methods : A linearized targeting vector was designed according to Cre/Loxp system. A Loxp site was inserted upstream of the 5th exon of theCSF1Rgene, and a neomycin resistance box with Loxp sites on both sides was inserted downstream of the 5th exon. The linearized targeting vector was electroporated into embryonic stem cells. The correctly targeted embryonic stem cells were injected into the blastocysts of C57BL/6J mice to obtain chimeric mice, which were bred with Zp3-Cre mice. The newborn mice were numbered 9-14 days after birth and their tails were cut. The DNA of the mice was extracted, and the genotype of the mice was identified by polymerase chain reaction and agarose gel electrophoresis. The expression of CSF1R in mouse macrophages was detected by flow cytometry. The expression of CSF1R in mouse tissues was detected by Western blot. Results: The results of agarose gel electrophoresis showed that 453 bp bands were amplified in wild type mice, and 453 bp and 650 bp bands were amplified in heterozygous mice. The results of flow cytometry showed that the expression of CSF1R in peritoneal macrophages and bone marrow-derived macrophages of CSF1R heterozygous mice was lower than that of WT group(P<0.05). The results of Western blot showed that the expression of CSF1R in spleen, kidney and brain tissue of CSF1R heterozygous group was lower than that of WT group(P<0.05). Conclusion CSF1R+/-mice are successfully constructed, reproduced and identified, which provides an animal model basis for further revealing the potential mechanism of CSF1R in immune regulation.

The bone morphogenetic protein (BMP) family has numerous members that play various regulatory roles in cell differentiation and tissue morphogenesis. They can precisely regulate cell proliferation, differentiation, apoptosis, and other processes. Notably, the members of the BMP family, such as BMP1, BMP2, BMP4, and BMP7, etc., play significant roles in the odontoblast differentiation. By delving into the expression and regulatory mechanisms of BMP during tooth development and reparative regeneration, a deeper understanding of the biological processes involved in tooth formation can be gained, providing theoretical support for the repair and regeneration of dental defects. However, the clinical application of BMP still faces numerous challenges, and how to precisely regulate the expression and activity of BMP during odontogenic differentiation remains to be further studied. In this review, the research progress in the role of the BMP family members for odontogenic differentiation was summarized, with a view to providing some reference for exploring new therapeutic strategies of BMP application in the repair and regeneration of dental defect.

Purpose To investigate the clinicopathological features and molecular features of diffuse paediatric-type high-grade glioma,H3-wildtype and IDH-wildtype(pHGG H3/IDH WT)of central nervous system.Methods The clinical and pathological data of 6 cases of pHGG H3/IDH WT diagnosed by Department of Pathology,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine were retrospectively ana-lyzed.The expression of GFAP,Olig2,Syn,NeuN,IDH1,H3K27M was detected by immunohistochemistry(automatic im-munohistochemical staining device).The EGFR and MYCN gene amplification was detected by FISH.IDH,H3F3A and TERT gene mutations were detected by Sanger sequencing.The literatures were reviewed.Results The 6 patient's age ranged from 5 to 11 years,with a median age of 7.5 years.Among them,there were 2 males and 4 females,with a male to female ratio of 1∶2.The clinical symptoms were limb weakness,hemi-plegia,vomiting,convulsions,blurred vision and so on.Tumors were located in supratentorial brain for 5 cases and one in brain stem and cerebellum.Histologically,3 cases showed the mor-phological features of high-grade glioma,2 of which with giant cells.Two cases showed embryonal tumor-like features,and one had both high-grade glioma and embryonal tumor-like morpho-logical features.Microvascular proliferation and/or necrosis were present in 5 cases.Myxoid/microcystic stroma was found in 1 case.By immunohistochemistrically,the tumor cells were par-tially or focally positive for GFAP(6/6)and Olig2(6/6),fo-cally positive for Syn(3/6)and NeuN(1/6),and negative for IDH1,H3K27M,H3G34V and H3G34R.ATRX,H3K27me3,INI1 and BRG1 were diffusely positive(6/6).The positive rate of p53 was 5％-95％,and Ki67 proliferation index was 40％-90％.Molecular analysis showed that all 6 cases were IDH1/2 and H3F3A wild-type.MYCN amplification was observed in 2 cases.Two cases of EGFR amplification with polyploidy;one case had both EGFR amplification and MYCN amplification.PDGFRA amplification was observed in one case.For treatment and follow-up,the patients received postoperative radiotherapy and/or temozolomide chemotherapy;three patients died at 1 to 5 months after operation.Two patients survived and were followed up for 4 and 7 months,respectively.One patient was lost to fol-low-up.Conclusions pHGG H3/IDH WT is a highly malignant tumor with glioblastoma-like or embryonal tumor-like features.According to the molecular characteristics,it can be divided into three molecular subtypes,RTK1,RTK2 and MYCN.pHGG MYCN has the worst prognosis.Attention should be paid to the differential diagnosis of other pediatric or adult high-grade glio-mas and embryonal tumors.