To investigate the role of circular RNAs （circRNA） in Alzheimer’s disease （AD） and its potential mechanism.

Six-month-old APP/PS1 mouse model of AD and wild type (WT) mice were subjected and then randomly divided into WT group, WT+ circ-Olfm1 knockout group, AD group (transgenic APP/PS1 mice), AD+ circ-Olfm1 knockout group, AD+FOXO3a knockout group, with 3 mice in each group. ① The total RNA of mouse brain was extracted, and the differential expression of circRNAs and mRNAs between the AD mice and WT mice was detected, and the obtained circRNAs and mRNAs were analyzed with gene ontology (GO) analysis. ② RT-qPCR was used to detect the expression of the top 10 up-regulated and down-regulated circRNAs, as well as the expression of circ-Olfm1 and miR-330-5p. ③ Lentiviral vectors were prepared and stereotaxically injected into the cortex or hippocampus of WT and AD mice to knock out circ-Olfm1 gene. Water maze test was used to evaluate the effect of circ-Olfm1 knockout on cognitive function, and immunofluorescence assay was employed to observe the deposition of amyloid β (Aβ) plaque in the brain. ④ The interaction between circ-Olfm1 and miR-330-5p was verified by double luciferase reporter gene analysis. ⑤ The protein levels of AMPK and FOXO3a were detected by Western blotting. ⑥ Transmission electron microscopy was utilized to observe the mitochondria of the hippocampus. ⑦ The levels of inflammatory factors IL-6, IL-1β and TNF-α were detected by ELISA.

There were totally 52 differentially expressed circRNAs identified between the AD and WT mice, including 28 up-regulated and 24 down-regulated (fold change >1.5, P<0.05). These differentially expressed genes are mainly involved in signal transduction, learning and memory and other functions. circ-Olfm1 was identified as the most significantly differentially expressed circRNA, which is highly expressed in the neurons and up-regulated in the cerebral cortex and hippocampus of the AD mice. Knockout of circ-Olfm1 reduced the number of Aβ plaques in the cerebral cortex and hippocampus of AD mice (P<0.01). In starBase database, there are complementary sequences observed between circ-Olfm1 and miR-330-5p. Western blotting showed that the addition of Aβ42 significantly increased the expression of AMPK and FOXO3a in the neuronal cells (P<0.01). And silencing circ-Olfm1 led to decreased expression of AMPK and FOXO3a in neuronal cells+Aβ42 (P<0.01). ELISA revealed that knockout of FOXO3a significantly increased the levels of inflammatory factors IL-6, IL-1β, and TNF-α (P<0.01). Transmission electron microscopy displayed that knocking FOXO3a out significantly aggravated mitochondrial damage (P<0.01).

circ-Olfm1 is up-regulated in the brain tissue and neurons+Aβ42 of AD rats, and the mechanism of cognitive impairment in AD rats may be through its regulating FOXO3a protein.

To map the genome-wide distribution profile of histone H3K27me3 modification in diffuse gastric cancer tissues，identify target genes regulated by H3K27me3，and primarily explore the potential mechanism of its modification reprogramming in the occurrence and development of the tumor.

Normal gastric mucosal tissues and diffuse gastric cancer tissues were harvested from the patients who underwent examinations or treatments in the departments of gastroenterology and gastrointestinal surgery of our medical center between 2021 and 2023. There were 14 patients in the normal group （6 males and 8 females，average age of 46 years） and 14 patients in the gastric cancer group （8 males and 6 females，average age of 63 years）. Cleavage under target and tagmentation （CUT&Tag） technology was employed to capture genomic regions modified by H3K27me3，and analyze the reprogramming characteristics of these modifications. RNA sequencing data，data from high-throughput chromosome conformation capture （Hi-C） technology，and publicly available single-cell data were integrated to investigate the target genes regulated by the reprogramming of H3K27me3 modifications in diffuse gastric cancer cells.

The quality of the CUT&Tag and RNA sequencing data met the standards required for subsequent analysis. Histone H3K27me3 modifications in normal gastric mucosa and diffuse gastric cancer tissues were primarily distributed in distal intergenic regions and intronic regions. In gastric cancer tissues，compared to normal tissues，there was significant reprogramming of H3K27me3 modifications，characterized by a marked reduction in overall H3K27me3 signal intensity. The loss of 2 912 H3K27me3 signal peaks might lead to the up-regulation of 822 tumor-associated genes. Among them，56 genes displayed the most significant up-regulation （fold change in signal intensity ≥2，P<0.05），with notable enrichment in the mammalian target of rapamycin complex 1 （mTORC1） signaling pathway. Specifically，the methionine transporter SLC7A5 and the cystine transporter SLC7A11 were found to have the highest expression levels in gastric cancer tissues. Single-cell data revealed that the abnormal overexpression of SLC7A11 in diffuse gastric cancer was primarily observed in tumor epithelial cells. Further validation using public data and immunohistochemical experiments confirmed the elevated expression of SLC7A11 in diffuse gastric cancer，which is associated with poor prognosis in gastric cancer patients.

The reprogramming of histone H3K27me3 modification is an important epigenetic characteristic in diffuse gastric cancer. Loss of H3K27me3 signal peaks may up-regulate the expression of SLC7A11 in diffuse gastric cancer cells，and thereby promote tumor progression.

To investigate the underlying mechanism of abnormal specification of spermatogonial stem cells （SSCs） in male mice following Rb1 conditional knockout in mitotic-arrested prospermatogonia.

① R language was used to analyze the single-cell RNA sequencing （scRNA-seq） data of prospermatogonia derived from postnatal day 0.5 （P0.5） male mice through the gene expression omnibus （GEO） public database （accession number：GSE124904）. ② Mitoti-arrested prospermatogonia Rb1 conditional knockout （cKO） mice as well as Rb1 cKO mice with Id4-gfptransgene were generated using Vasa-Cre mice crossed with Rb1^flox/flox or Id4-gfp^Tg；Rb1^flox/flox mice. PCR was employed to detect the deletion of Rb1 in order todistinguish the control and cKOmale mice. The testes of male mice （n=3~8） within a few days after birth were collected. After that，flow cytometry was applied to divide the ID4-GFP cells into 3 communities based on the GFP fluorescence intensity，and then detect the number of cells and cell cycle in each community. ③ Germ cell proliferation （Ki67 positive，Ki67+），SSCs specification （FOXO1 nuclear transition），and germ cell differentiation （STRA8+） were detected with immunofluorescence staining. ④ TUNEL staining was utilized to detect cell apoptosis.

① The results of scRNA-seq showed that in the two set clusters of prospermatogonia，the prospermatogonia that further specifies to generate SSCs had enriched genes that are associated with cell proliferation. ② Germ cell proliferation assay indicated that the average ratio of Ki67+ germ cells in the testicular cross-section of the cKO mice was significantly higher than that of the control mice at P2.5 ［（46.10±6.21）% vs （11.22±3.27）%，P<0.01］. ③ Flow cytometry revealed that，among the brightest community of ID4-GFP cells，the percentage of the cells at S phase was obviously higher in the testicular cells derived from the cKO mice when compared to the control mice at P2.5 ［（12.05±1.22）% vs （5.05±1.46）%，P<0.05］.④ TUNEL staining displayed that cell apoptosis was detected in the testicular cross-section of cKO mice rather than that of the control mice. ⑤ The results of SSCs specification exploration showed that statistical difference was observed in the percentage of cytoplasmic FOXO1 in the testicular cross-section between the control and cKO mice ［（20.57±2.15）% vs （45.08±2.45）%，P<0.01］.

Rb1 knockout in mitotic-arrested prospermatogonia disrupts their postnatal cell cycle re-enter and induces cell apoptosis，which further results in abnormal SSC specification.

To construct a mammography image classification assistant system suitable for Chinese population，and explore the potential of artificial intelligence technology to assist early screening of breast cancer in China.

Curated breast imaging subset of digital database for screening mammography （CBIS-DDSM），Mammographic image analysis society database （MIAS） and other international open datasets were used to conduct model training respectively in order to reproduce the mainstream in-depth learning methods in the current literature. The model was also tested on the Chinese breast mammography database （CBMD） provided by Huajiao Technology Co.，Ltd，and the performance was compared. Aiming at the problem that the Chinese population data are not ideal in the performance test of the open dataset training model，an optimization strategy based on the sliding window adjustment mechanism was implemented in combination with the characteristics of Chinese population data. Then a two-stage migration learning method was designed to improve the overall performance of the model，and then development of our system was carried out.

With the sliding window adjustment mechanism and the CBMD training model after two-stage transfer learning，the accuracy of our developed system was improved from 0.50 of the open datasets to 0.80，precision from 0.54 to 0.82，sensitivity from 0.52 to 0.80，F1 value from 0.52 to 0.80，and AUC value from 0.51 to 0.89 based on the Chinese population dataset as the test set.

Through the introduction of sliding window adjustment mechanism and two-stage migration learning strategy，the performance of the breast molybdenum target image classification model has been significantly improved in the Chinese population dataset，and our system primarily achieves the purpose of assisting the classification of breast molybdenum target images for the Chinese population.