OBJECTIVE：To investigate the mechanistic role of downregulating the differentially expressed protein c-Kit in glycidyl methacrylate (GMA)-induced premalignant transformation of 16HBE cells. METHODS：Three replicates of 16HBE cells were treated with 8 μg/mL GMA，and the same volume of dimethyl sulfoxide (DMSO) treatment served as a control group. The GMA- and DMSO-treated cells were passaged to the 10^th generation (P10) and then harvested. Real-time quantitative PCR (RT-qPCR) and Western blot experiments were performed to detect expression levels of c-Kit mRNA and protein in the two groups of cells. Following 24-hour treatment of GMA-treated cells with 5 and 20 μmol/L of the c-Kit-specific inhibitor ISCK03，western blot assay was performed to detect pathway-related proteins including PI3K，Akt，and their phosphorylation levels，as well as the expression levels of cycle-related proteins Cyclin D1 and Cyclin B1，and the apoptotic protein Caspase-3. Flow cytometry was employed to assess cell cycle progression and apoptotic changes across all groups. RESULTS：Compared with the DMSO control group，both c-Kit mRNA and protein expression levels were reduced in P10 cells treated with GMA (P<0.01). Following inhibition of c-Kit protein expression using 5 and 20 μmol/L ISCK03，compared to the GMA-treated group，the phosphorylation levels of PI3K and Akt proteins decreased，the expression levels of Cyclin B1 and Caspase-3 proteins declined，while the expression level of Cyclin D1 protein increased. Furthermore，cell cycle progression was impeded，and apoptosis rate was decreased，with all differences being statistically significant (all P<0.05). CONCLUSION：C-Kit protein may play an important role in the premalignant transformation of cells by regulating the cell cycle and apoptotic processes through inhibition of the PI3K/Akt signaling pathway. This study provides a reference for the mechanistic study of the potential carcinogenicity of GMA.

OBJECTIVE：To investigate contents and enrichment characteristics of key radioactive nuclides (uranium and thorium) in soil，wild plants，vegetables and water in a typical radiation sensitive area，as well as to explore their correlations. METHODS：Samples were collected from the surrounding area of a uranium mine in China. Concentrations of uranium and thorium in 47 samples of soil，plants，vegetables and water were detected by inductively coupled plasma mass spectrometry (ICP-MS). The contents，concentration ratio (CR) and correlations of uranium and thorium in soil，plants，vegetables and water at different sampling sites were analyzed. RESULTS：The contents of uranium and thorium in soil samples from 15 sampling sites were within the range of background values in the region. Their contents in vegetables and drinking water sources were within the limit values，and in foods were at a safe level. The CR values of moss in uranium and thorium were 0.966 and 1.228，respectively，which showed more prominent enrichment ability than other plants. There were significant correlations between uranium and thorium contents in plants/vegetables (P<0.01). CONCLUSION：This survey showed that the contents of uranium and thorium in the surrounding environment (soil，plants，vegetables，water) of the uranium mine were within the range of background values or food limits，and no pollution phenomenon was found. And moss with strong enrichment ability in this region was screened out，which could be used as a candidate plant for remediation of soil uranium pollution or indicator organism.

OBJECTIVE：To investigate whether Lycium barbarum polyphenols antagonize reproductive toxicity of benzophenone-3 (BP-3) by regulating the disulfide death process. METHODS：Databases including PubMed，CNKI，CTD，ChemicalBook，and PubChem were reviewed to retrieve core regulatory proteins of disulfidptosis，targets associated with BP-3-induced male genitourinary toxicity，and potential targets of major active components of Lycium barbarum polyphenols. Intersections of these target sets were identified using Venny 2.1.0. Common targets were imported into the STRING database to construct a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed via the DAVID database. A "major active components of Lycium barbarum polyphenols—common targets—pathways" network was built using Cytoscape 3.10.1. Molecular docking of BP-3 and major active components of Lycium barbarum polyphenols with common targets was conducted using AutoDock Vina to evaluate binding energies. RESULTS：A total of 75 targets related to BP-3-induced male genitourinary toxicity，160 potential targets of Lycium barbarum polyphenols' major active components，and 4 383 core disulfidptosis regulatory proteins were screened，yielding 9 common targets. Pharmacokinetic analysis indicated that morin，isorhamnetin，ferulic acid，p-coumaric acid，and cinnamic acid exhibited favorable intestinal absorption and drug-likeness. GO/KEGG enrichment analyses suggested that both BP-3 and Lycium barbarum polyphenols' major active components targeted the male genitourinary system. Network analysis revealed that key targets may play crucial roles in mitigating BP-3-induced damage by Lycium barbarum polyphenols' major active components. Molecular docking confirmed that BP-3 and these active components could bind near the active sites of PTGS2，ESR1，ESR2，and CYP1A1 via hydrogen bonds and other interactions，with strong binding energies. CONCLUSION：Major active components of Lycium barbarum polyphenols may alleviate BP-3-induced male genitourinary injury to a certain extent，and this antagonistic effect is likely mediated by key targets including PTGS2，ESR1，ESR2，and CYP1A1.

OBJECTIVE：Based on whole transcriptome sequencing and co-expression analysis，this study aimed to explore changes in non-coding RNA (ncRNA) expression profiles under chronic cobalt exposure to cerebral organoids and to investigate the role of competitive endogenous RNA (ceRNA) network in cobalt-induced neurotoxicity. METHODS：Mature cerebral organoids were continuously exposed to 0 and 20 μmol/L CoCl₂ for 28 days. Whole transcriptome sequencing was performed using the NovaSeq X Plus platform. Differential genes and differential ncRNAs between the control group and cobalt exposure group were identified with the screening thresholds of [log₂FC]≥1 and P_adjust<0.05，followed by gene ontology (GO) enrichment analysis. CeRNAs with potential interactions were screened according to Spearman correlation coefficient to construct a ceRNA network. Some RNAs in the network were verified by real-time quantitative PCR (RT-qPCR). RESULTS：A total of 2 968 differential genes，2 832 differential lncRNAs，82 differential miRNAs，and 35 differential circRNAs were identified by whole transcriptome sequencing. GO analysis showed that differential genes and target genes of differential ncRNAs were associated with metabolites and energy production，mainly including ATP biosynthesis，mitochondrial respiratory chain complex，and electron transport chain. Further verification using iPSC-derived neurons indicated that cobalt exposure could reduce intracellular ATP synthesis. Finally，a ceRNA regulatory network specific to the energy metabolism gene set was constructed，including 11 mRNAs，10 miRNAs，30 lncRNAs，and 2 circRNAs. RT-qPCR verification showed that the expression trends of PKM and miRNA 17_9658 were opposite，which was consistent with the sequencing results. CONCLUSION：Chronic cobalt exposure may induce neurotoxicity by affecting metabolic pathways，and the ceRNA regulatory network may play an important role in the neurotoxic mechanism of heavy metal cobalt.

OBJECTIVE：To use the transcriptome sequencing technology to investigate molecular mechanism of gallic acid (GA) against Burkitt lymphoma in vitro. METHODS：Inhibitory effect of GA on proliferation of human lymphoma Raji cells was assessed using the CCK-8 and PrestoBlue assays. Transcriptome sequencing technology was employed，combined with differential expression analysis，functional annotation，and pathway enrichment analysis，to decipher its mechanism of action. Key gene expression was validated by quantitative real-time PCR (RT-qPCR). RESULTS：Compared with the control group，both CCK-8 and PrestoBlue assays indicated that 50 and 100 μmol/L GA significantly inhibited the proliferation activity of Raji cells (P<0.05 or P<0.01). Transcriptomic analysis further revealed that GA exerted its anti-proliferation effects primarily by regulating the Fcγ receptor-mediated phagocytosis pathway. RT-qPCR results demonstrated that 100 μmol/L GA significantly suppressed the expression levels of key regulatory genes (VAV3，IGHG2，IGHV3-33) in this pathway (P<0.05 or P<0.01)，which was consistent with the transcriptome sequencing results. CONCLUSION：GA not only demonstrated direct cytotoxic effects but also enhanced the recognition and phagocytosis of tumor cells through modulation of tumor cell surface receptors.

OBJECTIVE：To investigate changes in expression of alcohol dehydrogenase 1A (ADH1A) and association with microvascular invasion (MVI)，the tumor immune microenvironment and prognosis as molecular mechanisms for hepatocellular carcinoma (HCC). METHODS：Using publicly available proteomic data from 101 HCC patients，ADH1A expression between tumor tissues and adjacent non-tumor tissues was compared. Based on the median ADH1A protein expression level，patients were divided into high and low expression groups. Survival curves were plotted，and associations between ADH1A expression and clinicopathological features were analyzed. Gene Ontology (GO) biological process enrichment analysis was performed to identify pathways enriched among proteins positively or negatively correlated with ADH1A expression and to evaluate their abundance differences between high and low ADH1A expression groups. Immune infiltration was analyzed using the CIBERSORT algorithm to assess differences in immune cell subsets between groups. Spatial transcriptomics data were analyzed to explore the spatial expression pattern of ADH1A. Finally，Western blot and immunohistochemistry (IHC) were performed on clinical HCC tissue samples to examine ADH1A expression and its relationship with MVI status. RESULTS：ADH1A expression was significantly lower in tumor tissues compared to adjacent non-tumor tissues (P<0.01). Its expression was significantly associated with MVI (P<0.05)，and low ADH1A expression was strongly correlated with poor prognosis. GO enrichment analysis revealed that proteins positively correlated with ADH1A were mainly involved in metabolic processes such as organic acid metabolism，while negatively correlated proteins were enriched in cell-matrix adhesion and cell spreading pathways. Notably，seven key adhesion-related proteins within the “cell adhesion” biological process were significantly upregulated in the low ADH1A expression group (all P<0.05). Immune infiltration analysis showed that na-ve CD4 T cells and resting mast cells were significantly decreased in the low ADH1A group (both P<0.05). Spatial transcriptomics，Western blot，and IHC consistently demonstrated reduced ADH1A expression in tumor regions compared to non-tumor regions，and lower expression in MVI-positive samples than in MVI-negative ones. CONCLUSION：ADH1A was downregulated in hepatocellular carcinoma and was significantly associated with microvascular invasion and poor prognosis. ADH1A may exert anti-tumor effects by modulating cell adhesion pathways and the immune microenvironment，suggesting its potential as a prognostic biomarker and therapeutic target.

OBJECTIVE：To investigate associations between urinary trace elements and osteoporosis risk in postmenopausal women in Shenzhen. METHODS：Based on a cross-sectional study，3 667 postmenopausal women were selected from the Shenzhen Aging-Related Diseases Cohort as participants. Demographic characteristics were collected via standardized questionnaires，and calcaneal bone mineral density (BMD) was assessed using quantitative ultrasound. Urinary concentrations of 20 trace elements were measured by inductively coupled plasma mass spectrometry (ICP-MS)，with all assays undergoing rigorous quality control. Multivariable logistic regression and quantile-based g-computation were employed to evaluate associations between urinary trace element levels and osteoporosis risk. RESULTS：Chromium (Cr)，copper (Cu)，zinc (Zn)，selenium (Se)，molybdenum (Mo)，vanadium (V)，lithium (Li)，titanium (Ti)，rubidium (Rb)，tin (Sn)，and barium (Ba) showed positive associations with osteoporosis risk (OR=1.41，2.33，1.35，1.36，1.34，1.62，1.07，2.39，1.42，1.48，and 1.56，respectively；all P<0.01). In contrast，cobalt (Co) and antimony (Sb) were negatively associated with osteoporosis risk (OR=0.80 and 0.81，respectively；P<0.01). Mixed-effect analysis revealed statistically significant joint effects of essential trace elements and potentially essential trace elements on osteoporosis risk (OR=1.15 and 1.13，respectively；P<0.01). CONCLUSION：This study found that different trace elements exerted distinct associations with osteoporosis risk in postmenopausal women，suggesting that imbalances in trace element metabolism may play a significant role in the pathogenesis of osteoporosis.

OBJECTIVE：To evaluate the impact of exercise training on primary yield and early biological quality of urine-derived stem cells (USCs) from a single volunteer and to determine feasibility of collecting samples at a fixed evening interval (20:00-21:00)，thereby providing guidance for non-invasive and standardized USCs isolation. METHODS：A self-controlled design was adopted. Urine samples were collected from the same volunteer at four time points-early morning (6:00-7:00)，forenoon (9:00-10:00)，afternoon (14:00-15:00) and evening (20:00-21:00)-to compare primary clone-forming efficiency and identify the optimal sampling period. Within this period，the volunteer first maintained normal daily activity for 7 days (rest group) and then performed a standardized run (2.8 km in 16-18 min) daily for another 7 days (exercise group)，with urine collected immediately post-exercise. USCs were isolated and cultured under identical protocols. Cellular morphology was assessed by morphological observation. Cell proliferation was assessed by MTT assay over 7 days to prepare growth curves. RT-qPCR was employed to measure mRNA levels of the pluripotency genes OCT4，C-MYC，SOX2 and NANOG，while Western blot was used to evaluate OCT4 and C-MYC protein expression. RESULTS：Evening collection (20:00-21:00) consistently yielded USC clones with the highest formation rate. Within this window，exercise-derived USCs displayed homogeneous morphology and lower senescence versus sedentary controls. The proliferation curve revealed a significantly higher D(570) on day 7 (P<0.01)，indicating sustained proliferative capacity. OCT4 and C-MYC mRNA levels were up-regulated (P<0.05 and P<0.01，respectively)，whereas SOX2 and NANOG mRNA levels remained unchanged (P>0.05). Consistently，OCT4 and C-MYC protein expression were markedly elevated (P<0.01). CONCLUSION：Evening urine collection (20:00-21:00) combined with exercise training significantly improved USC extraction efficiency and enhanced their early biological characteristics，offering a simple and feasible strategy for subsequent scalable expansion and clinical translation.

OBJECTIVE：To investigate expression of PTEN and PAX-2 in endometrial precancers，and their usefulness as immunohistochemical markers for diagnosis of atypical endometrial hyperplasia (AH). METHODS：Immunohistochemistry was performed to detect PTEN and PAX-2 expressions in 20 cases of AH，25 cases of suspicious atypical endometrial hyperplasia (suspicious AH) ，and 20 cases of endometrial hyperplasia without atypia (EH). RESULTS：When using 10% as the cutoff for weakened or absent PTEN protein expression in epithelial cells，the differences among the three groups were not statistically significant. However，when 75% was used as the cutoff，the differences in expression among the three groups became statistically significant (P<0.01). For PAX-2 protein，when using 10% as the cutoff for weakened or absent nuclear expression in epithelial cells，the difference between the atypical hyperplasia group and the non-atypical hyperplasia group was statistically significant (P=0.000). When 75% was used as the cutoff，the differences in expression among the three groups were statistically significant (P<0.01). Using 75% as the cutoff for weakened or absent expression in epithelial cells，50% of the samples in the atypical hyperplasia group showed overlapping loss of both PTEN and PAX-2 proteins. CONCLUSION：Extensive loss or reduction of PTEN protein expression (>75%) and loss or reduction of PAX-2 protein expression (>10%) may provide diagnostic value for endometrial atypical hyperplasia. The combined loss of both markers，when correlated with HE morphological features，demonstrated higher relevance for diagnosing endometrial atypical hyperplasia.

OBJECTIVE：To prepare 1,4-butanediol diglycidyl ether (BDDE) as a reference material for the detection of medical products. METHODS：Raw materials were screened and evaluated by gas chromatography-mass spectrometry，infrared spectroscopy，nuclear magnetic resonance spectroscopy and carbon spectroscopy. Its purity was checked by the mass balance method，and its content in organic components was checked by the gas chromatography area normalization method. The purity was also determined by the mass balance method，and the content by the gas chromatography 1% self-control method. Its uniformity and stability were investigated，and uncertainty was evaluated. In addition，the purity of BDDE was determined using three analytical instruments：gas chromatograph，gas chromatograph-mass spectrometer and liquid chromatograph-mass spectrometer；three solvents：acetone，water and ethyl acetate；and three quantitative methods：1% self-control method，area normalization method and external standard curve method. RESULTS：The purity of the acquired BDDE reference material was (98.14±0.21)%，and the accurate value of the fixed value was stable. The homogeneity was evaluated by one-way analysis of variance，F=1.137<F_0.05(14，30)，P>0.05，and it was considered that the standard substance to be tested was uniform within the 95% confidence interval. The short-term stability test results showed that it was stable at room temperature and at -18~-22 ℃ for 14 days，and the long-term stability was stable for 6 months. In addition，different instruments，solvents and methods had no significant effect on the measurement results，and the accuracy of the fixed value results of BDDE solution was verified. CONCLUSION：The acquired BDDE reference material showed accurate value，low uncertainty，good uniformity and stability，and can poteenteially be used for detection of medical products.

OBJECTIVE：To understand the acute toxicity and genotoxicity of Chionanthus retusus leaves. METHODS：Acute oral toxicity test was performed with a dose of 10 g/kg which was administered orally once and observe for two weeks. For the bacterial reverting mutation test，five doses were set up. spontaneous reverting，solvent control and positive control were set up. After inoculation，the cells were cultured at 37 ℃ for 48 hours，and the number of reverting colonies in each dish was counted. Both the mammalian red blood cell micronucleus test and the chromosome aberration test of mouse spermatocytes were set up with three dose groups of 1 250，2 500 and 5 000 mg/kg. At the same time，a solvent control group and a positive control group were set up. The test substance was administered by gavage. The mammalian red blood cell micronucleus test adopted the 30-hour test substance delivery method，and femoral bone marrow smears were collected. Incidence of micronuclei in polychromatic erythrocytes in the smear was determined. For the chromosome aberration test of mouse spermatocytes， test subjects were dosed continuously for 5 days. On the 13th day，bilateral testicular smears were taken to observe the types and corresponding quantities of chromosome aberrations in the smears. RESULTS：The oral LD₅₀ of Chionanthus retusus leaves on both male and female mice was greater than 10 g/kg，and it showed negative reactions in the bacterial reverse mutation test，mammalian red blood cell micronucleus test and mouse spermatocyte chromosomal aberration test. CONCLUSION：Under the conditions of this experiment，Chionanthus retusus leaves were non-toxic and did not show genotoxicity.