Immunosenescence is an inherent and crucial aspect of the aging process. Malignant tumors which often develop among senior individuals are associated with immunosenescence. Besides the immune system's intrinsic aging，cancerous cells can exacerbate immunosenescence. This combination can lead to a reduction of young immune cells and an increase of older immune cells. Consequently，the immune system would have reduced ability to combat tumors. Interrupting the reciprocal interaction between malignant tumors and immunosenescence，as well as reversing the effects of immunosenescence，can hold promise for enhancing antitumor responses and improving long-term survival of cancer patients.

OBJECTIVE：This study aimed to examine the impact of size-segregated and source-specific ambient particles on preeclampsia risk. METHODS：This study was conducted based on the antenatal examination records from Maternal and Child Health Hospital from 2014-2018 in Beijing，China. Particle number concentrations (PNC) of particles in size fractions of 5-560 nm and meteorological data in this study area were collected. The sources of PNC_5-560 were apportioned using the positive matrix factorization method. Logistic regression was used to analyze associations between maternal exposure to ambient particles and preeclampsia risk. RESULTS：Maternal exposure to particles in size fractions of 5-200 nm during preconception and early pregnancy was associated with increased risk of preeclampsia. Per an interquartile range (IQR) increment in PNC_25-100 and PNC_100-200 exposure during preconception，the excess risks of PE increased by 36%[OR(odd ratio)=1.36，95%CI(1.04，1.76)] and 40%[OR=1.40，95%CI(1.12，1.76)]，respectively. Per an IQR increment in PNC_5-25 and PNC_100-200 exposure during early pregnancy，the excess risks of PE increased by 46%[OR=1.46，95%CI(1.15，1.83)] and 40%[OR=1.40，95%CI(1.08，1.82)]，respectively. Maternal exposure to nucleation and gasoline vehicle emissions during preconception and early pregnancy was associated with the risk of preeclampsia. CONCLUSION：Maternal exposure to traffic-related ultrafine particles during preconception and early pregnancy may increase the risk of preeclampsia.

OBJECTIVE：To investigate the expression and regulation of the ribosomal protein S6 kinase β-1(S6K1) on the malignant phenotype of breast cancer cells. METHODS：Amplification and expression of S6K1 in breast cancer tissues were analyzed by cBioPortal and GEPIA databases，and their relationships with clinical characteristics of the breast cancers were also analyzed. Small interfering RNA was employed to knock down S6K1 in the breast cancer MCF7 cells in vitro to investigate its impact on protein expression profile using mass spectrometry，stemness of breast cancer cells using the sphere formation assay，and migration ability using the migration assay. RESULTS：S6K1 gene exhibited frequent amplification in breast cancer tissues，with a higher amplification rate in invasive compared with non-invasive breast cancers (P<0.05)，and with significant relationship to poor prognosis of patients (P<0.01). In addition，the expression was higher in breast cancer tissues compared with adjacent tissues (P<0.01)，while the expression levels did not differ significantly among different stages of breast cancer (P>0.05). Mass spectrometry revealed 251 upregulated and 224 downregulated proteins following the S6K1 knockdown in the MCF7 cells. GO pathway enrichment analysis indicated that S6K1 regulated the expression of multiple proteins involved in biological processes such as cytoplasmic translation，protein stabilization，stem cell population maintenance，and cell migration. Additional assays demonstrated that S6K1 knockdown significantly inhibited the stemness phenotype and migration ability of breast cancer cells (P<0.05). CONCLUSION：S6K1 regulated the expression of proteins involved in multiple biological processes in breast cancer cells in vivo，and the knockdown of S6K1 significantly inhibited the stemness and migration ability of breast cancer cells in vitro，indicating a crucial regulatory role for S6K1 and highlighting its potential as a novel therapeutic target for breast cancer therapy.

OBJECTIVE：To investigate expression of the major facilitator superfamily domain-containing protein 2a (MFSD2A) in hepatocellular carcinoma (HCC) tissues，and its correlation with clinical characteristics and prognosis of HCC patients. METHODS：The transcriptome data from 424 cases of HCC and 50 adjacent non-cancerous tissues，along with relevant clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Using a bioinformatics platform，expression of MFSD2A across various cancer types were compared. Association between MFSD2A expression and prognosis in HCC patients were evaluated using the Kaplan-Meier Plotter database. Additionally，a protein-protein interaction network of MFSD2A was constructed using the STRING database，related genes were retrieved using the GEPIA2 database，and pathway enrichment was analyzed to explore the molecular function of MFSD2A. Immunohistochemistry was performed to validate the expression of MFSD2A protein in HCC tumor tissues. RESULTS：Analysis of the TCGA data revealed significant differences in MFSD2A gene expression levels across various tissues. Specifically，MFSD2A was significantly under expressed in HCC tissues compared to adjacent tissues (P<0.01). Moreover，the expression increased in the over 60 age group (P=0.014)，in the G1 pathological grade group (P<0.01)，and in the group with AFP blood levels ≤400 ng/mL (P<0.01). High expression of MFSD2A was associated with significantly prolonged overall survival (P=0.008)，progression-free survival (P=0.008)，and recurrence-free survival (P=0.016) in patients. MFSD2A and its interacting proteins primarily participated in lipid metabolism-related PPAR signaling pathways. Immunohistochemistry analyses indicated that patients with high MFSD2A expression had better prognosis (P=0.016) compared to those with low expression，and serum AFP levels decreased with increasing MFSD2A scores. CONCLUSION：Low expression of MFSD2A was observed in HCC tissues and was associated with poor prognosis in patients. The results indicate that MFSD2A inhibited the progression of HCC by regulating hepatic lipid metabolism，and suggest that it may be a therapeutic target for hepatocellular carcinoma.

OBJECTIVE：Due to the high invasiveness and mortality of glioma，it is necessary to identify prognostic markers，such as glioma-associated hub genes，for improved treatment of this cancer. METHODS：Based on the Gene Expression Omnibus (GEO) database and limma R package，differentially expressed genes of glioma were downloaded，and oxidative stress-related genes based on the Genecard database. GSE31095 dataset (population from Netherlands and Sweden) was downloaded from the GEO database. Based on the GSE31095 dataset and limma R package，differentially expressed genes of glioma were identified. Hub genes were investigated using the protein-protein interaction (PPI)，the Gene Ontology (GO)，and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The Cancer Genome Atlas (TCGA) databases (population from the USA) and Chinese Glioma Genome Atlas (CGGA) databases (population from China) were used to verify the hub genes. Subsequently，random forest analysis，Kaplan-Meier analysis，and Cox proportional hazard analysis were conducted on the hub genes using the clinical data from the CGGA databases (mRNAseq_325). These analyses aimed to elucidate the diagnostic and prognostic significance of the identified hub genes. RESULTS：214 differentially expressed genes were identified，of which 205 were up-regulated and 9 were down-regulated. GO function enrichment analysis yielded 3 entries，including biosynthetic processes，translation processes，and ribosomes. The KEGG pathway enrichment analysis yielded 2 signaling pathways which were mainly involved in the immune system and antigen presentation. Ten hub genes were selected，and they were consistent with the results verified by the TCGA and CGGA cohorts. Four key genes，RPL7，RPL8，RPS3A，and RPS7，were identified with the overlap results from random forest algorithm，KM，and ggrisk analyses. The area under the ROC curve for the risk model for prognosis of gliomas was 0.691 at 1 year，0.687 at 3 years，and 0.685 at 5 years. CONCLUSION：Utilizing bioinformatics methods，the identification of hub genes in gliomas showed a novel avenue that could serve as a reference point for both clinical prognostic assessment and the development of new therapeutic strategies.

OBJECTIVE：To investigate effect and underlying mechanism of HSP90α inhibitor KW-2478 on malignant phenotypes of colorectal cancer (CRC) cells. METHODS：Using DMSO as solvent control，colorectal cancer cells RKO and DLD1 were treated with different concentrations of KW-2478. The proliferation rate of colorectal cancer cells was detected by CCK8 kit；the colony formation rate was detected by plate colony formation assay；flow cytometry was used to analyze the cell cycle；Western blot was used to detect the expression level and phosphorylation level of proliferation and cycle regulation-related proteins. RESULTS：Compared with the control group，the proliferation capacity of RKO cells treated with 0.8 μmol/L KW-2478 and DLD1 cells treated with 40 μmol/L KW-2478 decreased by more than 50%，and the IC₅₀ of both cells were (0.5±1.2) μmol/L and (40.0±3.1) μmol/L，respectively. After treatment with KW-2478，the sum colony formation rate of both cells were reduced by more than 40% when compared with the control group (P<0.01) . Meanwhile，KW-2478 significantly induced G2/M phase arrest (P<0.01). Upon KW-2478 treatment，the protein abundance of HSP90a client proteins EGFR，AKT and S6，and the phosphorylation levels of AKT，ERK and S6 were reduced，while the expressions of mitosis-specific marker p-Histone H3 and Cyclin B1 protein were upregulated. CONCLUSION：KW-2478 significantly inhibited the proliferation viability and colony formation ability of RKO and DLD1 and induced markedly G2/M phase arrest. The observed effects may be related to inhibiting the activity of EGFR-related signaling pathways and upregulating the expression of cycle-related proteins.

OBJECTIVE：To investigate correlations between purinergic receptor X1 (P2RX1) and different clinical pathological factors and tumor infiltration parameters in patients with ovarian serous carcinoma (OV)，and to provide new clues for OV immunotherapy. METHODS：Serum samples and tissues were collected from OV patients. Healthy adults and non-cancer patients were used as controls. Immunohistochemistry (IHC)，reverse transcriptation fluorescence quantitative PCR (RT-qPCR)，enzyme-linked immunosorbent assay (ELISA) and bioinformatics methods were used to determine expression patterns of P2RX1 in samples from patients. The TCGA database was used to analyze correlations between expression levels of P2RX1 and different clinicopathological indicators in the patients；to screen differential gene expressions，to identify signaling pathways and biological functions of P2RX1；and to analyze correlations between P2RX1 and immune cell infiltration abundance and tumor immunity. RESULTS：The IHC results show that P2RX1 was mainly expressed in normal ovarian epithelium；the RT-qPCR results show that expression of P2RX1 mRNA was lower in OV than in non-cancer tissues (P<0.05)；the ELISA results show that the expression of P2RX1 protein in the serum of the patients was lower than that of normal healthy adults (P<0.05). Results from analysis of the TCGA database show that patients with higher expression of P2RX1 had longer survival rates and better prognosis (P<0.05) than those with lower expressions. P2RX1 was associated with tumor purity and age of the patients (P<0.05). Results from the enrichment analysis show that the differentially expressed genes of P2RX1 were mainly enriched in biological processes such as immune cell differentiation and development. P2RX1 was found to be associated with multiple immune checkpoints in OV，such as TGFB1，SLAMF7，and CD27. P2RX1 was significantly and positively correlated with B cell marker genes such as CD79A，CD79B，and CD19 in OV (r>0.4，P<0.05). CONCLUSION：Low expression of P2RX1 in OV was associated with poor prognosis in patients. P2RX1 might be involved in processes such as immune cell infiltration and differentiation in the microenvironment of OV patients.

OBJECTIVE：To develop a rat model for investigating effects of acute ozone exposure on lung tissue injury in rats. METHODS：48 SPF-grade SD rats ，half male and half female，were randomly divided into 4 groups：control，and 1.0，2.0 and 4.0 ppm exposures. The environmental exposure was for 4 h every day for 7 d. After exposure，lung tissues and blood were collected，and changes of lung coefficient were calculated. Oxidative stress indexes of malondialdehyde (MDA)，superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissue homogenate were measured. Changes of serum inflammatory factors (IL-1β and TNF-α) and pathological status of lung tissues were detected. RESULTS：Compared with the control group，the lung coefficient of rats increased gradually under different concentrations of ozone exposure (P<0.05). In addition，MDA content in lung tissues increased with increased concentrations (P<0.01). SOD content in lung tissue of female rats was increased (P<0.01)，and SOD content in lung tissue of male rats was first increased and then decreased (P<0.05). The content of GSH-Px was increased (P<0.01). The serum levels of TNF-α in female rats were increased (P<0.05)，and the levels of IL-1β and TNF-α in male rats were increased (P<0.05). Histopathological results showed that the alveolar septum of lung tissues in female rats was thickened and there was inflammatory cell infiltration. Thickening of the alveolar septum of the 2.0 and 4.0 ppm groups was worse than that of the control group. In the control group，the pulmonary alveolar septum was slightly thickened and there was mild inflammation. The thickening of alveolar interval in each ozone dose group was more severe than that in the control group，and large-scale lung tissue consolidation was observed in the 2.0 and 4.0 ppm dose groups. CONCLUSION：Ozone exposure caused pathological injury，oxidative stress and inflammation in rat lung tissues，and the toxic effects showed sex gender differences.

OBJECTIVE：Genomics was used to explore the structure and functional expression of gut microbiota in rats under high temperature and humidity environments，as well as their correlation with serum brain-gut peptide indicators. METHODS：Sixteen adult male SD rats were randomly divided into two groups：the normal temperature and humidity group and the high temperature and humidity group. The normal temperature and humidity group were placed in a constant temperature and humidity box with a temperature of (25±2) ℃ and a humidity of (50±5)%，while the high temperature and humidity group with a temperature of (40±2) ℃ and a humidity of (70±5)% for 7 days. During this period，the rats were fed and watered normally. The fecal samples of the two groups were collected in a 1.5 mL centrifuge tube，and serum samples were collected through the abdominal aorta. 16S rDNA and metagenomic sequencing methods were used to analyze fecal samples of rats in the two groups. Changes in bacterial community structure and function under high temperature and humidity environments were identified. Enzyme linked immunosorbent assay (ELISA) was used to measure serum cholecystokinin (CCK) levels in rats. Spearman correlation analysis was applied to investigate the correlation between differential microbiota and brain gut peptides. RESULTS：Animal behavioral observations indicated that rats in the high temperature and humidity group were restless，with their front paws scratching their faces and poor mental state over time，and their activity was gradually decreased. The 16S rDNA and metagenomic sequencing results showed that the high temperature and humidity environment significantly reduced the alpha and beta diversity of the intestinal microbiota compared with the normal temperature and humidity group，leading to an increase in the ratio of Firmicutes to Bacteroidetes. The core differential microbiota was obtained through species difference analysis，the up-regulated microbiota were Corynebacterium and Streptomyces，and the down-regulated microbiota were Prevotella，Corynebacterium，Helicobacter pilosum，and Ruminococcus. Functional analysis results indicated that high temperature and humidity mainly affect metabolic processes such as arginine and proline metabolism，porphyrin metabolism，retinol metabolism，and biosynthesis，as well as glycolysis/glycogenesis，ABC transporters，ribosomes，etc. The ELISA test results showed that the serum CCK content of SD rats in the high-temperature and high humidity group was significantly reduced. CONCLUSION：High temperature and humidity environments caused abnormalities in the structure and function of microbial communities significantly，which in turn affected the changes in CCK levels through core differential microbial communities，thereby affecting emotional regulation. Functional enrichment analysis showed that there was a correlation between gut microbiota and emotional changes in high temperature and humidity environments，which in turn had an important relationship with neurological diseases. This study enriches the understanding of the impact of the environment on gut microbiota and provides support for clinical diagnosis and research.