p­Phenylenediamine antioxidants in PM2.5: New markers for traffic in positive matrix factorization source apportionment.

The extensive utilization of rubber-related products can lead to a substantial release of p-phenylenediamine (PPD) antioxidants into the environment. In recent years, studies mainly focus on the pollution characteristics and health risks of PM2.5-bound PPDs. This study presents long-time scale data of PPDs and N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) in PM2.5 and proposes the innovative use of PPDs as new markers for vehicular emissions in the Positive Matrix Factorization (PMF) source apportionment. The results indicate that PPDs and 6PPD-Q were detectable in 100 % of the winter PM2.5 samples, and the concentration ranges of PPDs and 6PPD-Q are 15.6-2.92 × 103 pg·m-3 and 3.90-27.4 pg·m-3, respectively, in which 6PPD and DNPD are the main compounds. Moreover, a competitive formation mechanism between sulfate, nitrate, ammonium (SNA) and 6PPD-Q was observed. The source apportionment results show that the incorporation of PPDs in PMF reduced the contribution of traffic source to PM2.5 from 13.5 % to 9.5 %. In the traffic source factor profiles, the load of IPPD, CPPD, DPPD, DNPD and 6PPD reaches 91.8 %, 91.6 %, 92.9 %, 80.6 % and 87.2 %, respectively. It`s amazing that traditional markers of traffic source, which often overlap with coal burning and industrial sources, over-estimated the contribution of vehicles by one third or more. The discovery of PPDs as specific markers for vehicular emissions holds significant utility, particularly considering the growing proportion of new energy vehicles in the future. The results may prove more accurate policy implications for pollution control. SYNOPSIS: PPDs are excellent indicators of vehicle emissions, and PMF without PPDs over-estimated the contribution of traffic source to PM2.5.

SULF1 Activates the VEGFR2/PI3K/AKT Pathway to Promote the Development of Cervical Cancer.

BACKGROUND AND PURPOSE: Sulfatase 1 (SULF1) can regulate the binding of numerous signaling molecules by removing 6-O-sulfate from heparan sulfate proteoglycans (HSPGs) to affect numerous physiological and pathological processes. Our research aimed to investigate the effect of the SULF1-mediated VEGFR2/PI3K/AKT signaling pathway on tumorigenesis and development of cervical cancer (CC). METHODS: The expression and prognostic values of SULF1 in patients with CC were analyzed through bioinformatics analysis, RT-PCR, immunohistochemistry, and western blot assays. The function and regulatory mechanism of SULF1 in proliferation, migration, and invasion of cervical cancer cells were examined through lentivirus transduction, CCK8, flow cytometry analysis, plate colony formation assay, scratch assay, transwell assay, western blot, VEGFR2 inhibitor (Ki8751), and mouse models. RESULTS: SULF1 expression was significantly upregulated in CC tissues, which was significantly associated with poor prognosis of patients with CC. In vitro, the upregulation of SULF1 expression in cervical cancer HeLa cells promoted cell proliferation, colony formation, migration, and invasion while inhibiting apoptosis. Conversely, the downregulation of SULF1 expression had the opposite effect. In vivo, the upregulation of SULF1 expression resulted in a significant increase in both tumor growth and angiogenesis, while its downregulation had the opposite effect. Furthermore, western blot detection and cell function rescue assay confirmed that the upregulation of SULF1 in HeLa cells promoted the tumorigenic behaviors of cancer cells by activating the VEGFR2/PI3K/AKT signaling pathway. CONCLUSION: SULF1 plays an oncogenic role in the tumorigenesis and development of CC, indicating its potential as a novel molecular target for gene-targeted therapy in patients with CC.

Deep learning-assisted development and validation of an algorithm for predicting the growth of persistent pure ground-glass nodules.

Background: The prediction of the persistent pure ground-glass nodule (pGGN) growth is challenging and limited by subjective assessment and variation across radiologists. A chest computed tomography (CT) image-based deep learning classification model (DLCM) may provide a more accurate growth prediction. Methods: This retrospective study enrolled consecutive patients with pGGNs from January 2010 to December 2020 from two independent medical institutions. Four DLCM algorithms were built to predict the growth of pGGNs, which were extracted from the nodule areas of chest CT images annotated by two radiologists. All nodules were assigned to either the study, the inner validation, or the external validation cohort. Accuracy, sensitivity, specificity, receiver operating characteristic (ROC) curves, and areas under the ROC curve (AUROCs) were analyzed to evaluate our models. Results: A total of 286 patients were included, with 419 pGGN. In total, 197 (68.9%) of the patients were female and the average age was 59.5±12.0 years. The number of pGGN assigned to the study, the inner validation, and the external validation cohort were 193, 130, and 96, respectively. The follow-up time of stable pGGNs for the primary and external validation cohorts were 3.66 (range, 2.01-10.08) and 4.63 (range, 2.00-9.91) years, respectively. Growth of the pGGN occurred in 166 nodules [83 (43%), 39 (30%), and 44 (45%) in the study, inner and external validation cohorts respectively]. The best-performing DLCM algorithm was DenseNet_DR, which achieved AUROCs of 0.79 [95% confidence interval (CI): 0.70, 0.86] in predicting pGGN growth in the inner validation cohort and 0.70 (95% CI: 0.60, 0.79) in the external validation cohort. Conclusions: DLCM algorithms that use chest CT images can help predict the growth of pGGNs.

Loss of RBPMS in ovarian cancer compromises the efficacy of EGFR inhibitor gefitinib through activating HER2/AKT/mTOR/P70S6K signaling.

RBPMS may be a tumor suppressor in cancer, but its impact in modulation of drug sensitivity is unclear. This study aimed to investigate the regulatory role of RBPMS in cellular response to EGFR inhibitor gefitinib in ovarian cancer (OC). By western blotting assay, we revealed RBPMS was down-regulated in epithelial ovarian cancer tissues compared to normal control ovarian epithelial tissues. Overexpression of RBPMS inhibited cell viability and proliferation, and conferred gefitinib sensitivity, accompanied by reduced expression of p-EGFR, and vice versa. Proteomic analysis and flow cytometry experiments showed that RBPMS induced S-stage cell cycle arrest in gefitinib-treated OC cells. Co-IP assay suggested that HER2 was a downstream target of RBPMS, and RBPMS negatively regulated HER2 expression. HER2 counteracted the stimulation of RBPMS to cell growth blocking, gefitinib sensitivity and cell cycle arrest. We further demonstrated that RBPMS overexpression suppressed the activation of p-AKT, p-mTOR and p-P70S6K, which was rescued by up-regulation of HER2. The combination of AKT inhibitor MK2206 and gefitinib had a synergistic effect on OC cells with high level of RBPMS. In conclusion, through the direct inhibition of HER2/AKT/mTOR/P70S6K pathway, RBPMS may be a potential therapeutic target for improving gefitinib sensitivity in OC.

Phosphoproteomics reveals that cinobufotalin promotes intrahepatic cholangiocarcinoma cell apoptosis by activating the ATM/CHK2/p53 signaling pathway.

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor that originates from bile duct's epithelial cells and is usually characterized by insidious symptoms and poor prognosis. Cinobufotalin (CB), an active ingredient obtained from the Traditional Chinese Medicine ChanSu, is purported to exhibit a wide range of antitumorigenic activities. However, the mechanism by which it achieves such pharmacological effects remains elusive. Here, we disclosed the mechanism of action by which CB inhibits ICC cells. Initial experiments revealed that the proliferation of RBE and HCCC-9810 cells was significantly inhibited by CB with IC50 values of 0.342 µM and 0.421 µM respectively. CB induced the expression of caspase-3 subsequently leading to the apoptosis of ICC cells. Phosphoproteomics revealed that the phosphorylation of many proteins associated with DNA damage response increased. Kinase-substrate enrichment analysis revealed that ATM was activated after CB treatment, while CDK1 was inactivated. Activated ATM increased p-CHK2-T68 and p-p53-S15, which promoted the expression of FAS, DR4 and DR5 and triggered cell apoptosis. In summary, this work reveals the role of CB in inducing DNA damage and cell apoptosis involved in the activation of the ATM/CHK2/p53 signaling pathway, and indicates that CB may serve as a chemotherapeutic drug candidate for ICC treatment.

Endometrial stromal cells treated by tumor necrosis factor-α stimulate macrophages polarized toward M2 via interleukin-6 and monocyte chemoattractant protein-1.

AIM: This study aimed to investigate the effects of endometrial stromal cells (ESC)-derived interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 on macrophage polarization in endometriosis. METHODS: Macrophage polarization was measured in eutopic endometrium of control participants ('normal endometrium'), eutopic endometrium of patients with endometriosis ('eutopic endometrium') and ectopic endometrium of endometriosis patients ('ectopic endometrium') by immunohistochemical staining. Expression of IL-6 and MCP-1 were measured in the eutopic and ectopic endometrium through enzyme-linked immunosorbent assays. Expression of CD163 was measured in human acute monocytic leukemia (THP-1) cell-derived macrophages that were treated with conditional medium induced by tumor necrosis factor (TNF)-α, TNF-α + anti-IL-6 or TNF-α + anti-MCP-1 via flow cytometry. RESULTS: The ratio of CD163+/CD68+ macrophages in the normal endometrium was higher than that in the eutopic endometrium, while differences between the eutopic and ectopic endometrium were not statistically significant. IL-6 and MCP-1 exhibited enhanced expression in the ectopic endometrium group and decreased expression in the eutopic endometrium group. TNF-α could promote the expression of ESC-derived IL-6 and MCP-1. Intervention with TNF-α-induced conditioned medium resulted in the upregulation of CD163 in THP-1 cells, while conditional medium induced with IL-6 and MCP-1 neutralizing antibodies decreased the proportion of CD163+ macrophages significantly. CONCLUSION: In endometriosis patients, the macrophages of the eutopic endometrium polarize toward M1 compared with the normal endometrium, and those of the ectopic endometrium were mainly M2-polarized. Under the action of TNF-α, ESC-derived IL-6 and MCP-1 could stimulate peritoneal macrophages toward M2-polarization, which could modulate endometriosis.

Associations between intimate partner violence with emotion regulation and selfefficacy among young students with love experience / 中国学校卫生

Objective@#To understand the current situation of intimate partner violence (IPV) among young students in Chengdu and its relationship with emotion regulation self-efficacy,and to provide a reference for conducting the education on close relationship.@*Methods@#Totally 1 041 young students with love experience in Chengdu were selected by by stratified cluster random sampling to explore potentional factors related to IPV.@*Results@#The incidence of IPV perpetration among young students with love experience was as high as 69.6% and the incidence of IPV victimization was 62.2%. Young students had committed(65.4%) or been subjected(64.0%) to more than three intimate partner violence. 59.92% young students were both perpetrators and victims of IPV. Multiple Logistic regression analysis showed that compared with young female students, young male students were not prone to commit violence in intimate relationships(OR=0.59), but may become victims of IPV(OR=1.91). More than half a year in love(OR=1.70), cohabitation(OR=2.47), bullying by peers (OR=1.54) and interference by parents (OR=1.63) were risk factors for IPV perpetration. Among them, more than half a year in love (OR=1.51) and cohabitants (OR=2.52) were positively associated with IPV victimization. The efficacy of managing negative emotions was a negatively associated with IPV perpetration (OR=0.96) and victimization(OR=0.97)(P<0.05).@*Conclusion@#The phenomenon of intimate partner violence among young students is more common, which is closely related to the rearing style of young students, peer relationship, love relationship and the ability to manage negative emotions, which should be paid attention to.