Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Background and Aims:Gastric cancer is a common and highly lethal malignancy of the digestive system.The efficacy of current treatment strategies remains limited,highlighting the urgent need to identify novel therapeutic targets.This study employed a Mendelian randomization(MR)approach to integrate GWAS data with pQTL data,aiming to systematically identify and validate plasma proteins that are causally associated with gastric cancer,thereby providing a theoretical basis for targeted therapy.Methods:A two-sample Mendelian randomization analysis was conducted using GWAS data on gastric cancer and plasma pQTL datasets to infer causal relationships.External independent datasets were used for validation.Multi-dimensional sensitivity analyses-including reverse causality testing,Bayesian colocalization,and phenome-wide scans-were performed to ensure the robustness of the findings.Protein-protein interaction networks were constructed via the STRING database to elucidate the biological pathways of candidate proteins,and the DrugBank database was utilized to predict potential therapeutic agents.Results:A total of 16 plasma proteins were initially identified as causally associated with the risk of gastric cancer.After external validation and sensitivity analyses,ICAM2,IGF1R,LIFR,and MET were confirmed as key candidate targets.Drug database analysis indicated that dalotuzumab(targeting IGF1R)and efalizumab(potentially modulating the ICAM2 pathway)may have therapeutic potential.Conclusion:Through a multi-omics Mendelian randomization framework,this study systematically identified four plasma proteins-ICAM2,IGF1R,LIFR,and MET-that exhibit stable causal associations with gastric cancer.These targets offer novel insights into the molecular pathogenesis of gastric cancer and provide a theoretical foundation for developing targeted drugs and personalized treatment strategies.

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment of "biaoben acupoint combination" on cardiomyocyte mitochondrial fission in the rats with myocardial ischemia-reperfusion injury (MIRI) and explore its mechanism. METHODS: Fifty male SD rats were randomly divided into a sham-operation group, a model group, an EA pretreatment group, an EA pretreatment + Compound C group and an EA pretreatment+ML385 group, 10 rats in each group. In the EA pretreatment, the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, EA was delivered at bilateral "Neiguan" (PC6), "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, with continuous wave and 2 Hz of frequency, 1 mA of current, once daily for consecutive 7 days. On day 8, in the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, 30 min before model preparation, the intraperitoneal injection with Compound C (0.3 mg/kg) and ML385 (30 mg/kg) was administered respectively. Except in the sham-operation group, the ligation of the left anterior descending coronary artery was performed to prepare MIRI rat model in the rest groups. In the sham-operation group, the thread was not ligated. After modeling, the content of reactive oxygen species (ROS) in the ischemic area was measured by flow cytometry, superoxide dismutase (SOD) was detected using xanthine oxidase method, and malondialdelyde (MDA) was detected using thiobarbituric acid (TBA) chromatometry. The morphology of myocardial tissue in the ischemic area was observed with HE staining, and the mitochondria ultrastructure of cardiomyocytes observed under transmission electron microscopy. Using immunofluorescence analysis, the positive expression of mitochondrial fission factor (MFF), mitochondrial fission 1 protein antibody (Fis1) and dynamin-related protein 1 (Drp1) was detected; and with immunohistochemical method used, the protein expression of adenosine monophosphate-activated protein kinase (AMPK), nuclear factor E2-associated factor2 (Nrf2) and Drp1 in the ischemic area was detected. RESULTS: Compared with the sham-operation group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 increased in the model group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 decreased (P<0.01), and the protein expression of Drp1 elevated (P<0.01). Compared with the model group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01), and the protein expression of Drp1 declined (P<0.01); and in the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the positive expression of MFF, Fis1 and Drp1, and the protein expression of Drp1 were all reduced (P<0.01). When compared with the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01, P<0.05), and the protein expression of Drp1 decreased (P<0.05). In comparison with the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the cardiac muscle fiber rupture, cell swelling and mitochondrial disorders were obviously alleviated in the EA pretreatment group. The morphological changes were similar among the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group. CONCLUSION Electroacupuncture pretreatment of "biaoben acupoint combination" attenuates myocardial injury in MIRI rats, probably through promoting the phosphorylation of AMPK and Nrf2, inhibiting the excessive mitochondrial fission induced by Drp1, and reducing mitochondrial dysfunction caused by mitochondrial fragmentation and vacuolation.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Myocardial Reperfusion Injury/physiopathology* ; Myocytes, Cardiac/cytology* ; Rats ; Acupuncture Points ; Mitochondrial Dynamics ; Humans ; Reactive Oxygen Species/metabolism* ; NF-E2-Related Factor 2/genetics* ; Superoxide Dismutase/metabolism*

Background and Aims:Gastric cancer is a common and highly lethal malignancy of the digestive system.The efficacy of current treatment strategies remains limited,highlighting the urgent need to identify novel therapeutic targets.This study employed a Mendelian randomization(MR)approach to integrate GWAS data with pQTL data,aiming to systematically identify and validate plasma proteins that are causally associated with gastric cancer,thereby providing a theoretical basis for targeted therapy.Methods:A two-sample Mendelian randomization analysis was conducted using GWAS data on gastric cancer and plasma pQTL datasets to infer causal relationships.External independent datasets were used for validation.Multi-dimensional sensitivity analyses-including reverse causality testing,Bayesian colocalization,and phenome-wide scans-were performed to ensure the robustness of the findings.Protein-protein interaction networks were constructed via the STRING database to elucidate the biological pathways of candidate proteins,and the DrugBank database was utilized to predict potential therapeutic agents.Results:A total of 16 plasma proteins were initially identified as causally associated with the risk of gastric cancer.After external validation and sensitivity analyses,ICAM2,IGF1R,LIFR,and MET were confirmed as key candidate targets.Drug database analysis indicated that dalotuzumab(targeting IGF1R)and efalizumab(potentially modulating the ICAM2 pathway)may have therapeutic potential.Conclusion:Through a multi-omics Mendelian randomization framework,this study systematically identified four plasma proteins-ICAM2,IGF1R,LIFR,and MET-that exhibit stable causal associations with gastric cancer.These targets offer novel insights into the molecular pathogenesis of gastric cancer and provide a theoretical foundation for developing targeted drugs and personalized treatment strategies.

Objective: To establish a method for the determination of 1-methoxy-2-propanol in urine using headspace solid phase micro-extraction coupled with gas chromatography. Methods: The 1-methoxy-2-propanol was enriched by headspace solid phase micro-extraction fiber coated with carbene/polydimethylsiloxane (CAR/PDMS) . Single factor rotation method was used to optimize the conditions of extraction temperature, salt amount, and extraction time. The separation was performed on DB-5 (30 m×0.32 mm×0.25 μm) capillary column and detected with flame ionization detector. The quantification was based on the standard curve. Results: The concentration of 1-methoxy-2-propanol in urine was linear in the range of 0.50-10.0 mg/L, and the linear correlation coefficient was 0.9993. The detection limit of the method was 0.14 mg/L, and the limit of quantification was 0.45 mg/L. The recovery was 85.8% to 104.7%, and the RSD of intra- and inter-batch precision were 3.25%-6.65% and 0.81%-3.96%, respectively. Conclusion The method is high sensitivity and simple operation, and is suitable for the determination of 1-methoxy-2-propanol in urine of occupational exposure population.

Objective To explore the effects of atmospheric haze and air pollutants(PM10, PM2.5), SO2, NO2 on hospital visits for cardiovascular diseases. Methods The relationship among atmospheric haze, air pollution and the outpatients data of Guangzhou for cardiovascular disease had been investigated by collecting the air pollution data, the meteorological data and cardiovascular diseases’ outpatients data in Guangzhou city from January 1, 2006 to December 31,2008 . The time-series analysis by auto-regression model was used, controlling for long -term trends, seasonal patterns and meteorological variables. Results Auto-regression model showed that the number of outpatients in 2008 was higher than that in 2006.The number was larger in April and December compared with that in January, and it was higher on Monday, Tuesday, Wednesday, Thursday and Friday than on Saturday, Sunday. There was a positive correlation between the haze level and cardiovascular outpatients. The number of hospital outpatients increased by 2.12 units with each additional day of the atmospheric haze. The haze level (lag2) of the former second day had a negative impact on the intraday data of outpatients. The residual parts showed that outpatients’ residual data (AR1, AR3) of the former first and third day had a positive effect on intraday outpatients’ residual data (increased by 52.25%, 26.1%), while the outpatients’ residual data of the former second day (AR2) had a negative effect on outpatients’ residual data of the present day (decreased by 17%). In addition, a variety of air pollutants (PM10, PM2.5, SO2, and NO2) showed some positive correlation, and had hysteresis. Conclusion The atmospheric haze, generated from suspended particulate, meteorological factor and gaseous pollutants, is the environmental pathogenic factor for the cardiovascular diseases, while the effects of single air pollutant on the hospital visit for cardiovascular diseases can be weakened by the haze pollution.