Role of a Genetic Variant on the 15q25.1 Lung Cancer Susceptibility Locus in Smoking-Associated Nasopharyngeal Carcinoma

Background: The 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC). Methods: In this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and alcohol consumption. Univariate and multivariate logistic regression analyses were used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI)

DCLK1 Promotes Malignancy of A549 Cell Line by Activating FAK/PI3K/AKT/mTOR Pathway

ObjectiveTo investigate the effects of doublecortin-like kinase 1 (DCLK1) on the malignant biological behaviors, such as proliferation, migration, and invasion, of A549 cell line and their corresponding mechanisms. MethodsDCLK1-overexpressing A549 cell lines were established through lentiviral infection, and DCLK1 expression was validated by using RT-PCR and Western blot analysis. Proliferation ability was assessed with CCK-8 and plate cloning assays, and migration and invasion abilities were examined with Transwell assays. The pathway regulated by DCLK1 in lung adenocarcinoma was analyzed on the basis of the TCGA lung adenocarcinoma cohort with pathway enrichment analysis and verified through Western blot analysis. ResultsDCLK1 overexpression in A549 cells promoted cell proliferation, migration, and invasion. The inhibition of the FAK/PI3K/AKT/mTOR signaling pathway impaired the DCLK1-mediated malignant behavior of A549 cells. ConclusionDCLK1 promotes the malignant behavior of A549 cells through the activation of the FAK/PI3K/AKT/mTOR signaling pathway

Defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1–derived O-glycans

The core 1 β1-3-galactosyltransferase (T-synthase) transfers Gal from UDP-Gal to GalNAcα1-Ser/Thr (Tn antigen) to form the core 1 O-glycan Galβ1-3GalNAcα1-Ser/Thr (T antigen). The T antigen is a precursor for extended and branched O-glycans of largely unknown function. We found that wild-type mice expressed the NeuAcα2-3Galβ1-3GalNAcα1-Ser/Thr primarily in endothelial, hematopoietic, and epithelial cells during development. Gene-targeted mice lacking T-synthase instead expressed the nonsialylated Tn antigen in these cells and developed brain hemorrhage that was uniformly fatal by embryonic day 14. T-synthase–deficient brains formed a chaotic microvascular network with distorted capillary lumens and defective association of endothelial cells with pericytes and extracellular matrix. These data reveal an unexpected requirement for core 1–derived O-glycans during angiogenesis

Elijah: Eliminating Backdoors Injected in Diffusion Models via Distribution Shift

Diffusion models (DM) have become state-of-the-art generative models because of their capability to generate high-quality images from noises without adversarial training. However, they are vulnerable to backdoor attacks as reported by recent studies. When a data input (e.g., some Gaussian noise) is stamped with a trigger (e.g., a white patch), the backdoored model always generates the target image (e.g., an improper photo). However, effective defense strategies to mitigate backdoors from DMs are underexplored. To bridge this gap, we propose the first backdoor detection and removal framework for DMs. We evaluate our framework Elijah on hundreds of DMs of 3 types including DDPM, NCSN and LDM, with 13 samplers against 3 existing backdoor attacks. Extensive experiments show that our approach can have close to 100% detection accuracy and reduce the backdoor effects to close to zero without significantly sacrificing the model utility.Comment: AAAI 202

Tanshinone IIA Protects against Dextran Sulfate Sodium- (DSS-) Induced Colitis in Mice by Modulation of Neutrophil Infiltration and Activation

Neutrophils play a critical role in the initiation and maintenance of intestinal inflammation. However, conventional neutrophil-targeted therapies can impair normal host defense. Tanshinone IIA has been recently revealed to act directly on neutrophils. Hence, we aimed at investigating whether Tanshinone IIA can protect against experimental colitis through modulation of neutrophils. We induced colitis in C57BL/6 mice by giving 3% dextran sulfate sodium (DSS) orally, and meanwhile, we treated mice daily with Tanshinone IIA intraperitoneally. The severity of colitis was evaluated by calculating disease activity index (DAI) and histological parameters. Neutrophil infiltration and activation in the colons of mice were measured. Moreover, whether Tanshinone IIA has direct effects on neutrophil migration and activation was determined in vitro. Our data showed that Tanshinone IIA significantly ameliorated the severity of DSS-induced colitis in mice, evidenced by the reduced DAI and improved colonic inflammation. In addition, Tanshinone IIA decreased neutrophil infiltration of intestinal mucosa and activation and reduced colonic inflammatory cytokines in DSS-treated mice. Furthermore, Tanshinone IIA was demonstrated to significantly suppress neutrophil migration and activation. These results provide compelling evidence that Tanshinone IIA has a therapeutic potential for alleviating inflammatory colitis in mice, which is possibly mediated by the immunomodulation of neutrophils

The research on the immuno-modulatory defect of Mesenchymal Stem Cell from Chronic Myeloid Leukemia patients

Overwhelming evidence from leukemia research has shown that the clonal population of neoplastic cells exhibits marked heterogeneity with respect to proliferation and differentiation. There are rare stem cells within the leukemic population that possess extensive proliferation and self-renewal capacity not found in the majority of the leukemic cells. These leukemic stem cells are necessary and sufficient to maintain the leukemia. While the hematopoietic stem cell (HSC) origin of CML was first suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also being investigated. We have previously isolated fetal liver kinase-1-positive (Flk1+) cells carrying the BCR/ABL fusion gene from the bone marrow of Philadelphia chromosome-positive (Ph+) patients with hemangioblast property. Here, we showed that CML patient-derived Flk1+CD31-CD34-MSCs had normal morphology, phenotype and karyotype but appeared impaired in immuno-modulatory function. The capacity of patient Flk1+CD31-CD34- MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro. CML patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than HSCs. MSCs might be a potential target for developing efficacious cures for CML