The virulence factor OipA in Asian isolates of Helicobacter pylori

Persistent infection by Helicobacter pylori, a gram-negative bacterium, is associated with gastric cancer. The outer membrane protein of H. pylori OipA has been identified as a virulence factor that induces inflammation and facilitates adhesion to epithelial cells by some studies. Our lab has determined that two of our collections of eight Asian strains of H. pylori possess a second copy of oipA, a condition that is not found among European, African or other western strains of H. pylori. The potential significance of this observation arises from the fact that the prevalence of gastric cancer is much higher in Asia than that of the west. We hypothesized that the frequent merodiploid nature (two gene copies in an otherwise haploid genome) of oipA among Asian H. pylori strains may lead to increased induction of the pro-inflammatory cytokine IL-8 and translocation of the effector protein CagA into epithelial cells. Such increase in virulence of Asian H. pylori strains may partially explain the high prevalence of gastric cancer in Asia. However, our results indicate that knocking out each oipA allele individually or ablating both alleles in a single mutant has no effect on IL-8 secretion by AGS cells, adherence ability to AGS cells and CagA translocation of H. pylori strain 98-46. However, our results of the mRNA levels of oipA in our mutant collection indicate transcript levels vary among the mutants

Research on the coordinated development of resource-based cities in Sichuan Province: from the perspective of industrial structure and ecological environment

During their journey of developing, resource-based cities gradually deplete the resources on which they rely for survival. Scientific and reasonable research on the industrial and ecological aspects of resource-based cities is conducive to the coordinated development of cities. In order to further analyze the industrial structure of resource-based cities systematically and analyze the comprehensive level of resource-based cities from multi-dimensional perspective. This paper took 8 resource-based cities in Sichuan Province as the research object, and constructed the index system from two systems: industrial structure and ecological environment, then the shift-share analysis, entropy weight method and capacity coupling coefficient model were used to analyze their level of industrial structure, ecological environment and the coupling relationship respectively. According to the results of the study, it can be concluded that the main influencing factor in the development of industrial structure is the industrialmix effect, while the ecological level presents a decreasing level due to the lack of control of total industrial solid waste and energy consumption. The coupling degree between industrial structure and ecological environment in resource-based cities in Sichuan Province is relatively stable, and the coupling coordination degree also gradually tends to a stable state. In the subsequent development, the focus should be on the coal mining and dressing industry and the power, heat production and supply industry. Starting with the actual industrial structure of resource-based cities and specific indicators that affected the ecological environment, this paper hereby analyzed the development momentum and unified and coordinated development status of resource-based cities. The main purpose of this paper is providing some technical support for resource-based cities to improve their coordinated urban development, and giving policy suggestions for the coordinated development of resource-based cities

Higher risk of cardiovascular mortality than cancer mortality among long-term cancer survivors

BackgroundPrevious studies focused more on the short-term risk of cardiovascular (CV) death due to traumatic psychological stress after a cancer diagnosis and the acute cardiotoxicity of anticancer treatments than on the long-term risk of CV death.MethodsTime trends in the proportions of CV death (PCV), cancer death (PCA), and other causes in deaths from all causes were used to show preliminary relationships among the three causes of death in 4,806,064 patients with cancer from the Surveillance, Epidemiology, and End Results (SEER) program. Competing mortality risk curves were used to investigate when the cumulative CV mortality rate (CMRCV) began to outweigh the cumulative cancer mortality rate (CMRCA) for patients with cancer who survived for more than 10 years. Multivariable competing risk models were further used to investigate the potential factors associated with CV death.ResultsFor patients with cancer at all sites, the PCV increased from 22.8% in the 5th year after diagnosis to 31.0% in the 10th year and 35.7% in the 20th year, while the PCA decreased from 57.7% in the 5th year after diagnosis to 41.2 and 29.9% in the 10th year and 20th year, respectively. The PCV outweighed the PCA (34.6% vs. 34.1%) since the 15th year for patients with cancer at all sites, as early as the 9th year for patients with colorectal cancer (37.5% vs. 33.2%) and as late as the 22nd year for patients with breast cancer (33.5% vs. 30.6%). The CMRCV outweighed the CMRCA since the 25th year from diagnosis. Multivariate competing risk models showed that an increased risk of CV death was independently associated with older age at diagnosis [hazard ratio and 95% confidence intervals [HR (95%CI)] of 43.39 (21.33, 88.28) for ≥ 80 vs. ≤ 30 years] and local metastasis [1.07 (1.04, 1.10)] and a decreased risk among women [0.82 (0.76, 0.88)], surgery [0.90 (0.87, 0.94)], and chemotherapy [0.85 (0.81, 0.90)] among patients with cancer who survived for more than 10 years. Further analyses of patients with cancer who survived for more than 20 years and sensitivity analyses by cancer at all sites showed similar results.ConclusionCV death gradually outweighs cancer death as survival time increases for most patients with cancer. Both the cardio-oncologist and cardio-oncology care should be involved to reduce CV deaths in long-term cancer survivors

Community-based lung cancer screening by low-dose computed tomography in China:First round results and a meta-analysis

OBJECTIVE: To evaluate the efficiency of low-dose computed tomography (LDCT) screening for lung cancer in China by analyzing the baseline results of a community-based screening study accompanied with a meta-analysis. METHODS: A first round of community-based lung cancer screening with LDCT was conducted in Tianjin, China, and a systematic literature search was performed to identify LDCT screening and registry-based clinical studies for lung cancer in China. Baseline results in the community-based screening study were described by participant risk level and the lung cancer detection rate was compared with the pooled rate among the screening studies. The percentage of patients per stage was compared between the community-based study and screening and clinical studies. RESULTS: In the community-based study, 5523 participants (43.6% men) underwent LDCT. The lung cancer detection rate was 0.5% (high-risk, 1.2%; low-risk, 0.4%), with stage I disease present in 70.0% (high-risk, 50.0%; low-risk, 83.3%), and the adenocarcinoma present in 84.4% (high-risk, 61.5%; low-risk, 100%). Among all screen-detected lung cancer, women accounted for 8.3% and 66.7% in the high- and low-risk group, respectively. In the screening studies from mainland China, the lung cancer detection rate 0.6% (95 %CI: 0.3%-0.9%) for high-risk populations. The proportions with carcinoma in situ and stage I disease in the screening and clinical studies were 76.4% (95 %CI: 66.3%-85.3%) and 15.2% (95 %CI: 11.8%-18.9%), respectively. CONCLUSIONS: The stage shift of lung cancer due to screening suggests a potential effectiveness of LDCT screening in China. Nearly 70% of screen-detected lung cancers in low-risk populations are identified in women

Preventing tumor progression to the bone by induced tumor-suppressing MSCs

Background: Advanced breast cancer metastasizes to many organs including bone, but few effective treatments are available. Here we report that induced tumor-suppressing (iTS) MSCs protected bone from metastases while un-induced MSCs did not. Methods: iTS MSCs were generated by overexpressing Lrp5, β-catenin, Snail, or Akt. Their tumor-suppressing capability was tested using a mouse model of mammary tumors and bone metastasis, human breast cancer tissues and cancer cell lines. Results: In a mouse model, the induced MSC-derived conditioned medium (MSC CM) reduced mammary tumors and suppressed tumor-induced osteolysis. Tumor-promoting genes such as CXCL2 and LIF, as well as PDL1, a blocker of T-cell-based immune responses were downregulated. Proteomics analysis revealed that heat shock protein 90 (Hsp90ab1), calreticulin (Calr) and peptidylprolyl isomerase B (Ppib), which are highly expressed intracellular proteins in many cancers, were enriched in MSC CM as atypical tumor suppressors. Thus, overexpressing selected genes that were otherwise tumorigenic rendered MSCs the tumor-suppressing capability through the atypical suppressors, as well as p53 and Trail. Notably, the inhibitory effect of Lrp5- and Akt-overexpressing MSC CMs, Hsp90ab1 and Calr presented selective inhibition to tumor cells than non-tumor cells. The development of bone-resorbing osteoclasts was also suppressed by MSC CMs. Conclusion: Collectively, the results showed an anti-tumor effect of iTS MSCs and suggested novel therapeutic approaches to suppress the progression of tumors into the bone

Identification of risk factors for infection after mitral valve surgery through machine learning approaches

BackgroundSelecting features related to postoperative infection following cardiac surgery was highly valuable for effective intervention. We used machine learning methods to identify critical perioperative infection-related variables after mitral valve surgery and construct a prediction model.MethodsParticipants comprised 1223 patients who underwent cardiac valvular surgery at eight large centers in China. The ninety-one demographic and perioperative parameters were collected. Random forest (RF) and least absolute shrinkage and selection operator (LASSO) techniques were used to identify postoperative infection-related variables; the Venn diagram determined overlapping variables. The following ML methods: random forest (RF), extreme gradient boosting (XGBoost), Support Vector Machine (SVM), Gradient Boosting Decision Tree (GBDT), AdaBoost, Naive Bayesian (NB), Logistic Regression (LogicR), Neural Networks (nnet) and artificial neural network (ANN) were developed to construct the models. We constructed receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) was calculated to evaluate model performance.ResultsWe identified 47 and 35 variables with RF and LASSO, respectively. Twenty-one overlapping variables were finally selected for model construction: age, weight, hospital stay, total red blood cell (RBC) and total fresh frozen plasma (FFP) transfusions, New York Heart Association (NYHA) class, preoperative creatinine, left ventricular ejection fraction (LVEF), RBC count, platelet (PLT) count, prothrombin time, intraoperative autologous blood, total output, total input, aortic cross-clamp (ACC) time, postoperative white blood cell (WBC) count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), PLT count, hemoglobin (Hb), and LVEF. The prediction models for infection after mitral valve surgery were established based on these variables, and they all showed excellent discrimination performance in the test set (AUC > 0.79).ConclusionsKey features selected by machine learning methods can accurately predict infection after mitral valve surgery, guiding physicians in taking appropriate preventive measures and diminishing the infection risk

SCUBA-2 Ultra Deep Imaging EAO Survey (STUDIES). II. Structural Properties and Near-infrared Morphologies of Faint Submillimeter Galaxies

We present structural parameters and morphological properties of faint 450 μm selected submillimeter galaxies (SMGs) from the JCMT Large Program, STUDIES, in the COSMOS-CANDELS region. Their properties are compared to an 850 μm selected and a matched star-forming samples. We investigate stellar structures of 169 faint 450 μm sources (S 450 = 2.8–29.6 mJy; S/N > 4) at z 2 mJy) and more extended than the star-forming galaxies in the same redshift range. For the stellar mass and SFR-matched sample at z sime 1 and z sime 2, the size differences are marginal between faint SMGs and the matched galaxies. Moreover, faint SMGs have similar Sérsic indices and projected axis ratios as star-forming galaxies with the same stellar mass and SFR. Both SMGs and the matched galaxies show high fractions (~70%) of disturbed features at z sime 2, and the fractions depend on the SFRs. These suggest that their star formation activity is related to galaxy merging and the stellar structures of SMGs are similar to those of star-forming galaxies. We show that the depths of submillimeter surveys are approaching the lower luminosity end of star-forming galaxies, allowing us to detect galaxies on the main sequence

Overexpression of Lrp5 enhanced the anti-breast cancer effects of osteocytes in bone

Osteocytes are the most abundant cells in bone, which is a frequent site of breast cancer metastasis. Here, we focused on Wnt signaling and evaluated tumor-osteocyte interactions. In animal experiments, mammary tumor cells were inoculated into the mammary fat pad and tibia. The role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse model. The results revealed that administration of osteocytes or their conditioned medium (CM) inhibited tumor progression and osteolysis. Osteocytes overexpressing Lrp5 or β-catenin displayed strikingly elevated tumor-suppressive activity, accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as p53. The antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating compound. Notably, silencing Lrp5 in tumors inhibited tumor progression, while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor progression. Osteocytes exhibited elevated Lrp5 expression in response to tumor cells, implying that osteocytes protect bone through canonical Wnt signaling. Thus, our results suggest that the Lrp5/β-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in osteocytes. We envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis