Loureirin A is a narrow-spectrum antimicrobial agent against Helicobacter pylori.

Currently, Helicobacter pylori eradication by antibiotic therapy faces various challenges, including antibiotic resistance, side effects on intestinal commensal bacteria, and patient compliance. In this study, loureirin A (LrA), a traditional Chinese medicine monomer extracted from Sanguis Draconis flavones, was found to possess specific antibacterial activity against H. pylori without the bacteria displaying a tendency to develop resistance in vitro. LrA demonstrated a synergistic or additive effect when combined with omeprazole (a proton pump inhibitor) against H. pylori. The combination of LrA and omeprazole showed promising anti-H. pylori potential, exhibiting notable in vivo efficacy comparable to standard triple therapy in mouse models infected with both drug-sensitive and drug-resistant H. pylori strains. Moreover, the narrow-spectrum antibacterial profile of LrA is reflected in its minimal effect on the diversity and composition of the mouse gut microbiota. The underlying mechanism of action of LrA against H. pylori involves the generation of bactericidal levels of reactive oxygen species, resulting in apoptosis-like cell death. These findings indicate that LrA is a promising lead compound targeting H. pylori without harming the commensal bacteria.

An improved adaptive position tracking strategy for automatic shift actuator with uncertain parameters.

Realizing precise and fast position control of the gear is a challenging issue because of its nonlinearity, parameter uncertainty and external disturbance. Therefore, this paper researches the clutch position control considering the influence because of the factor on the system performance. By virtue of the traditional adaptive control method, an improved strategy based on finite time theory is proposed to further improve the convergence rate as well as the position tracking precision. First, a model of electromechanical clutch actuator system is established by theoretical analysis. Then, an enhanced adaptive controller is designed using finite time idea by introducing power function in the virtual control. And parameter update rate is adopted in the control action. Next, the stability of the control system is proved theoretically. Finally, Matlab simulations and experimental bench test are carried out to exhibit the effectiveness of the presented method. The results show that the satisfactory performance has been achieved with accurate position tracking and fast convergence speed.

Research on clutch position control based on backstepping method for small-sized tractors.

Tractors installed automated manual transmission can avoid discomfort for the drivers because of excessive limbs intervention as well as improve shift quality. Automatic clutch control is critical for the performance of the automated manual transmissions. For a good operation, precise and fast control of clutch position is mandatory. In order to meet these requirements, an enhanced strategy focused on the clutch is presented adopting a simple tracking control method based on the detailed models in this study. Clutch models including DC motor model and mechanical actuator model are established and transformed to a controllable model. On the basis of the control model, a clutch position tracking control scheme is proposed composed of motor control circuit and motor angle tracking controller designed according to the backstepping method. Simulations are carried out in comparation with the internal model control method, and the results demonstrate the effectiveness of the presented control scheme by superior rapidity and accuracy of the controller response for the clutch position tracking system.

Trajectory tracking for agricultural tractor based on improved fuzzy sliding mode control.

Trajectory tracking is one of the key technologies for tractor automatic navigation. Its main purpose is to adjust the steering mechanism of the tractor to follow the planned trajectory. Thus, in this paper a trajectory tracking control system is designed for an agricultural tractor with the electric power steering mechanism. A DC brush motor is added on the steering column of the tractor and the hardware circuits for the steering controller are designed to control the front wheel angel. The three degrees of freedom model of the tractor is established, and a trajectory tracking control system is proposed including a fuzzy sliding mode controller and a steering angle tracking controller designed according to the internal mode control and minimized sensitivity theory. The effectiveness of the designed trajectory tracking control system is demonstrated by simulation analyses in reference to the planed trajectory.

Warning and active steering rollover prevention control for agricultural wheeled tractor.

Tractor rollover is regarded as the most fatal incident in agricultural production, but some of which can be avoided by timely anti-rollover warning and active control. There have been a lot of researches on the tractor rollover model building and rollover protective structure designing but few on the anti-rollover control. The purpose of this study is to develop a cheaper and practical anti-rollover control system based on active steering technique and to prove the efficiency of the proposed scheme for the wheeled tractors. A three-degree-of-freedom rollover dynamics model including automatic steering system is established. A control scheme by adjusting the roll angle to keep the stability based on the adaptive sliding mode control is proposed with the estimated lateral velocity according to the feedback correction principle. Front wheel angle tracking controller is designed adopting internal model control (IMC) theory. Simulation results exhibit that the active anti-rollover control can calculate the stability index in real time and can keep it within the stable range by adjusting the front steering wheel angle. It is prospective for the proposed scheme to provide a valuable reference to reduce tractor rollover accidents.

Position Control of Gear Shift based on Sliding Mode Active Disturbance Rejection Control for Small-Sized Tractors.

A modified sliding mode active disturbance rejection control (MSMADRC) position system is designed for small-sized tractors to solve the longer shift time and reduced shifting quality because of the inaccurately motor control used for the automatic mechanical transmission (AMT) gear shift actuator. Firstly, the control model of the motor with total disturbance is established. Then an extended observer is presented to monitor the unmodeled dynamics and various disturbances of the system in real time, at the same time the extended state and the system feedback variables are constructed as the system variables of the sliding mode control (SMC) algorithm. Secondly, a sliding mode surface instead of the nonlinear control law in the active disturbance rejection control (ADRC) algorithm is designed, which realizes the fast and accurate tracking of the position. What's more, the stability of the control system is proved by Lyapunov theory. Lastly, the simulation results demonstrate that the position control precision by MSMADRC is higher 37% than by SMC and higher 75% than by ADRC. Furthermore, the response speed of MSMADRC is the fastest, it only takes about 0.7s.

Gastric cancer proliferation and invasion is reduced by macrocalyxin C via activation of the miR-212-3p/Sox6 Pathway.

Gastric cancer is a malignancy of very poor prognosis and survival rates. Macrocalyxin C is a Chinese herb-derived diterpenoid compound that has been postulated to possess anti-cancer characteristics. Gastic cell viability and stage of cell cycle were assessed using CCK8 assay and flow cytometry, respectively. Cell migration and invation were assessed using the wound healing and Transwell assays. Rate of apoptosis was determined via AV/PI-staining. Athymic nude mice xenograft models were used to evaluate the in vivo efficacy of macrocalyxin C. Western blot, luciferase experiments, cell transfection and real-time PCR allowed further study into the activation of the miR-212-3p/Sox6 pathway during macrocalyxin C treatment. We conclude that macrocalyxin C may halt the proliferation of gastric malignancies through alteration of cell invasion, apoptosis, progression through the cell cycle and cell growth. The macrocalyxin C→miR-212-3p┤Sox6 signal pathway was identified to be involved in Sox6 attenuation through augmentation of miR-212-3p values.

Potential role of microRNA-126 in the diagnosis of cancers: A systematic review and meta-analysis.

BACKGROUND: Cancer has become a major public concern all over the world and early diagnosis of cancer is of great benefit for treatment and prognosis. Several studies have investigated the association between abnormal circulating microRNA-126 (miR-126) expression and the risk of various cancers, but the results are inconsistent. Therefore, this meta-analysis was carried out to assess the potential diagnostic value of miR-126 for cancer. METHODS: Relevant studies were searched from PubMed, Embase, and Web of Science and we calculated the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operator characteristic curve (AUC) to assess the diagnostic value of miR-126 for cancer detection. RESULTS: A total of 745 cancer patients and 749 controls from 11 studies of 7 papers were included in this meta-analysis. The summary estimates revealed that the pooled sensitivity was 68% (95% confidence interval [CI]: 60-75%), the specificity was 76% (95% CI: 65-85%), the PLR was 2.87 (95% CI: 1.96-4.21), the NLR was 0.42 (95% CI: 0.35-0.52), the DOR was 7 (95% CI: 4-11), and the AUC was 0.77 (95%CI: 0.73-0.80). Moreover, the sample type, cancer type, sample size, and quality score might be sources of heterogeneity. CONCLUSION: This systematic review and meta-analysis suggests that miR-126 has great potential to be a noninvasive biomarker in the diagnosis of cancer. However, more well-designed studies with larger sample size on the diagnostic value of miR-126 for cancer are needed in the future.

FZD6, targeted by miR-21, represses gastric cancer cell proliferation and migration via activating non-canonical wnt pathway.

FZD6 plays crucial roles in human tumorigenesis. However, its mechanism in regulating cancers has not been fully elucidated. In the study, we found that FZD6 repressed gastric cancer cell proliferation and migration via activating non-canonical wnt pathway. In addition, non-canonical wnt pathway ameliorated expression of canonical wnt pathway. We also demonstrated that the FZD6 was involved in miR-21-dependent effects in the canonical and non-canonical wnt pathways in gastric cancer. These findings provide a better understanding of the development and progression of gastric cancer and may be an important implication for future therapy.

Prognostic role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 in various cancers: A meta-analysis.

Several studies have investigated the correlation between the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and cancer prognosis, with inconsistent results. Therefore, a meta-analysis was conducted to identify the potential correlation after pooling data from eligible studies. PubMed/Medline, Web of Science and The Cochrane Library electronic databases were searched for eligible studies on the prognostic role of MALAT1 in cancer, from inception to January, 2015. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to summarize the effect. A total of 1,198 patients from 10 studies were included in the analysis. The results suggested that MALAT1 expression was significantly associated with overall survival (HR=2.07, 95% CI: 1.67-2.56), disease-free survival (HR=2.60, 95% CI: 1.69-4.00) and recurrence-free survival (HR=3.28, 95% CI: 1.52-7.09). MALAT1 was also found to be significantly associated with tumor size (P=0.013). Overall, MALAT1 expression may be considered as a potential prognostic factor for cancer patients.

Potential Role of Circulating MiR-21 in the Diagnosis and Prognosis of Digestive System Cancer: A Systematic Review and Meta-Analysis.

Recent evidences indicate that circulating microRNAs (miRNAs) exhibit aberrant expression in the plasma of patients suffering from cancer compared to normal individuals, suggesting that it may be a useful noninvasion diagnostic method. MiR-21 plays crucial roles in carcinogenesis and can be served as a biomarker for the detection of various cancers. Therefore, the aim of this meta-analysis is to assess the potential role of miR-21 for digestive system cancer. By searching the PubMed, Embase, and Web of Science for publications concerning the diagnostic value of miR-21 for digestive system cancer, total of 23 publications were included in this meta-analysis. Receiver operating characteristic curves (ROC) were used to check the overall test performance. For prognostic meta-analysis, pooled hazard ratios (HRs) of circulating miR-21 for survival were calculated. Totally 23 eligible publications were included in this meta-analysis (15 articles for diagnosis and 8 articles for prognosis). For diagnostic meta-analysis, the summary estimates revealed that the pooled sensitivity and specificity were 0.76 (95% CI = 0.70-0.82) and 0.84 (95% CI = 0.78-0.89). Besides, the area under the summary ROC curve (AUC) is 0.87. For prognostic meta-analysis, the pooled HR of higher miR-21 expression in circulation was 1.94 (95% CI = 0.99-3.82, P = 0.055), which indicated higher miR-21 expression could be likely to predict poorer survival in digestive system cancer. The subgroup analysis implied the higher expression of miR-21 was correlated with worse overall survival in the Asian population in digestive system cancer (HR = 2.41, 95% CI = 1.21-4.77, P = 0.012). The current evidence suggests circulating miR-21 may be suitable to be a diagnostic and prognostic biomarker for digestive system cancer in the Asians.

Clinical role of circulating miR-223 as a novel biomarker in early diagnosis of cancer patients.

BACKGROUND: Current diagnostic procedures of cancers are invasive and non-specific. MicroRNAs (miRNAs) have become promising molecular markers for gastric cancer (GC) predication. However, there have been inconsistencies in the literature regarding the suitability of circulating miRNAs for early detection of cancers. METHODS: We performed a comprehensive meta-analysis to integrate an evaluation index for diagnostic accuracy of miR-223 in diagnosing cancer patients. Furthermore, we conducted an independent validation set of 50 gastric cancer patients and 50 healthy controls comparing miR-223 expression. We also analyzed miR-223 expression in vitro. RESULTS: A total of 11 studies met the inclusion criteria and therefore included in this meta-analysis. We found that miR-223 yielded a pooled area under ROC curve (AUC) of 0.89 (sensitivity: 81%, specificity: 84%) in discriminating cancer from controls. In our validation test, plasma miR-223 levels in GC patients were significantly higher than that in healthy controls (P<0.01). ROC curve analysis showed that AUC was 0.812 with a sensitivity of 70% and specificity of 80%. Moreover, the expression trend of miR-223 in plasma samples was in accordance with that of tissue and cell samples. CONCLUSION: Current evidences suggested that plasma miR-223 could be a reliable and non-invasive biomarker for cancer diagnosis. Further large-scale prospective studies are necessary to validate their potential applicability in human cancer diagnosis.

The Interaction Between MiR-141 and lncRNA-H19 in Regulating Cell Proliferation and Migration in Gastric Cancer.

BACKGROUND/AIMS: Non-coding RNAs including miRNA and lncRNA had been reported to regulate gene expression and were both related to cancer progression. MicroRNA-141 (miR-141) has been reported to play a role in the epithelial to mesenchymal transition (EMT) process and H19 has also been demonstrated to promote malignancy in various cancers. We aimed to determine the correlation between miR-141 and H19 and their roles in gastric cancer in this study. METHODS: H19 and miR-141 expression were detected by qRT-PCR. By bioinformatic analysis and luciferase assay we examined the correlation between H19 and miR-141 in vitro. RESULTS: H19 expression was found to be inversely correlated to miR-141 expression in gastric cancer cells and tissues. H19 promotes malignancy including proliferation and invasion whereas miR-141 suppresses malignancy in human cancer cells. MiR-141 binds to H19 in a sequence specific manner, and suppresses H19 expression and functions including proliferation and invasion. MiR-141 could also regulate H19 target genes and miR-141 inhibitor restores H19 siRNA function, while H19 regulates miR-141 target gene ZEB1. CONCLUSION: These results were the first to demonstrate that H19 and miR-141 could compete with each other and affect their target genes in gastric cancer, which provide important clues for understanding the key roles of lncRNA-miRNA functional network in cancer.

Identification of the long non-coding RNA H19 in plasma as a novel biomarker for diagnosis of gastric cancer.

Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are regarded as useful tools for cancer detection, particularly for the early stage; however, little is known about their diagnostic impact on gastric cancer (GC). We hypothesized that GC-related lncRNAs might release into the circulation during tumor initiation and could be utilized to detect and monitor GC. 8 lncRNAs which previously found to be differently expressed in GC were selected as candidate targets for subsequent circulating lncRNA assay. After validating in 20 pairs of tissues and plasma in training set, H19 was selected for further analysis in another 70 patients and 70 controls. Plasma level of H19 was significantly higher in GC patients compared with normal controls (p < 0.0001). By receiver operating characteristic curve (ROC) analysis, the area under the ROC curve (AUC) was 0.838; p < 0.001; sensitivity, 82.9%; specificity, 72.9%). Furthermore, H19 expression enabled the differentiation of early stage GC from controls with AUC of 0.877; sensitivity, 85.5%; specificity, 80.1%. Besides, plasma levels of H19 were significantly lower in postoperative samples than preoperative samples (p = 0.001). In conclusion, plasma H19 could serve as a potential biomarker for diagnosis of GC, in particular for early tumor screening.

Down-regulation of miR-203 induced by Helicobacter pylori infection promotes the proliferation and invasion of gastric cancer by targeting CASK.

Several microRNAs (miRNA) have been implicated in H. pylori related gastric cancer (GC). However, the molecular mechanism of miRNAs in GC has not been fully understood. In this study, we reported that miR-203 is significantly down-regulated in H. pylori positive tissues and cells and in tumor tissues with important functional consequences. Ectopic expression of miR-203 dramatically suppressed cell proliferation and invasion. We found that miR-203 strongly reduced the expression of CASK oncogene in GC cells. Similar to the restoring miR-203 expression, CASK down-regulation inhibited cell growth and invasion, whereas CASK over-expression rescued the suppressive effect of miR-203. These results can also be found in nude mice. In clinical specimens, CASK was over-expressed in tumors and H. pylori positive tissues and its mRNA levels were inversely correlated with miR-203 expression. Taken together, our results indicated that miR-203 functions as a growth-suppressive miRNA in H. pylori related GC, and that its suppressive effects are mediated mainly by repressing CASK expression.