The presence of Helicobacter pylori (H. pylori) infection poses a substantial risk for the development of gastric adenocarcinoma. The primary mechanism through which H. pylori exerts its bacterial ...virulence is the cytotoxin CagA. This cytotoxin has the potential to induce inter‐epithelial mesenchymal transition, proliferation, metastasis, and the acquisition of stem cell‐like properties in gastric cancer (GC) cells infected with CagA‐positive H. pylori. Cancer stem cells (CSCs) represent a distinct population of cells capable of self‐renewal and generating heterogeneous tumor cells. Despite evidence showing that CagA can induce CSCs‐like characteristics in GC cells, the precise mechanism through which CagA triggers the development of GC stem cells (GCSCs) remains uncertain. This study reveals that CagA‐positive GC cells infected with H. pylori exhibit CSCs‐like properties, such as heightened expression of CD44, a specific surface marker for CSCs, and increased ability to form tumor spheroids. Furthermore, we have observed that H. pylori activates the PI3K/Akt signaling pathway in a CagA‐dependent manner, and our findings suggest that this activation is associated with the CSCs‐like characteristics induced by H. pylori. The cytotoxin CagA, which is released during H. pylori infection, triggers the activation of the PI3K/Akt signaling pathway in a CagA‐dependent manner. Additionally, CagA inhibits the transcription of FOXO3a and relocates it from the nucleus to the cytoplasm by activating the PI3K/Akt pathway. Furthermore, the regulatory function of the Akt/FOXO3a axis in the transformation of GC cells into a stemness state was successfully demonstrated.
Background
Lymph node (LN) status is vital to evaluate the curative potential of relatively early gastric cancer (GC; T1–T2) treatment (endoscopic or surgery). Currently, there is a lack of robust ...and convenient methods to identify LN metastasis before therapeutic decision-making.
Methods
Genome-wide expression profiles of long noncoding RNA (lncRNA) in primary T1 gastric cancer data from The Cancer Genome Atlas (TCGA) was used to identify lncRNA expression signature capable of detecting LN metastasis of GC and establish a 10-lncRNA risk-prediction model based on deep learning. The performance of the lncRNA panel in diagnosing LN metastasis was evaluated both in silico and clinical validation methods. In silico validation was conducted using TCGA and Asian Cancer Research Group (ACRG) datasets. Clinical validation was performed on T1 and T2 patients, and the panel’s efficacy was compared with that of traditional tumor markers and computed tomography (CT) scans.
Results
Profiling of genome-wide RNA expression identified a panel of lncRNA to predict LN metastasis in T1 stage gastric cancer (AUC = 0.961). A 10-lncRNA risk-prediction model was then constructed, which was validated successfully in T1 and T2 datasets (TCGA, AUC = 0.852; ACRG, AUC = 0.834). Thereafter, the clinical performance of the lncRNA panel was validated in clinical cohorts (T1, AUC = 0.812; T2, AUC = 0.805; T1 + T2, AUC = 0.764). Notably, the panel demonstrated significantly better performance compared with CT and traditional tumor markers.
Conclusions
The novel 10-lncRNA could diagnose LN metastasis robustly in relatively early gastric cancer (T1–T2), with promising clinical potential.
AIM:To compare the efficacy and safety of the transthoracic and transhiatal approaches for cancer of the esophagogastric junction.METHODS:An electronic and manual search of the literature was ...conducted in PubMed,EmBase and the Cochrane Library for articles published between March1998 and January 2013.The pooled data included the following parameters:duration of surgical time,blood loss,dissected lymph nodes,hospital stay time,anastomotic leakage,pulmonary complications,cardiovascular complications,30-d hospital mortality,and long-term survival.Sensitivity analysis was performed by excluding single studies.RESULTS:Eight studies including 1155 patients with cancer of the esophagogastric junction,with 639 patients in the transthoracic group and 516 in the transhiatal group,were pooled for this study.There were no significant differences between two groups concerning surgical time,blood loss,anastomotic leakage,or cardiovascular complications.Dissected lymph nodes also showed no significant differences between two groups in randomized controlled trials(RCTs)and nonRCTs.However,we did observe a shorter hospital stay(WMD=1.92,95%CI:1.63-2.22,P<0.00001),lower30-d hospital mortality(OR=3.21,95%CI:1.13-9.12,P=0.03),and decreased pulmonary complications(OR=2.95,95%CI:1.95-4.45,P<0.00001)in the transhiatal group.For overall survival,a potential survival benefit was achieved for typeⅢtumors with the transhiatal approach.CONCLUSION:The transhiatal approach for cancers of the esophagogastric junction,especially typesⅢ,should be recommended,and its long-term outcome benefits should be further evaluated.
A novel nonenzymatic glucose sensor was successfully fabricated based on the Cu2O polyhedrons covered Cu foil. The Cu2O polyhedrons covered Cu foil was constructed via a facile, low-cost and larger ...scale producible method. The Cu2O polyhedrons covered Cu foil can be directly used as the working electrode of nonenzymatic glucose sensor, which present good stability and flexibility. The results indicated that the Cu2O polyhedrons modified Cu electrode （Cu2O/Cu electrode） showed high electrocatalytic activity for the oxidation of glucose in alkaline solution. There are two linear regions of glucose concentration for the glucose sensor based on Cu2O/Cu electrode, respectively in 10μmol/L to 0.53 mmol/L （sensitivity： 3029.33 μA （mmol/ L）^-1 cm^-2） and in 0.53-7.53 mmol/L （sensitivity： 728.67 μA （rnmol/L）^-1 cm^-2）.
A novel magnetically separable visible-light-photocatalyst, magnetite/N-doped carboxylate-rich carbon spheres （N-MCRCSs）, was synthesized by a facile ultrasonic method using the ...magnetite/carboxylate- rich carbon spheres （MCRCSs） as precursors. N element has been successfully doped into the MCRCSs in a HN03 aqueous solution via an ultrasonic treatment, which were demonstrated by the FT-IR and XPS. N- MCRCSs exhibit more intensive absorption over MCRCSs in the entire UV and visible region. N-MCRCSs can not only be easily recycled by applying an external magnetic field, but also exhibit powerful visible light photocatalytic activity.
Six rumen-cannulated lactating Guanzhong goats were used to investigate changes in ruminal fermentation pattern and the microbiota following a subacute rtmainal acidosis （SARA） inducing procedure. ...Induction of SARA was performed by increasing dietary non-fiber carbohydrate （NFC） to neutral detergent fiber （NDF） ratio from 1.02 （stage 1） to 1.24 （stage 2）, 1.63 （stage 3） and 2.58 （stage 4）. A dynamic pH monitoring system, real-time fluorescent quantitative PCR and conventional anaerobic culture were used to assess changes in ruminal pH and microbiota. Results indicated that rumen fermentation patterns changed significantly with increased NFC：NDF ratio. The decline in ruminal pH was caused by increased ruminal total volatile fatty acids （TVFA）, which was mainly attributed to a significant increase in ruminal butyrate, rather than the accumulation of ruminal lactic acid. In addition, in the course of SARA, the number of rumen microoganisms altered significantly, with increases in ruminal amylolytic bacteria, Lactobacilli, Streptococcus bovis and Megasphaera elsdenii, the latter particularly dramatically indicating that it may be the main factor responsible for the increase in butyrate, and decrease in protozoa.
Batch preparation of nano-HMX was achieved via a mechanical trituration method. The morphology and particle size of nano-HMX and raw RDX were characterized using SEM. Then nano-HMX was used in a ...formulation of composite modified double base propellant containing RDX. The method is to use nano- HMX to replace the RDX in the formulation by 10% gradually with the total mass content of RDX and HMX unchanged. The burning rate, mechanical sensitivity and mechanical property of propellant strands with different mass content of nano-HMX were tested. The results indicate that the 30% content of nano- HMX has the best comprehensive performance which can be used as an improvement of the existing formula. A possible mechanism of action was discussed.
Neuromorphic computing systems that are capable of parallel information storage and processing with high area and energy efficiencies, offer important opportunities for future storage systems and ...in‐memory computing. Here, it is shown that a carbon dots/silk protein (CDs/silk) blend can be used as a light‐tunable charge trapping medium to fabricate an electro‐photoactive transistor synapse. The synaptic device can be optically operated in volatile or nonvolatile modes, ensuring concomitant short‐term and long‐term neuroplasticity. The synaptic‐like behaviors are attributed to the photogating effect induced by trapped photogenerated electrons in the hybrid CDs/silk film which is confirmed with atomic force microscopy based electrical techniques. In addition, system‐level pattern recognition capability of the synaptic device is evaluated by a single‐layer perceptron model. The remote optical operation of neuromorphic architecture provides promising building blocks to complete bioinspired photonic computing paradigms.
An optoelectronic synaptic transistor based on a hybrid light‐tunable charge trapping medium is demonstrated. Optical programming and electrical erasing memory characteristics, along with volatile and nonvolatile memory are features of the synaptic device, enabling the mimicking of a range of neuroplasticity behaviors, including short‐term plasticity and long‐term potentiation.
Aim： To evaluate retrospectively the association of cytochrome P450 3A （CYP3A） and ATP-binding cassette sub-family B member 1 （ABCB1） gene polymorphisms with the pharmacokinetics of cyclosporine A ...（CsA） in Chinese renal transplant patients. Methods： One hundred and twenty-six renal transplant patients were recruited. Blood samples were collected, and corresponding clini- cal indices were recorded on the seventh day after the procedure. The patients were genotyped for CYP3A4＊IG, CYP3A5＊3C, ABCB1 1236 C〉T, ABCB1 2677 G〉T/A, and ABCB1 3435 C〉T polymorphisms. Whole blood trough concentrations of CsA at time zero （Co） were measured before the drug administration. A multiple regression model was developed to analyze the effects of genetic factors on the CsA dose-adjusted Co （Co/dose） based on several clinical indices. Results： The CYP3A5＊3C polymorphism influenced the Co and Co/dose of CsA, which were significantly higher in patients with the GG genotype than in patients with the AA or GA genotypes. No significant differences were detected for other SNPs （CYP3A4＊IG, ABCB1 1236 C〉T, ABCB1 2677 G〉T/A, and ABCB1 3435 C〉T）. In a univariate analysis using Pearson＇s correlation test, age, hemoglobin, blood urea nitrogen and blood creatinine levels were significantly correlated with the log-transformed CsA Co/dose. In the multiple regression model, CYP3A5＊3C, age, hemoglobin and blood creatinine level were associated with the log-transformed CsA Co/dose. Conclusion： CYP3A5＊3C correlates with the Co/dose of CsA on the seventh day after renal transplantation. The allele is a putative indi- cator for the optimal CsA dosage in the early phase of renal transplantation in the Chinese population.
A uniform monolayer of alkanethiol‐protected gold nanoparticle arrays with ultrahigh density have been used as microcontact‐printable charge‐trapping layers for the application in flexible flash ...memories. The new devices are compared to two reference devices with a floating gate created by thermal evaporation and electrostatic self‐assembly, and show a large memory window, long retention times and good endurance properties.
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